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0MEDICAL SCIENCES
TOXICOLOGICAL RISKS IN THE TECHNOLOGY OF INHALATION ANESTHESIA AND RESPIRATORY SUPPORT PROBLEMS
Salekh E.N.
Odessa National Medical University, Department of Anaesthesiology, Intensive Care with Postgraduate
Education, Odessa; Cand. Med. Sci., Docent
Shafran L.M.
State Enterprise Ukrainian Research Institute for Medicine of Transport, Odessa, Ukraine; First Vice-Director, Director of Hygiene and Toxicology Department; Dr. Med. Sci., Prof.
Abstract
BACKGROUND:
Surgical trauma is a leading etiological factor of surgical stress, which forms the state and subsequent development of the systemic post-aggressive response of the patient. Surgical stress is an acute disturbance of metabolism, physiological functions and psychological status of the organism under the influence of preparatory procedures, surgical intervention and recovery factors. Anesthesia provides a set of measures aimed at protecting the patient's body from the damaging effect of surgical injury. In the course of his professional work, the anaesthetist is in the narrow corridor between the therapeutic effect of anesthetic and its toxicity. However, the mechanisms of the latter remain insufficiently studied. A generalization of the separate literature data and the choice of the direction of further research was the purpose of this study.
RESULTS:
The basic hazard of the development of possible toxic effects is the very nature of the structure and the physical and chemical properties of the drug substance, related to narcotic drugs - neurotoxicants. Under certain circumstances (psycho-somatic state of the patient, age, concomitant diseases), chemical hazard can be realized not only as a result of overdose or inadequate combination of drugs, but also by an altered character of the organism's response. To provide a multicomponent general anesthesia in modern anesthesiology, inhalation and intravenous anesthetics, hypnotics, a number of other drugs that increase the chemical load on the patient's body are used. The effect of inhalation anesthetics on the respiratory system, in the absence of adequate respiratory support, the synergy of the combined processes of oxidative stress, hypoxia and dysregulatory disorders are the basis of neurotoxic effects as a pathogenetic basis of the chemical hazard of anesthetics.
CONCLUSIONS:
Ensuring the chemical safety of the patient at the stages of preparation, surgery and recovery is an urgent problem, the solution of which dictates the need for complex clinical and experimental studies aimed at establishing regularities, studying the mechanisms of development of toxic effects of anesthetics and metabolic products covering all main links of the functional system from the molecular, cellular to the organism as a whole, with the obligatory recording individual-personal specific features and psychological status of the patient.
Keywords: inhalation anesthetics, chemical hazards, toxicity mechanisms, oxidative stress, hypoxia, neuro-toxicity, respiratory support.
Acute damage and surgical trauma are the leading etiological factors of surgical stress that form the state and subsequent development of the systemic post-aggressive response of the patient [12, 27]. In surgical interventions, a number of factors (pain, blood loss, mechanical trauma) that cause disharmony of all body functions, which have been negatively affected by the underlying disease, are acting on the body. The very expectation of surgical intervention contributes to an increase in the release of hormones of the brain substance and the adrenal cortex 2 to 4 times, resulting in increased rate of formation of active forms of oxygen, hydroperoxides of lipids and other patterns of oxidative and psychoemotional stress [7,28,33].
Surgical stress is an acute disturbance of metabolism, physiological functions and psychological status of the organism under the influence of preparatory procedures, surgical intervention and factors of the recovery period [3,42]. At the same time, stress is also a powerful adaptive mechanism. While increasing the level of cellular metabolism, contributing to the mobilization
of body reserves of the patient, surgical stress facilitates the course of the perioperative period [14]. However, intensive and prolonged activation of the body's defensive systems - nervous, hormonal, immune, leads to depletion of adaptive reserves [40].
Anesthesiologic support of surgical intervention is one of the most important problems of clinical surgery; it includes a set of measures aimed at protecting the patient's body from the damaging effects of surgical trauma and minimizing psychoemotional stress. Surgical trauma leads to a reorganization of the circulation, and the more serious it is, the higher are the risks of anesthesia, which include the potential general toxic effects of anesthetic drugs and local anesthetic systemic toxicity (LAST) [11,13,18]. As shown in the experimental study of S.E. Copeland et al. [9], general anesthesia had a significant effect on the content, excretion and clearance of R-bupivacaine> S-bupivacaine and R-prilocaine> S-prilocaine in the heart and brain (mepi-vacaine influenced insignificantly, and halothane had
The scientific heritage No 18 (18),2017 no significant effect). Since the effect of local anesthetics is of polytrophic character blocking Na-channels in the sensory nerve fibers as well as a wide range of cell membranes. This must be taken into account when predicting the combined effects of not only general and local anesthetics, but also of other medications with a similar type of therapeutic effect used in surgical practice. Moreover, in recent years the spectrum of target receptors of toxicogenic effects of LAST has significantly expanded. This list includes such functional membrane proteins as acetylcholine and adrenergic receptors, y-aminobutyric acid, potassium and calcium channels as well as membrane enzymes such as adenyl-ate cyclase, phospholipase A2 and Na, K-ATPase [6,35,39]. This can determine cardiorespiratory effects, which correspond to the action of inhaled drugs [39]. Progress in studying the mechanisms of such dangerous interactions has allowed to make significant progress in the development and application of antidotes (in particular, lipid emulsions), which is in satisfactory correspondence with the lipotropy of the drugs in question [21, 43].
The implementation of toxicological risks can be traced at all levels of socio-biological organization of the functional systems, and the most pronounced manifestations take place at the molecular, cellular and sub-cellular level (energy and biosynthetic components) as well as at the organism level - as restruction of regulatory and integrative higher mental functions (physiological and psychological components). In the process of surgical intervention and, especially, in the postoperative period, the contribution of the latter to the recovery processes increases substantially. Thus, S. Pa-rekh et al. [30], Prakash R. et al. [32] showed that in groups of patients with a surgical profile, practically regardless of the type of ratio of general and local anesthetics used in the course of operative intervention, pain syndrome, anxiety and distress predominated in the postoperative period. Given the probability of toxic effects in virtually all drugs used for anesthesia, the anesthetist, in the course of his professional activities, is in the narrow corridor between the therapeutic effect of the anesthetic and its toxicity, and faces manifestations of a specific and nonspecific response of the organism to the drug used [7,18,27]. The main danger of possible toxic effects lies in the very nature, structure and phys-icochemical properties of the drug substances, which are related to narcotic drugs - neurotoxicants [4,38,41].
Toxicological risk in anesthesia is associated with a number of predisposing factors: the underlying disease, the presence of concomitant pathology and associated pharmacological anamnesis of the patient, the type and technology of surgical intervention on which the choice of the method of anesthesia depends [24, 25]. In a number of cases, there is a need to maintain, and sometimes also to renew the function of vital organs with the use of various additional infusion means and medicines, which together with anesthetics can have a combined effect on the body. In this case, the nature of the combined action submits to the general regularities established in experimental and clinical studies for different categories of xenobiotics [20,31,37]. The heavier the patient's condition, the severer the pathology, the
more massive is the chemical "aggression", which is aimed at helping the patient, but at the same time exposes the patient's body to chemical hazards.
To conduct general anesthesia in modern anesthe-siology, intravenous anesthetics and hypnotics, inhalation anesthetics and a variety of drugs are used that ensure the multicomponence of general anesthesia, thereby increasing the chemical load on the patient's body.
It is known [16,23,36] that the toxic effect of any xenobiotic, including drugs for anesthesia, is realized through a number of common cellular mechanisms:
1. hypoxia;
2. membrane toxicity;
3. oxidative stress;
4. enzymatic toxicity (more often by inhibiting enzymes)
Multiple nature of mechanisms of action, heterogeneity of the cellular elements in target organs, complex space-time interactions of the active drug and receptor determine its bioavailability, pharmacokinetics, pharmacodynamics and toxicity [8, 14, 44]. This determines the difficulties of an integrated assessment of the narcotic effect of anesthetics comparing their efficacy and it has generated a variety of indices and their variants [17,26,34]. For an adequate assessment, generalized description and consideration of the established regularities the bispectral index (BIS) is increasingly used in the clinical practice. It is a monitor of the hypnotic state: anesthesia, which supports BIS at the level of 50-60 (units are a dimensionless value), reduces the probability of undesirable use of memory function under anesthesia. The growth of BIS above 60 is accompanied by increased anxiety, agitation, which persist in the post-operation period. At present, obtaining and analyzing the patient's physiological parameters in real time provides an effective method for continuously assessing the response of administration of the drug to suppress nociception, which allows clinicians to personalize the administration of the drug. The depth of the hypnotic component of anesthesiologic monitors is currently available for most hospitals and is used in the usual way: they record and process simplified electro-encephalographic (EEG) signals and represent the result in real time, which allows anesthetists to correct the introduction of a hypnotic agent to reduce the probability of intraoperative awareness or discomfort of the patient as well as an overdose of the drug [10].
The effect of anesthesia on the respiratory system is carried out primarily by the central mechanism, due to the effect of the drug on the respiratory center. Inhaled anesthetics (IA) lead to a change in rhythm, depth of breathing, the ratio of the phases of inspiration and expiration, a decrease in the sensitivity of the respiratory center to changes in pH, pC02, p02. Virtually all IAs reduce the tone of the respiratory muscles as a result of the central and peripheral effect, thus reducing the respiratory volume [22]. Compensatory increase in the frequency of respiratory movements does not lead to a normalization of the pC02 index in a number of cases. In addition, suppression of the ventilatory reaction to hypercapnia and hypoxemia is noted.
Besides the general responses of the body to the use of IA, there is danger associated with the local effects of the drug. Thus, some IAs have a sharp odor and irritate the upper respiratory tract, causing coughing, salivation, bronchospasm, which is fraught with the development of hypoxic conditions, in addition, the production of surfactant is disturbed [1,5]. A number of IAs inhibits the activity of mucociliary epithelium, thus suppressing mucociliary clearance. This explains their accompanying effects on the respiratory tract [19].
It should also be noted the bronchodilating effect of IA, which is carried out by blocking the effect of histamine, without affecting its production, and also by stimulation of GABA receptors blocking the passage of the impulse into the nerve cell [29]. However, prolonged bronchodilation can lead to an increase in the physiological dead space and, as a result, of reflex hy-pocapnia bronchoconstriction - disturbance of oxygenation of the blood with the development of hypoxemia. Thus, it can be concluded that the effect of IA on the respiratory system, in the absence of adequate respiratory support, is accompanied by the development of hy-poxia, which is also a synergist for anesthetics as to affection of the central nervous system (CNS).
Most biological processes, both at the level of an individual cell and the whole organism, occur with the use of ATP energy [2]. For its effective formation, constant delivery of oxygen to the cell mitochondria is required; therefore hypoxic states are accompanied by energy "hunger" of the cell and the whole organism. The condition of energy deficit of the cell entails a number of negative consequences: disturbance of the processes of active transport, protein biosynthesis, cellular metabolism. In addition, hypoxia causes damage to endothelial cells and uncontrolled production of biologically active substances affecting the hemostasis system, vascular tone, development of systemic inflammation [15].
Currently, chemical safety is not given enough attention in anesthesiology. It should be noted that the pharmacokinetic parameters of drugs are studied mainly in healthy volunteers, and in patients with the existing concomitant pathology, and even in the combined application mode, they can vary significantly. At the same time, chemical hazard under certain circumstances (psychosomatic state of the patient, sex, age, nature of nutrition) can be realized not only as a result of overdose or inadequate combination of drugs, but also due to the changed mechanisms of the body's response to pharmacotherapy. However, these aspects of anesthesiological support for patients with surgical profile are still insufficiently studied.
Conclusions
1. In surgical practice anesthesia refers to complex medical technologies characterized by a systemic approach, stage, a clear hierarchy of methods used, means and a wide variety of anesthetics used.
2. The creative potential of the anesthetist in the framework of traditional views and protocols is evaluated in most cases by his direct involvement in the surgical intervention, leaving without sufficient attention the preparatory and postoperative stages when the specific mechanisms of action of the anesthetic take the
second place, and against the background of surgical trauma, decreased adaptation reserves, the toxic effects of the combinatorial, cumulative and disregulatory plan develop, which significantly affect the time and completeness of the restitution process, probability and severity of complications.
3. Ensuring chemical safety of the patient at all stages of surgery and recovery is an urgent problem, the solution of which dictates the need for a comprehensive clinical and experimental studies aimed at the establishment of regularities, study of mechanisms of toxic effects associated with exposure to anesthetics, the products of their metabolism as well as probable combined action together with the pharmaceuticals used during chemotherapy.
4. Comprehensive research should cover all main units of the functional system from a molecular, cellular to the whole organism, with obligatory consideration of individual personal patient's characteristics for his well-being and quality of psychosomatic subsequent life activity.
To solve this problem, a complex of clinical and experimental studies has been planned and started.
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АДСОРБЦИОННО-РЕОЛОГИЧЕСКИЕ СВОЙСТВА КРОВИ ПРИ РЕВМАТОИДНОМ
АРТРИТЕ
Синяченко О.В.
доктор медицинских наук, профессор, Донецкий национальный медицинский университет, Лиман, Украина (заведующий кафедрой внутренней медицины)
Бреславец А.В. кандидат медицинских наук, Центр клинической и профилактической медицины, Киев, Украина
(научный сотрудник) Ливенцова Е.В. кандидат медицинских наук, Донецкий национальный медицинский университет, Лиман, Украина (ассистент кафедры внутренней медицины)
Чистяков Д.А.
Донецкий национальный медицинский университет, Лиман, Украина (ассистент кафедры внутренней медицины)
ADSORPTIVE AND RHEOLOGICAL PROPERTIES OF BLOOD IN RHEUMATOID ARTHRITIS
Syniachenko O. V.
DM, Professor, Donetsk National Medical University, Lyman, Ukraine
(Head of Department) Breslavets A. V.
PhD, Centre of Clinical and Preventive Medicine, Kyiv, Ukraine
(The research Assistant) Liventsova K. V.
PhD, Donetsk National Medical University, Lyman, Ukraine
(The Assistant of Department) Chystiakov D.A.
Donetsk National Medical University, Lyman, Ukraine (The Assistant of Department)
Аннотация
Ревматоидный артрит протекает с изменениями вязких и релаксационных свойств сыворотки крови, причем второй физико-химический параметр в этой группе больных имеет разную (увеличенную и уменьшенную) направленность. Заболевание суставов отличается более высокими значениями времени релаксации сыворотки крови и превалированием показателя модуля вязкоэластичности при ревматоидном артрите, параметры которых коррелируют между собой, с поверхностной вязкостью и упругостью, зависят от клинических признаков течения болезни, уровней сывороточных сурфактантов и поверхностнор-неактив-ных веществ. Адсорбционно-реологические свойства сыворотки крови влияют на характер агрегации эритроцитов и тромбоцитов цельной крови. Отдельные показатели сывороточной реологии коррелируют между собой, хотя характер этих взаимоотношений разнится, параметры имеют корреляционные связи с индексом агрегации эритроцитов.
