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General Anesthesia and Autonomic Nervous System: Control and Management in Neurosurgery

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Irina Alexandrovna Savvina, Anna Olegovna Petrova and Yulia Mikhailovna Zabrodskaya

Submitted: November 21st, 2021Reviewed: November 30th, 2021Published: February 8th, 2022

DOI: 10.5772/intechopen.101829

Autonomic Nervous System - Special Interest TopicsEdited by Theodoros Aslanidis

From the Edited Volume

Autonomic Nervous System - Special Interest Topics [Working Title]

Dr. Theodoros Aslanidis and M.Sc. Christos Nouris

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The chapter is devoted to the control and management of the autonomic nervous system during general anesthesia in neurosurgery. 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. We discuss the questions of the depth of anesthesia (BIS-monitoring) and antinociceptive defense, variability of heart rate (variational cardiointervalometry), hemodynamic monitoring during neurosurgical operation, intraoperative thermometry, the meaning of trigeminocardiac reflex and its classification in neurosurgery, perioperative events causing autonomic distress syndrome development and methods of its prophylaxis and treatment, pathomorphological signs of vegetative distress syndrome. Control of the neuromuscular block and photoplethysmography assessment of perfusion index (PI) as methods of the adequacy of general anesthesia and neurovegetative stability.


  • general anesthesia
  • premedication
  • autonomic nervous system
  • neurosurgery
  • brainstem autonomic centers
  • depth of anesthesia
  • trigeminocardiac reflex
  • variability of heart rate
  • autonomic distress syndrome

1. Introduction

Scientific and clinical interest in the problem of control and management of the autonomic nervous system in various fields of surgery and anesthesiology is due, in our opinion, to the relationship of the initial vegetative status of the patient (tone, reactivity of the ANS) and anesthesia techniques with the peculiarities and complications of the intra- and postoperative period; the development of cardiovascular (cardiac arrhythmias, hemodynamic instability, arterial hypertension), respiratory complications during surgery and in the early postoperative period, the occurrence of postoperative nausea and vomiting (PONV), postoperative delirium (POD), the severity of pain syndrome.

In neurosurgery, the relevance of this problem is due to the participation of autonomous control mechanisms in the autoregulation of cerebral circulation and cerebral vascular tone, which directly affects the intraoperative state of the brain, perfusion pressure of the brain, stability of its volume, and compliance—the most important characteristics reflecting the adequacy of anesthetic provision.

The literature describes prognostic predictors of complications, such as postoperative delirium, with the sympathetic pattern of the autonomic nervous system in otolaryngology surgery [1, 2], the formation of neuropathic pain and postoperative nausea and vomiting with the predominance of parasympathetic influences, etc.

Thus, it is extremely important to take into account the initial version of the tone of the autonomic nervous system. Monitoring and managing the balance and reactivity of the links of the autonomic nervous system during the preparation of the patient for surgery and during the operation and anesthesia itself will allow to obtain a result in the form of reducing the risks of perioperative complications.


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).

Figure 1.

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

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 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].

Figure 2.

Brainstem autonomic nervous centers [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].

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].

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 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 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, 24, 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, 33, 34, 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, 43, 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, 47, 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:


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. 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.

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:


The normal value for the ocular reflex is −3.95 ± 3.77. 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. 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, 50, 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, 52, 53, 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.

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].

Combination optionPremedication evening before surgeryPremedication morning on the day of surgery 30 minutes before admission to the operating room
Eutonia + normal anxiety levelNon-benzodiazepine anxiolytic (hydroxyzine) 25 mg orallyBenzodiazepine anxiolytic phenazepam (bromdihydrochlorphenylbenzodiazepine) 1 mg (1.0 ml 0.1% solution) i/m + NSAIDs (ketoprofen) 100 mg i/m
Parasympathicotonia + average anxiety levelBenzodiazepine anxiolytic phenazepam (bromdihydrochlorphenylbenzodiazepine) 1 mg (1.0 ml 0.1% solution) i/mBenzodiazepine anxiolytic phenazepam (bromdihydrochlorphenylbenzodiazepine) 1 mg (1.0 ml 0.1% solution) i/m + NSAIDs (ketoprofen) 100 mg i/m
Sympathicotonia + high anxiety levelBenzodiazepine anxiolytic phenazepam (bromdihydrochlorphenylbenzodiazepine) 1 mg (1.0 ml 0.1% solution) i/m + I1-imidazoline receptor agonist (moxonidine) 0.2 mg orallyBenzodiazepine anxiolytic phenazepam (bromdihydrochlorphenylbenzodiazepine) 1 mg (1.0 ml 0.1% solution) i/m + I1-imidazoline receptor agonist (moxonidine) 0.2 mg orally + NSAIDs (ketoprofen) 100 mg i/m

Table 1.

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

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].

Figure 4.

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


4. General anesthesia and ANS: control and management in neurosurgery

4.1 Anesthesia depth control (BIS monitoring)

The key anatomic structures of the central nervous system (CNS) that contribute to the state of consciousness are—the brain stem, the pons, the thalamus (thalamic nuclei), and the brain cortex with their connecting neural pathways [56].

General anesthetics (propofol, sevoflurane, desflurane) inhibit the excitatory arousal pathways originating in the brain stem and pons or potentiate the sleep pathways that control them [57]. The brain stem and pontine nuclei have been known to be essential in maintaining cortical arousal and forming the so-called ascending reticular formation [57].

The most important task of an anesthesiologist during neurosurgical operation is to keep anesthesia depth sufficient for security vegetative stability of the patient under the condition of general anesthesia during neurosurgical manipulations especially on the brain stem anatomic structures, cerebral arteries (clipping of cerebral aneurysm), etc. For this purpose, it is necessary to use BIS monitoring. The main component of the BIS monitor is the bispectral analysis, which evaluates the phase relations from a single-channel EEG signal measured from the patient’s forehead. The BIS index is a dimensionless number from 0 to 100. For neurosurgery, the optimal means of BIS index is around 40 so during total intravenous anesthesia (TIVA with propofol, opioid μ-agonist fentanyl) as inhalational general anesthesia (sevoflurane, desflurane). Control of the depth of TIVA during brain tumor removal (giant trigeminal schwannoma) is reflected in Figure 5.

Figure 5.

BIS-monitoring (rose line, BIS = 36) during general anesthesia (TIVA) in patient with brain tumor removal (the image is taken from the private archive of I. A. Savvina).

4.2 Intraoperative antinociceptive defense

Nociceptive stimulation during neurosurgical interventions on the brain, spine and spinal cord, peripheral nerves triggers activation of the sympathetic link of the autonomic nervous system, aseptic systemic inflammatory response [29, 34, 58]. As you know, the actual “pain” receptors are located in the skin, periosteum, and dura mater. Anticipating the development of such a scenario is possible when drugs from the NSAID group are included in the premedication scheme, in particular, ketoprofen, ketonal, lornoxicam [59]; the use of the technique of locoregional anesthesia in neurosurgery [60, 61]. There are both proponents of this approach and its opponents who associate the administration of NSAIDs in the perioperative period in neurosurgical patients with their negative effect on platelet aggregation and additional risks of postoperative hemorrhagic complications [59].

The concept of multimodal multicomponent analgesia in neurosurgical practice finds successful implementation in the form of proactive administration of NSAIDs at the stage of premedication (before the skin incision), locoregional anesthesia using naropin, at the stage of induction and maintenance of anesthesia—opioid analgesic (fentanyl) and α2-adrenergic agonist (clonidine or dexmedetomidine), when suturing a skin wound—paracetamol [53, 62, 63, 64].

On the main stage of the neurosurgical operation (brain tumor removing, cerebral aneurysm clipping, spinal hord tumor, AVM removing, etc.) antinociceptive defense is carried out with opioid analgesic μ-agonist fentanyl 3.5–5.0 mcg/kg/h + α2-adrenergic agonist clonidine 0.5 mcg/kg/h or dexmedetomidine 0.2–0.4 mcg/kg/h.

Neurovegetative stabilization with such a method and doses of drugs will be sufficient for cupping of central hemodynamic reactions during neurosurgery [65, 66, 67, 68, 69].

4.3 Hemodynamic monitoring

Hemodynamic monitoring is necessary and mandatory part of intraoperative monitoring according to Helsinki Declaration on Patient Safety in Anesthesiology (2010). Noninvasive, invasive hemodynamic monitoring, on the base of technology “PiCCO,”—all options are used in neurosurgery—arterial blood pressure systolic, diastolic, mean (BP), cardiac index (CI), stroke index (SI), global end-diastolic volume index (GEDVI), stroke volume variability (SVV), left ventricular contractility index (LVCI), total peripheral vascular resistance index (TPVRI), intrathoracic blood volume index (ITBVI), extravascular lung water index (EVLWI), pulmonary vascular permeability index (PVPI) [67, 69, 70, 71]. The choice of kind and volume of hemodynamic monitoring in neurosurgery is determined by the patient’s condition (ASA classification), operation position, localization of brain tumor, supposed blood loss, etc. The level of neurovegetative stabilization is controlled on the basis of the evaluation of the hemodynamic profile of the patient and depth of anesthesia (Figure 6) [71].

Figure 6.

Intraoperative hemodynamic monitoring during craniofacial block-resection (the image is taken from the private archive of I. A. Savvina). Non-invasive and invasive hemodynamic monitoring on the base of technology “PiCCO”: monitor PHILIPS “IntelliVue MX 800” (A); monitor PULSION Medical Systems “PiCCOplus” (B).

4.4 Monitoring of neuromuscular conduction

Monitoring of neuromuscular conduction is mandatory for neurosurgical patients for reliable and deep relaxation because the surgical manipulations on the brain structures and cerebral vessels require absolute immobility and synchronization with apparatus of artificial lung ventilation for warning of the rise of intrathoracic pressure when the scull is still closed (dura mater does not open), especially in the patients with intracranial hypertension. Remember that potentiation of neuromuscular block is possible under the condition of water-electrolytic disorders, acid-base state violations, neuromuscular diseases, hypothermia. Control of residual neuromuscular block is necessary for decision-making about the extubation of neurosurgical patients in the early postoperative period or the operating room. Musculus adductor pollicis and nervus ulnaris are the most often used for acceleromyography (registration of single twitch (ST); train of four (TOF); post-tetanic count (PTC)).

4.5 Intraoperative thermometry

Intraoperative control of central (rectal, esophageal) and peripheral (skin) temperature is necessary for timely exposure of malignant hyperthermia during inhalational general anesthesia (sevoflurane, for example) and monitoring of balance between heat products and heat dissipation in the patient under the condition of general anesthesia with or without controlled hypothermia. Also, it is necessary when the neurosurgical operation is carried out on the anatomic structures of the third ventricle of the brain and the hypothalamic zone because neurosurgery may cause immediate water-electrolyte disorders and violations of thermoregulation [42].

4.6 Variational cardiointervalometry (heart rate variability)

Variational cardiointervalometry is the noninvasive method of evaluation of the functional state of the cardiovascular system and general condition of the patients and healthy persons. The condition of the vegetative nervous system and mechanisms of regulation of heartbeat is estimated by some statistic, geometric, and special spectral characteristics including R-R intervals, HR, level HR, Baevsky tension index, the balance of the sympathetic and parasympathetic influences (LF/HF), index of centralization (IC), etc. [71, 72]. In neurosurgical patients when calculating the Kerdo index after anesthesia induction and after extubation of patients, a distinct tendency to the state of hypertension was revealed [41]. A significant decrease in heart rate variability was observed in patients with the voluminous formation in the posterior fossa with intracranial hypertension syndrome [50]. It should be noted that the perioperative results of monitoring heart rate variability were obtained using total intravenous anesthesia with the inclusion of α2-adrenergic agonist clonidine, along with dexmedetomidine, used as a component of neurovegetative stabilization in the structure of general anesthesia for neurosurgical interventions on the central nervous system [60, 65, 66, 70, 73, 74]. This method gives the possibility to estimate the prevalence of vegetative tone—sympathetic or parasympathetic or eutonia in neurosurgical patients under the condition of general anesthesia including patients with intracranial hypertension [47, 48, 49, 50].

4.7 Method of photoplethysmographic evaluation of the perfusion index

The value of perfusion index PI (N 4–5%) characterizes the volumetric peripheral arterial capillary blood flow [75]. An increase in PI is regarded as excessive perfusion as a result of redistribution of peripheral blood flow and arterioplegia. A decrease in PI values is an early and sensitive sign of adrenergic activity and peripheral vasoconstriction. This indicator is not so informative when assessing the adequacy of anesthesia during the neurosurgical intervention.

The criteria for the adequacy of anesthesiological maintenance in neurosurgery are a volume-stable, moist, pulsating, nonhyperemic brain [67, 70].

4.8 Postural circulatory reactions under general anesthesia in neurosurgery

Postural circulatory reactions under general anesthesia in neurosurgery are the most expressed when it is necessary to change horizontal position on the operating table to the operating position “sitting,” pron-position, position on the side, lounge position.

Complications associated with the surgical position during neurosurgical interventions on the posterior cranial fossa [67] are presented in Table 2.

ComplicationsSitting positionPron-positionPosition on the sideLounge position
Ventilation and perfusion complications++++
Increased pressure in the upper respiratory tract0++0+0
Tense pneumocephalus++00
Rhythm disturbances+++++++
The need for hemotransfusion++++−+
Other complications
Compression of the eyeballs0++++++
Compartment syndrome+000
Venous air embolism++++++++
Paradoxical air embolism+++??

Table 2.

Complications associated with the position during neurosurgical interventions on the posterior cranial fossa [67].

It is important to estimate the volemic status of the patient, and if the hypovolemia is obtained to start its correction with intravenous infusion of crystalloids (15 ml/kg) and colloid (5 ml/kg) solutions to avoid hypotension during seating of the patient.

4.9 Trigeminocardiac reflex in neurosurgery

The central subtype of trigeminocardiac reflex arises during intracranial impact on the nerve root, central portion of the trigeminal nerve, gasser knot when deep activation of cardiac vagus branch, and depression of lower cardiac sympathetic nerve are discovered. Usually, it is manifested by bradycardia and arterial hypotension [68, 69, 76, 77]. Figure 7 shows the giant trigeminal schwannoma (the image is taken from the private archive of I. A. Savvina). The removal of this tumor was accompanied by the central subtype of trigeminocardiac reflex (bradycardia and arterial hypertension as the variant of central TCR) [69, 77].

Figure 7.

Giant trigeminal schwannoma (shown by yellow arrow) on CT scan (the image is taken from the private archive of I. A. Savvina).

Figure 8 shows the pathways of trigeminocardiac reflex [69].

Figure 8.

Pathways of trigeminocardiac reflex [69]: (А) long ciliary nerve; (В) short ciliary nerve; (С) ciliary ganglion; (D) optic nerve; (Е) maxillary nerve; (F) winged ganglion; (G) mandibular nerve; (Н) auditory ganglion; (1) gasser knot; (2) trigeminal nerve; (3) sensor nucleus of trigeminal nerve; (4) short internuclear fibers; (5) motor nucleus of vagus; and (6) vagus.


5. Vegetative distress-syndrome and pathomorphological signs of insufficiency of ANS

The ANS performs an organizing and trophic function along with endocrine and other anatomical and physiological functional systems [78, 79]. Numerous experimental studies on the plasticity of the nervous system in various injuries of the central nervous system demonstrate the lack of specificity of changes in neurons—in the structure of the neuron nucleus appears invagination of the nuclear membrane, chromatin condensation, swelling of mitochondria, and all cisternal structures [80, 81]. These structural changes appear at any impact on the body, they are a universal ultrastructural expression of the general adaptation syndrome [78]. It is known that the structural and functional plasticity of the nerve cells is unusually high, but the appearance of morphological alterations occurs earlier and persists much longer than functional changes. Pathomorphological studies of the ANS performed on autopsy material of deceased neurosurgical patients revealed severe dystrophic and destructive changes at all levels of the ANS [82].

5.1 Afferent department of visceral reflexes

A pathomorphological study of the structures of the ANS afferent department (receptor apparatuses and sensitive nerve fibers (dendrites) that perceive and conduct afferent impulses), spinal (Th2–Th4; L1–L4; S2–S3), and similar cranial nerve ganglia (trigeminal, inferior vagus node) revealed that regardless of the nature of acute cerebral damage, there are widespread and irreversible violations of the structure and function of the components of the afferent department [28, 82].

Thus, we are talking about the partial or complete death of the sensitive nervous apparatus, the state of which largely determines the reactivity and plasticity in the implementation of an adaptive reaction. Similar changes are found not only in the intramural plexuses but also in the trunk of the vagus nerve, which carries afferent and preganglionic fibers to intramural neurons; in the posterior roots of the spinal cord, where the axons of the neurons of the sensitive spinal ganglia pass. These are nonspecific reactive changes (marginal chromatolysis with preservation of the nucleus, central chromatolysis with preservation of the nucleus, central chromatolysis with “sintering” of lumps of Nissl substance along the periphery of neurons, hyperchromatosis of the nuclei and cytoplasm of the cell in combination with edema and without it), as well as destructive irreversible phenomena (karyolysis with wrinkled hyperchromic nucleus, hydropic changes with the formation of vacuoles and karyolysis, karyorexis in combination with swelling of the neuron body). A motley kaleidoscope of changes reflects the stages of neuronal death depending on local conditions (for example, the acidity of the environment, the degree of hypoxia, hydration of the ganglion, etc.).

5.2 Central parts of the autonomic nervous system

The central parts of the ANS are associative (insertion) links of visceral reflexes. The associative link of the sympathetic nervous system is represented by the nuclei of the lateral horns of the gray matter of the spinal cord in the thoracolumbar region. During spinal cord examination at the level of Th2–Th4, Th12, and L1–L2; the insertion link of the parasympathetic nervous system at the mesencephalic (Yakubovich-Westphal-Edinger nucleus), bulbar (vegetative vagus nerve nucleus), and sacral (S2–S3) levels in the associative links, regardless of the etiological factor, widespread damage to structures and, presumably, disorders of the function of nerve cells, which are mostly irreversible, were noted [74]. Thus, we are talking about partial or significant damage to the associative link, from which the efferent vegetative pathway begins.

Neurites (axons of associative neurons) of the peripheral nerves reach the autonomic ganglia, where they end with synapses. Thanks to synapses, all the links of the visceral reflexes are interconnected and, if necessary, can act as a whole. Significant reactive changes were also revealed in the synaptic apparatus of the associative links (sympathetic and parasympathetic)—argyrophilia (affinity of synaptic rings to nitric acid silver) and hypertrophy of synapses. Destructive changes in the form of fragmentation, granular-lumpy decay of presynaptic nerve fibers, and synaptic structures formed by them on associative neurons are more pronounced in long-term critical conditions of the patient, clinical manifestations of sympathetic hyperactivity syndrome [28, 82, 83]. Nonspecific reactive changes (central and peripheral chromatolysis, acute cellular swelling, process staining, hyperchromatosis of nuclei and cytoplasm) were detected in the central parts of the sympathetic and parasympathetic nervous system. Irreversible destructive phenomena were standard (karyocytolysis, karyolysis). They reflect the different stages of neuronal death. There was also a lively glial reaction [83].

Thus, from a morphological point of view, the most dramatic situation develops in the associative link of the sympathetic nervous system.

The death of neurons nuclei in all parts of the hypothalamus (large-cell nucleus of the anterior hypothalamus, small-cell nuclei of the middle hypothalamus, nuclei, and pathways of the posterior) was also noted [83].

5.3 Efferent section of the visceral reflexes

The efferent autonomic pathway is represented by neurites of associative neurons (preganglionic fibers) and effector neurons and their neurites (postganglionic fibers). The latter reach the innervated tissues, where they realize their impact. The studied sympathetic ganglia (cervical-thoracic or stellate, 2nd–6th thoracic paravertebral, abdominal plexus) are connected by preganglionic fibers with sympathetic centers of the spinal cord; parasympathetic ciliary node—with the Yakubovich-Westphal-Edinger nucleus; Auerbach and Meissner plexuses—with the autonomic nucleus of the vagus nerve.

In acute cerebral injury, extensive structural and functional disorders of the main components of the autonomic ganglion—neurocytes are revealed; at the same time, the “management” of special functions of some organs (glands, smooth muscles of internal organs and vessels, heart muscle, ciliary and pupillary muscles, etc.) and the general adaptive and trophic function suffer [83]. A motley pattern of reactive changes is observed in the sympathetic ganglia—central and peripheral chromatolysis, total chromatolysis with preservation of the nucleus and nucleolus and “sintering” of chromatophilic substance along the edge of the neuron body, hyperchromatosis of the nucleus and perinuclear edema, wrinkling of nuclear material into a homogeneous structureless mass with total chromatolysis (Figure 9).

Figure 9.

Sympathetic ganglion 3 days after severe traumatic brain injury (column intermediolateral medullae spinalis). (A) Argyrophilia, hypertrophy, deformation of synapses on neurons. Impregnation by Kahal. Magnification X 100. (B) Destructive changes in the synaptic vesicle. Electronogram. Magnification X 1800.

Reactive changes in the parasympathetic ganglia were nonspecific—destructive changes were standard (karyolysis, karyocytolysis), a pronounced reaction from the glia was noted in the ganglia (the number of glial cells (satellites) closely adjacent to the perikaryon of the neurocyte and penetrating it increased around the neurocytes).

The last link of the visceral reflexes is postganglionic fibers, which, as part of nerve trunks and bundles, penetrate all organs and tissues of the body, where they form effector nerve endings. The efferent section of the visceral reflex arches also detects gross dystrophic changes.

The duration of the patient’s stay in critical condition correlates with the number of damaged and dead neurons—the longer the period, the more widespread the damage to the ANS was. The death of neurons and their processes can also be caused by their functional overload, excessive functional stress, malfunctions in the rhythm of work, etc.

Some patients who have suffered severe critical conditions recover and return to life with a deeply disabled ANS with a sharply narrowed range of adaptive reactions [28].

Death can occur from the disintegration of the organism as a system with the relative safety of the components of the system (organs) with far from exhausted reserves [83].

Thus, the totality of dystrophic and necrobiotic changes detected in the ANS is the morphological equivalent of vegetative distress syndrome and ANS insufficiency.


6. Conclusion

To summarize, it is obvious that the autonomic nervous system is one of the main systems of life support. Control and monitoring of its functional activity is especially important when the patient is under the condition of general anesthesia. Neurosurgery causes specific central hemodynamic reactions related to reflexes from the brainstem. Management of autonomic reactions and vegetative tone are possible with neurovegetative stabilization and control of the depth of anesthesia.


Conflict of interest

The authors declare no conflict of interest.


Notes/thanks/other declarations

We would like to thank our parents who supported us when we chose medicine as profession and taught us mercy and compassion.



ANSautonomic nervous system
CNScentral nervous system
NSAIDsnonsteroid anti-inflammatory drugs
PОNVpostoperative nausea and vomiting
PОDpostoperative delirium
PIperfusion index
TCRtrigeminocardiac reflex
VASvisual-analog scale of pain


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Written By

Irina Alexandrovna Savvina, Anna Olegovna Petrova and Yulia Mikhailovna Zabrodskaya

Submitted: November 21st, 2021Reviewed: November 30th, 2021Published: February 8th, 2022