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EVALUATION OF THE INFLUENCE OF COMBINATIONS OF DRUGS FOR GENERAL ANESTHESIA ON CHANGE OF ACTIVITY OF STRESS-LIMITING AND STRESS-REALIZING LINKS ON THE CLINICAL MODEL OF ACUTE STRESS DAMAGE

Introduction: When a person is in a state of anesthesia - sedation, the realization of the stress reaction is carried out through the mesocortical - limbic system, while performing intensive therapy outside sedation - through the amygdala and the hippocampus. In this regard, the response of the stress system under anesthesia and outside it will be different and, consequently, the evaluation of reactions during anesthesia is extremely interesting and necessary for targeted (individual) choice of combinations of drugs for anesthesia, depending on their effect on the links of the stress system. The more interesting is the response of the stress system in the conditions of the existing pathology, which in itself is accompanied by a stressful response.

Objectives: Evaluation of the reaction of the stress system (with the identification of age-specific features), determining the response characteristics of the stress-realizing and stress-limiting links, determining the total response of the stress system, depending on the combination of drugs used for general anesthesia on the clinical model of general surgical acute stress (adults and children).

Methods: Multicentre open clinical trial (2003-2015). This article presents the data of the group without the syndrome of intracranial hypertension (WSICH) - a general surgical group: 78 adults and 87 children. The group without SICH was interesting, as a group of "typical response" to stress in the form of trauma, emotional stress, pain factor. Two types of total intravenous anesthesia were used: standard (SA) - fentanyl, propofol and modified (MA) - fentanyl, propofol, ketamine, sodium oxybate. The markers of activity of the stress system (cortisol, corticotropic releasing factor (CTRF), β-endorphin, serotonin, histamine) were studied, the concentrations of interleukins in the blood serum (IL-4, IL-6, TNFa, IL-lß, IL-2). The study was conducted in the preoperative period and on the 5th-7th day after the operation. Statistical processing of the results was carried out.

Results and discussion: The normal initial reaction of the stress-realizing-link (SR) of the stress system was determined (the normal stress-typical stress response in adults and children) on preoperative (psycho-emotional) and pain (traumatic) stress, which is expressed in: normal level of cortisol (adrenal level); normal level of CTRF (hypothalamic level); increased level of histamine; The normal level of IL1; normal level of IL6; increased IL2; decrease in the level of TNFα. The normal initial reaction of the stress-limiting-link (SL) of the stress system is determined which is expressed in: normal serotonin level in children and increase in 30% of adults (a typical pathophysiological reaction associated with age, which demonstrates the "vulnerability" of the SL link in adults); Reduction of β-endorphin level (a discussion on the need to enhance opioid exposure in order to prevent inadequate anesthesia); An increase in IL4 mean values. The typical reaction of the SR and SL - stress system links to the surgical intervention (surgical stress) using standard (group SA) and modified (group MA) variants of TIA was revealed. For the SR-link, increased cortisol levels, increased CTRF level, normalization of histamine level, normalization of IL1 indices, a decrease in IL6 level, an increased level of IL2, an increase in the level of TNFα. For the SL-link, serotonin level was decreased (decrease of the SL potential and the need for additional activation via NMDA receptors), increased β-endorphin level (adequacy of opioid stimulation of the SL-link), an increase in IL4 in 75% of adults and 80% of children Need for additional stimulation via GABA receptors).

Conclusions: The "norm of pathology" (or "stress-norm") of the reaction of the SL-link (activation of stress-limitation), which can be estimated as normal when it is identical to the stimulation of the SR-link, for leveling the destabilizing influence of SR-stimulation, that is, Vegetative stabilization is achieved. In contrast to the SR-link, the possibility of combinations of drugs for general anesthesia to the activity of the SL-link receptors was revealed, the "point of application" for drugs was shown, with the prospect of developing techniques (new combinations) that could affect serotonin metabolism in the brain. It is possible to introduce a new concept - stress-limiting anesthesia, which is necessary, due to the received data that "depth of anesthesia" and "adequacy of anesthesia" are not identical concepts. Preparations for general anesthesia affect, first of all, the activity of the SL-link of the stress system and it is due to their combinations based on the initial activity of the stress system that it is possible to achieve adequate stress-limiting anesthesia.

Иллюстрации

Table 1. Separation of patients by subgroup (anesthetic components) in study groups

Note: * – (1 – standard anesthesia, 2 – modified anesthesia).

Fig. 1. The multiplicity of the excess of the stress-activating link of the stress system in adults and children (a – adults, b – children)

Fig. 2. Changes in the stress-activating link in adult patients of the general surgical profile (a – after surgery, standard anesthesia, b – after surgery, modified anesthesia, where 1 – average values of normal indicators)

 Fig. 3. Change in the indicators of stress-activating link in children of general surgical profile (a – after surgery, standard anesthesia, b – after surgery, modified anesthesia, where 1 – average values of normal indices)

Fig. 4. The total typical evaluation of the reaction of the stress-activating -link of stress system («pathology norm») in adults and children in the preoperative period and after standard and modified anesthesia, where the indicators within the limits of the norm are taken as 1, the excess of the indicator (times deviations from the norm) – «+2, +4, etc.», decrease in the indicator (times by deviations from the norm) – «-2, -4, etc.», the value of the indicator, which has up to 50% of the results within the norm, And the remaining increase is «+0,5», the value of the indicator, which has up to 50% of the results of the decrease from the norm – «-0,5».

Fig. 5. Multiplicity of excessing indicators of the stress-limiting link of the stress system in adults and children (a – adults, b – children)

Fig. 6. Changes in the indicators of stress-limiting link in adult patients of general surgical profile (a – after surgery, standard anesthesia, b – after surgery, modified anesthesia, where 1 – average values of normal indices).

 Fig. 7. Changes in the stress-limiting link in children of the general surgical profile (a – after surgery, standard anesthesia, b – after surgery, modified anesthesia, where 1 – mean values of normal indicators)

Fig. 8. The total typical evaluation of the response of the SL-link of the stress system (the «pathology norm») in adults and children in the preoperative period and after standard and modified anesthesia, where the parameters within the limits of the norm were taken as 1, the excess of the indicator (times deviations from the norm) – «+2, +4, etc.», decrease in the indicator (times by deviations from the norm) – «-2, -4, etc.», the value of the indicator, which has up to 50% of the results within the norm, And the remaining increase is «+0,5», the value of the indicator, which has up to 50% of the results of the decrease from the norm – «-0,5».

Fig. 9. The total typical evaluation of the reaction of the stress system in adults and children (the «pathology norm» or «stress norm») in the pre- and postoperative periods (SA and MA), where the indices within the norm are taken as 1, – deviation from the norm) – «+2, +4, etc.», decrease in the indicator (times by deviations from the norm) – «-2, -4, etc.», the value of the indicator, which has up to 50% Results within the limits of the norm, and the remaining increase is «+0,5», the value of the indicator, which has up to 50% of the results of the decrease from the norm – «-0,5».

DOI: 10.18413/2313-8971-2017-3-3-71-88
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