**2. The brain and the autonomic nervous system**

## **2.1 The structure of the sympathetic and parasympathetic links of the autonomic nervous system**

The leading role in maintaining the constancy of the internal environment of the body is played by the department of the nervous system, which regulates the activity of internal organs, glands of internal and external secretion, blood, and lymphatic vessels—the autonomic nervous system.

Autonomic neurons are located mainly in the spinal cord—sympathetic in the thoracic region, parasympathetic in the sacral region (**Figure 1A** and **B**).

### *2.1.1 Segmental division of the autonomic nervous system*

Segmental parts are also embedded in the brain stem—the nuclear apparatus of the vagus nerve; the vegetative nucleus of the VII nerve, the fibers to the sublingual and submandibular glands and the vessels of the meninges; the vegetative nucleus of the IX nerve, from which the tympanic nerve begins, going to the parotid gland, and the

### **Figure 1.**

*The structure of the sympathetic (A) and parasympathetic (B) links of the autonomic nervous system.*

*General Anesthesia and Autonomic Nervous System: Control and Management in Neurosurgery DOI: http://dx.doi.org/10.5772/intechopen.101829*

vegetative nucleus of the oculomotor nerve (Yakubovich-Edinger-Westphal nucleus), the fibers of which are involved in the regulation of pupil size (**Figure 2**) [3, 4].

The number of neurons included in segmental devices exceeds the number of neurons in the brain [5]. Stem nuclear formations are homologs of the lateral horns of the spinal cord, as well as motor and sensory nuclei of the brain stem are homologs of the anterior and posterior horns.

### *2.1.2 Suprasegmental vegetative nervous system*

This integrative system combines the reticular formation of the brain stem, hypothalamus, thalamus, amygdala, hippocampus, septum, together with their connecting paths, which form a functional system, called the limbic-reticular complex (**Figure 3**) [4].

The limbic system provides the integration of somatic and vegetative nervous system—regulation of the autonomic, hormonal functions that provide various forms of activity, including in conditions of general anesthesia and surgical exposure [6, 7].

### **2.2 Cerebral blood flow and autonomic nervous system**

Both parts of the ANS—sympathetic and parasympathetic—are actively involved in the regulation of cerebral vascular tone and blood supply to the brain [8]. The leading role in the sympathetic innervation of cerebral vessels is played by the upper cervical and stellate ganglia. The proximal 2/3 of the basilar artery and vertebral arteries are innervated by the superior cervical ganglion. The anterior, middle, and posterior arteries receive nerve fibers from ganglion cells of the trigeminal ganglion [9].

The sympathetic nervous system participates in protecting the microcirculation of the brain from hemodynamic overloads and thereby preserves the blood-brain barrier and protects brain tissue during significant increases in systemic blood pressure in extreme situations [5, 8, 10]. It is assumed that the trigger for autoregulation

**Figure 3.**

*Limbic system of the brain. Sagittal section through the brain hemispheres (a). Medial view from the right hemisphere of the brain (b). Enlarged image of the limbic system (c) [4].*

of excessive narrowing of the cerebral arteries is reflexes from the baroreceptors of the aorta, carotid sinuses, and dura mater, which are realized through the sympathetic nervous system [11]. In response to the stimulation of these receptors, central impulses arise, traveling along the sensitive fibers of the IX and X pairs of cranial nerves to the nucleus of a single pathway located in the medulla oblongata. After processing these signals via efferent pathways, information reaches the executive organs—the heart, blood vessels, kidneys, adrenal glands, and also through the participation of neuroregulatory systems, an integrative response of the brain is triggered in the mechanisms of autoregulation of cerebral circulation [8].

Stimulation of parasympathetic nerves increases cerebral blood flow. The mechanisms of vasodilation of brain vessels during activation of the parasympathetic nervous system are not specified. It is assumed that under the influence of acetylcholine, the content of cyclic guanosine monophosphate (cGMP) increases and the activity of cGMP-dependent protein kinase increases. It is also possible that under the influence of acetylcholine released in synapses, the exchange of potassium and sodium ions changes, and sodium-potassium ATPase is also involved [12]. The large arteries of the base of the brain are innervated by serotonin-containing fibers of sympathetic origin. To date, it has been established that constriction or dilation of blood vessels under the influence of serotonin is caused both by direct action on smooth muscle cells of cerebral vessels, and indirectly through activation of serotonin receptors (HT1, HT2) on perivascular nerve terminals or vascular endothelial cells [13, 14].

## **2.3 Mechanisms for the implementation of stress reactions with the participation of autonomous regulation centers**

The stress reactions are based on activation and tension of the hypothalamic-pituitary-adrenal system and the adrenergic system [15, 16], then an increased synthesis

*General Anesthesia and Autonomic Nervous System: Control and Management in Neurosurgery DOI: http://dx.doi.org/10.5772/intechopen.101829*

of glucocorticoids and the release of catecholamines in the blood and target organs is triggered [17]. The hippocampus has an inhibitory effect on the neurosecretory system of the hypothalamus and protects it from excessive stress [18]. The hippocampus is also able to inhibit adrenocortical activity and, thus, influence the duration and dynamics of the stress reaction [19, 20]. It is known that emotional stress triggers a powerful stimulation of sympathetic arousals [21, 22], then there is a decrease in the sympathetic and secretory activity of the adrenal glands [23–25], and the body moves to a different metabolic level with the formation of stress resistance [26, 27].

An imbalance of the links of the autonomic nervous system can lead to the development of autonomic distress syndrome in the perioperative period [5, 28, 29].

### **2.4 Surgical stress and central mechanisms of stress response realization**

It is proved that various neurotransmitter systems of the brain are involved in the reactions of the central nervous system to surgical stress—the adrenergic, dopaminergic, cholinergic system since pathological reflexes from the surgical wound are realized through the vagal nuclear complex in the form of vegetovisceral efferent responses [12]. A hypermetabolic state causes [30, 31] the need for tissues for oxygen increases, and the activity of the cardiovascular system increases [15, 32–35]. It is proved that the intensity of reactions of the links of the hypothalamic-pituitary-cortical-adrenal system depends on the type of stress factor and the initial functional state of this system [36, 37]. Arteriole spasm leads to an increase in total vascular resistance, microcirculatory and rheological disorders, the consequence of these pathophysiological changes will be a redistribution of the volume of circulating blood, hypovolemia, tissue and organ ischemia and hypoperfusion, violations of acid-base and water-electrolyte balance, increased peroxidation reactions [38]. Surgical stress causes changes in the permeability of cell membranes, their ultrastructural damage, which will result in a decrease in the functional reserves of organs [36]. The result of surgical stress will be the development of multiple organ dysfunction with the progression of cardiovascular, respiratory failure; impaired liver, kidney, gastrointestinal tract, immunological reactivity, and regulation of the aggregate state of blood in the form of hypercoagulation [29, 39].

## **3. The role of the autonomic nervous system in limiting stress reactions under conditions of neurosurgical influence**

The autonomic nervous system has a modulating effect on compensation mechanisms and their adequacy in response to surgical trauma [40]. The brainstem and supratentorial cerebral centers of autonomic regulation are the most important structures for control and management during general anesthesia using pharmacological defense with α2-adrenergic agonists and opioid analgesics. Daily monitoring of heart rate variability in neurosurgical patients, along with the calculation of the autonomic Kerdo index, in the early postoperative period showed distinct eutonia after removal of a brain tumor under general anesthesia with the opioid analgesic fentanyl in combination with the α2-adrenergic agonist clonidine [41]. Dysfunction of the autonomic nervous system can lead to disruption of adaptation in response to surgical intervention, the development of severe hemodynamic reactions, and complications of the early postoperative period [28, 42–44].

### **3.1 Assessment of the functional state of the autonomic nervous system in neurosurgical patients**

To assess the vegetative status of neurological patients, some authors have proposed generalizing methods [6, 45]. To assess the state of the autonomic nervous system in the perioperative period, some authors used indicators such as the autonomic Kerdo index, a study of daily heart rate variability and their mathematical models, including in patients with intracranial hypertension [46–48].

### *3.1.1 Assessment of the type of vegetative tone*

The Kerdo index is the "gold standard" for assessing the type of vegetative tone. When studying the ratio of diastolic pressure and the number of pulse beats per minute, it was suggested that changes in the ratio of diastolic pressure and the number of pulse beats are associated with shifts in vegetative tone.

The calculation of the vegetative Kerdo index is carried out according to the formula:

$$\mathcal{VI} = (\mathbf{1} - \mathbf{D} / HR) \times \mathbf{100} \tag{1}$$

where VI is the vegetative index, D is the value of diastolic pressure; HR is the heart rate in 1 minute.

Interpretation of the results—complete vegetative equilibrium (eutonia)— VI = 0 − +7; sympathotonia—VI > +7; parasympathotonia—VI < +7 and negative values.

The evaluation of the indicator in dynamics allows us to trace the degree of stress and drug effects on the tone of the ANS.

The interpretation of the calculated values assumes that the minute volume (MV) of the heart with sympathotonia is greater than in a calm state with parasympathotonia. In turn, MV is associated with the compensation of the circulating blood volume (CBV) by peripheral resistance within physiological boundaries. It can be assumed that fluctuations in the minute volume are approximately expressed in terms of pulse rate, and changes in peripheral resistance are expressed through diastolic pressure. This explains the fact that with sympathotonia the pulse rate increases and the diastolic pressure decreases; with parasympathotonia the pulse rate decreases and the diastolic pressure increases. This implies a decrease or increase in the vegetative index toward negative or positive values.

### *3.1.2 Assessment of vegetative reactivity*

The assessment of vegetative reactivity in our study was carried out using the Dagnini-Aschner test and the Cermak-Goering sinocarotide reflex.

### *3.1.2.1 The ocular reflex (Danyini-Ashner)*

The test was carried out as follows—after 15 minutes of lying at rest, the patient's heart rate is calculated for 1 minute (baseline background). Then the pads of the fingers are pressed on both eyeballs until a slight pain appears. After 15–25 seconds, the heart rate is recorded for 20 seconds.

Normally, after a few seconds from the beginning of the pressure, the heart rate slows down by 6–12 beats per 1 minute.

*General Anesthesia and Autonomic Nervous System: Control and Management in Neurosurgery DOI: http://dx.doi.org/10.5772/intechopen.101829*

With a normal slowing of the heart rate, normal vegetative reactivity is noted; with a strong slowdown (parasympathetic, vagal reaction)—increased vegetative reactivity; with a weak slowdown—decreased vegetative reactivity; in the absence of slowing—perverted vegetative reactivity (sympathetic reaction).

Due to the different initial heart rates (more or less than 70–72 beats per 1 minute), it is possible to calculate according to the Galu formula:

where HRS is the heart rate in the sample; HRI is the initial heart rate.

The slowing down of the pulse according to the Galu formula is equal to:

$$\text{XX} = \mathbf{100} \* HR\mathbf{S} / HRI \tag{2}$$

The normal value for the ocular reflex is −3.95 ± 3.77.

### *3.1.2.2 Evaluation of the Cermak - Goering sinocarotid reflex*

The technique of the test—after a 15-minute adaptation (rest) in the supine position, the heart rate is calculated in 1 minute—the initial background. Then alternately (after 1.5–2 seconds), the fingers (index and thumb) are pressed on the area of the upper third of the m. sternocleidomastoideus slightly below the angle of the lower jaw until the carotid artery pulsates. It is recommended to start the pressure from the right side since the effect of irritation on the right is stronger than on the left. The pressure should be light, not causing pain, for 15–20 seconds. From the 15th second, the heart rate begins to register for 10–15 seconds. Then the pressure is stopped and the heart rate is calculated in a minute. It is also possible to register the state of the after effect at the 3rd and 5th minutes after the cessation of pressure. Sometimes blood pressure and respiratory rate are recorded.

Interpretation—the values obtained in healthy subjects, that normal vegetative reactivity, are taken as a normal change in heart rate. The normal value of M ± a for the synocarotide reflex is 4.9 ± 2.69.

Values above normal indicate increased vegetative reactivity, that is increased parasympathetic or lack of sympathetic activity, lower—a decrease in vegetative reactivity. An increase in heart rate indicates a perverse reaction.

### *3.1.2.3 The study of the functions of the segmental part of the autonomic nervous system*

The study of the functions of the segmental part of the autonomic nervous system is carried out by conducting an orthostatic test.

The state of the sympathetic efferent pathway is determined according to changes in blood pressure associated with the transition to the vertical position of the patient. The difference in systolic blood pressure is calculated in the supine position and at the 3rd minute after the patient gets up.

Interpretation—a decrease in systolic blood pressure by less than 10 mm Hg is a normal reaction indicating the integrity of efferent vasoconstrictor fibers; a decrease by 11–29 mm Hg is a borderline reaction; a drop by 30 mm Hg and more is a pathological reaction indicating efferent sympathetic insufficiency.

The state of the parasympathetic efferent pathway is determined by measuring the heart rate when getting up. In healthy people, the heart rate increases rapidly when getting up (the maximum figure is noted after the 15th heartbeat) and then decreases

after the 30th heartbeat. Normally, the quotient of the division of the first value to the second should be equal to 1.04 or more; 1.01–1.03—borderline result; 1.00—insufficiency of vagal influences on the heart.

### **3.2 Localization of the brain tumor and vegetative status**

The results obtained in the neurosurgical clinic allowed us to conclude that when the tumor was localized in the middle and posterior cranial fossa, there was a predominance of activity of the parasympathetic link of the nervous system [41]. Dysfunction of stem structures in the posterior cranial fossa, irritation of the brain stem due to tumor growth with irritation of the nuclei of the caudal group of cranial nerves, in patients with a tumor of the IV ventricle—nuclei and formations of the rhomboid fossa, vagal nuclear complex can serve as an explanation for the predominance of the parasympathetic tone of the ANS in patients with a tumor of supratentorial localization.

A few studies were devoted to the analysis of the vegetative status of neurosurgical patients in the perioperative period [41, 44, 49–51]. It was found that the localization of the brain tumor had a significant effect on the vegetative status [51]. Thus, with supratentorial localization of the tumor in the temporal lobe, patients had sympathicotonia with an average level of the personal and high level of situational anxiety. This can be explained both by the direct involvement in the pathological tumor process of the structures of the mediobasal parts of the temporal lobes (amygdala, hippocampus) according to the neuroimaging data presented in the medical history and by indirect irritation of the brain structures forming the limbic system of the brain. In patients with frontal lobe tumors, there was a predominance of sympathicotonia with a high level of personal and an average level of situational anxiety on the eve of surgery. It is known that central noradrenergic systems (in particular, the structures of the brainstem—locus coeruleus) play a significant role in the occurrence of vegetative disorders with pronounced anxiety and fear. Through the ascending pathways, this zone has a connection with both the hypothalamic-pituitary system and the structures of the limbic-reticular complex (hippocampus, amygdala, frontal cortex). Through the descending pathways, noradrenergic structures are connected to the peripheral parts of the sympathetic nervous system. Irritation of the frontal lobes due to tumor growth probably explains the activation of the sympathetic link of the ANS in this category of patients.

### **3.3 Assessment of the vegetative and psycho-emotional status of neurosurgical patients before operation**

The inclusion in the preoperative examination of an anesthesiologist of methods of functional and dynamic examination of the autonomic nervous system to determine the tone of the sympathetic and parasympathetic links of the autonomic nervous system before surgical treatment and assessment of psycho-emotional status [31, 51–54] in elective neurosurgical patients, pain syndrome assessment with the help of VAS of pain allows the anesthesiologist to prescribe an individual premedication to create a vegetative-stabilizing effect, anxiolysis, reducing the afferent flow of information to the brain to create a functional rest of the central nervous system before surgery.

The result of effective premedication will be a smooth induction of anesthesia and a satisfactory intraoperative state of the brain.


 *Premedication schemes for elective neurosurgical patients depending on the level of personal anxiety and the initial tone of the VNS links.*

*General Anesthesia and Autonomic Nervous System: Control and Management in Neurosurgery DOI: http://dx.doi.org/10.5772/intechopen.101829*

**Figure 4.** *RVLM and central adrenergic and imidazoline 1-receptors location [55].*

Recommended premedication schemes for elective neurosurgical patients, depending on the level of personal anxiety and the initial tone of the ANS links, are presented in **Table 1** [51].

According to modern concepts, the therapy of hyperactivity of the sympathetic nervous system is carried out by influencing the centers that control the work of the cardiovascular system and are located in the brain stem, the most important of which, apparently, is the rostral-ventrolateral region of the medulla oblongata (RVLM) [55]. Various types of receptors are located in this zone, including α2-adrenergic receptors and imidazoline receptors (**Figure 4**) [55]. It has been shown that imidazoline receptors of subtype 1 (I1) located in RVLM take an active part in blood pressure control, exerting a significant regulatory effect on the activity of the sympathetic nervous system [55].
