RU2848463C1 - Method of short-term inhalation analgesic therapy - Google Patents

Abstract

FIELD: medicine.

SUBSTANCE: the invention relates to medicine, specifically anaesthesiology, and can be used for inhalation analgesic therapy with a xenon-oxygen gas mixture. To implement the method, a reversible breathing circuit is used, which contains a container with a mixture of xenon and oxygen in a ratio of 60:40% and a volume of no more than one litre, a face mask, a non-reversible breathing valve and a breathing bag with a volume of three to six litres. The method is carried out in stages. In the first stage, the patient takes a slow, unforced breath of the mixture into their lungs, after which the supply of the gas mixture is stopped. Then they move on to the second stage: the patient breathes through a closed "lungs-breathing bag" circuit three times for two minutes within fifteen minutes, but with an interval of at least two minutes between procedures.

EFFECT: pronounced analgesic effect.

6 dwg, 13 tbl

Description

The invention relates to the field of medicine.

The inert gas xenon has analgesic, hypnotic and neuroprotective properties and is used as an inhalation anesthetic during invasive interventions and chronic pain syndrome (Burov N.E., Potapov V.N. Xenon in medicine: essays on the history and use of medical xenon. Moscow: Pulse, 2012. - 640 p.). Xenon can also be used in the field for pain relief and sedation of victims in emergency situations, for the treatment of chronic pain syndrome in cancer patients outside the hospital, as well as for the restoration of the body's functional reserves in individuals subject to high psychoemotional stress (Potievskaya V.I., Shvetsky F.M., Potievsky M.B. Study of the bioelectrical activity of the brain during the procedure of mask inhalation of a xenon-oxygen mixture. Bulletin of Intensive Therapy named after A.I. Saltanov. 2019; (1): 94-99; Shvetsky F.M., Potievskaya V.I., Potievsky M.B. Prospects for using the adaptive properties of xenon in space medicine. "The human factor in air, water and land transport." Proceedings of the 10th scientific and practical conference dedicated to the 25th anniversary of the creation of the All-Russian public organization "Association "Aviation, space, marine, extreme and environmental medicine of Russia." 2017:251-252.).

The problem solved by creating the claimed invention was reduced to further improvement of methods of pain treatment, reduction of the psychoemotional component of pain syndrome, increase of the threshold of sensitivity and endurance when exposed to an external or internal irritant of pain receptors with a xenon-oxygen gas mixture, the use of which is possible in field conditions, confined spaces, independently and/or within the framework of mutual assistance, by medical personnel and/or unqualified victims and rescuers.

The technical result achieved by solving this problem consists in increasing the safety of the procedure of short-term inhalation analgesic therapy with a xenon-oxygen mixture up to and including the achievement of a stable analgesic effect.

In order to achieve the set result, a method of short-term analgesic inhalation of a xenon-oxygen gas mixture is proposed, using a reversible breathing circuit containing at least a container with the said mixture, a face mask, a non-reversible inhalation valve and a breathing bag, including a first stage of smooth supply of the mixture from the container to the patient requiring inhalation, unforced slow inhalation of the mixture with a full chest followed by cessation of the supply of the mixture, and a subsequent second stage of breathing by the patient along a closed circuit "lungs - breathing bag" for no more than two minutes or less until the onset of a subjective sensation of analgesia, wherein, in the absence of a stable effect based on the results of the second stage, the entire procedure is repeated, but no more than three times within fifteen minutes. with an interval of at least two minutes between procedures. The volume of the breathing bag is from three to six liters, the volume of the container with the mixture is no more than one liter, and the mixture consists of 60% xenon and 40% oxygen.

Fig. 1 shows the dynamics of the decrease in the percentage of oxygen in a closed breathing circuit during mask inhalation of a xenon-oxygen mixture of 60/40 percent gases, respectively, without including an adsorber with soda lime in the breathing circuit;

Fig. 2 - dynamics of _CO2 changes (capnography);

Fig. 3 - dynamics of changes in the gas composition of arterial blood and oxygen saturation before and after inhalation of a xenon-oxygen mixture;

Fig. 4 shows the dynamics of changes in reactive anxiety;

Fig. 5 - changes in the differences in EEG power in various wave spectra under the influence of inhalation of a xenon-oxygen mixture (60/40) for 2 minutes, %. N=20;

Fig. 6 - changes in zonal differences in EEG power in the delta-2 range under the influence of inhalation of a xenon-oxygen mixture (60/40) for 2 minutes, %. N=20.

The possibility of achieving the desired result within the framework of the declared method is determined by the following cause-and-effect factors:

- for safety purposes and to prevent barotrauma, the volume of the inhaled mixture at the first stage is limited to one active physiological breath after the gas mixture is supplied and its cessation after the end of the inhalation;

- limiting the inhalation time at the second stage to no more than two minutes, on the one hand, allows for achieving the maximum therapeutic effect, on the other hand, it limits the exposure time to ensure safety and prevent the development of deep sedation while continuing the procedure;

- the second stage of inhalation is carried out through a closed reversible breathing circuit, limited by the volume of the breathing bag from three to six liters, which ensures free breathing and reversal of the air-gas mixture, helps ensure safety during autoanalgesia, since it accumulates carbon dioxide, which stimulates the respiratory center and, in addition, ensures passive refusal to continue the stage lasting more than two minutes - see above;

- The gas mixture composition and exposure time during the short-term inhalation procedure are below the minimum alveolar concentration (MAC), which is responsible for the initial stage of anesthesia and possible manifestations such as profound depression of consciousness, profound muscle relaxation, reflex suppression, possible asphyxia, and aspiration. However, the MAC does not fall below the effective effect on the posterior horn of the spinal cord's lamina propria, subcortical structures, and the cerebral cortex, providing adequate analgesia, reducing skeletal muscle hypertonicity, influencing the release of endogenous peptides, stimulating stress-limiting effects that ensure an overall positive emotional profile during the procedure, and on NMDA receptors in the brain, causing anxiolytic and hypnotic effects. A decrease in calcium ion entry during ischemia reduces the cell's area in the brain. In the myocardium, it stimulates the release of protective myocardial kinases and suppresses the activity of stress hormones in the adrenal glands, creating a stress-tolerant phase as the body's protective response, without transitioning to the exhaustion phase. The effect on the spinal cord roots is achieved 30 seconds after the first inhalation, on the subcortical structures - 60 seconds after the start of inhalation. Effective action on the cerebral cortex is achieved 90 seconds after the start of inhalation, and the required therapeutic effect is achieved after 120 seconds of inhalation under the stated concentration of xenon and oxygen in the mixture.

The following examples confirm the possibility of realizing the stated purpose and achieving the desired result.

Example 1. Assessment of the dynamics of changes in carbon dioxide and oxygen.

In order to evaluate the gas composition of the mixture in the breathing circuit during a short-term two-minute inhalation through a closed reversible circuit, the dynamics of changes in carbon dioxide and oxygen were assessed using the INSOFT-GKM 03 gas analyzer without turning on the soda lime adsorber for up to two minutes and using carbon dioxide sorption for up to four minutes of inhalation with a xenon-oxygen mixture at a concentration of 60/40 percent xenon and oxygen, respectively.

Indications for the experiment are mask inhalation of a xenon-oxygen mixture for four minutes. During the second minute, while inhalation continues, the circuit should be filled with a fresh mixture. However, for up to two minutes inclusive, no critical threshold of carbon dioxide accumulation in the reservoir is observed.

Based on the results of the first study, Fig. 1 shows a graph showing the dynamics of changes in the composition of the gas mixture of the breathing circuit without including a carbon dioxide adsorber in the circuit, from which it follows that a decrease in the oxygen content to 22% with a closed circuit occurs by the end of the 2nd minute.

In the second study, the dynamics of carbon dioxide increase were assessed in two cases: without the inclusion of a soda lime adsorber in the circuit and with _CO2 sorption. According to capnography data (Fig. 2), an increase in carbon dioxide to 4% occurs at the end of the second minute of inhalation in both cases, but with the inclusion of a soda lime adsorber in the breathing circuit, as inhalation continues, the increase in _CO2 reaches a plateau lasting up to 4 minutes. When conducting mask inhalation of a xenon-oxygen mixture with the inclusion of an adsorber, an additional supply of fresh mixture is required in the second minute, which coincides with the data on measuring the dynamics of oxygen concentration in the breathing circuit. When a soda lime adsorber is included in the breathing circuit, the mixture of caustic soda and slaked lime absorbs water and carbon dioxide with the release of heat, resulting in a heated gas mixture in the breathing circuit from the beginning of the second minute of inhalation.

Thus, according to the study of the breathing mixture in a closed circuit, the data confirm the changes in the gas composition of peripheral arterial blood during short-term inhalation of a xenon-oxygen mixture of 60/40%, respectively, for 2 minutes through a reversible closed circuit without turning on the carbon dioxide adsorber.

According to the study of the gas composition of arterial blood, reliable changes were obtained in the form of a significant increase in the partial pressure of oxygen and a moderate decrease in carbon dioxide, while the values of oxygen saturation changed significantly in the direction of their increase - Fig. 3.

Example 2.

The most informative indicator of cardiovascular function is mean arterial pressure (MAP), one of the most strictly homeostatic parameters of systemic hemodynamics. Its normal values are 85-90 mmHg and vary slightly under the influence of adverse environmental factors. An increase in MAP above 90 mmHg is considered a sign of borderline hypertension and indicates a decrease in the reserve capacity of the circulatory system. Low MAP values, which are often detected in humans, indicate a tendency toward physiological hypotension and are transient.

The data obtained during a two-minute inhalation of a 60/40% xenon-oxygen mixture, respectively, in a closed circuit, demonstrate the stimulating effect of the xenon-oxygen gas mixture on the circulatory system, which is manifested by a statistically significant increase in mean arterial pressure in the first series of the study by an average of 7.2% immediately after inhalation.

In subsequent series, the inhalation procedure caused a decrease in mean arterial pressure by an average of 7.5%. In the control group, mean arterial pressure values measured the following morning after the regimen-control training did not change statistically significantly - see Table 1. Thus, during inhalation of a xenon-oxygen mixture for two minutes with a high concentration of xenon in the mixture (60%) in the first series, a slight increase in mean arterial pressure values was noted.

Table 1. Mean arterial pressure (mmHg), dynamics of change

Meaning Experimental group Control group Evening before inhalation Evening after inhalation The next morning Evening after training The next morning Episode 1 quartile 1 75 84 79 73 77 quartile 3 89 88 82 80 82 median 80 84 80 79 82 Episode 2 quartile 1 75 69 83 78 73 quartile 3 83 90 85 85 76 median 76 75 84 85 74 Episode 3 quartile 1 74 72 79 76 76 quartile 3 79 73 83 82 80 median 75 72 82 82 79 Comparison of series Kruskal-Wallis criterion 0.72 0.69 0.25 0.66 0.88

It should be noted that increased blood pressure is one of the most characteristic manifestations of any psychoemotional experience. Under natural, everyday conditions, any changes in blood pressure in healthy individuals caused by emotional factors or physical exertion are always episodic, and blood pressure always returns to normal. In the second and third series of the study, mean arterial pressure statistically significantly decreased during the 2-minute closed-circuit procedure, which is apparently explained by the subjects' gradual familiarization with the hypnotic effects of xenon (see Table 2). Consequently, subsequent inhalations did not produce such a pronounced euphoric reaction, and there was no increase in mean arterial pressure. Instead, the effects of deep relaxation with corresponding changes in systemic hemodynamics began to come to the fore.

Table 2. Mean arterial pressure (mmHg), comparison results between groups

Groups Comparison groups Episode 1 Episode 2 Episode 3 Experimental group Evening Before/Evening After 0.178 0.178 0.178 Evening after/morning 0.225 0.225 0.225 Evening before/morning 0.787 0.787 0.787 Control group Evening/after morning 0.350 0.350 0.350 Experimental/control group Inhalation/training 0.421 0.548 0.421 Morning/morning 0.841 0.008 0.690

Example 3. Method of mask anesthesia with a xenon-oxygen mixture in combination with non-opioid analgesics by short inhalations for two minutes with a high concentration of xenon mixed with oxygen 60/40% in a closed reversible circuit using portable equipment (a 600 ml cylinder with a face mask and a breathing reservoir) of patients following short-term surgical intervention.

After surgery, patients in the 1st group (ketamine/seduxen) experienced a significant decline in cognitive function due to the pronounced psychotic effects associated with these medications. Patients reported feelings of emotional discomfort, including dysphoria, for two hours after surgery (see Table 3). In the 2nd group (propofol/fentanyl), no such effects were observed, but many patients reported weakness and drowsiness, which they experienced for half an hour to an hour and a half after the procedure. In the 3rd group (xenon/nalbuphine), patients consistently felt subjectively better and did not report any cognitive impairment; they were able to move independently immediately after awakening. Postoperative pain was most severe in patients in the propofol/fentanyl group. Patients in this group described severe postoperative pain, scoring 7-8 on the VAS, which increased the need for analgesics (the maximum severity being morphine). In Group 1 (ketamine/seduxen), pain was less severe, as reflected in the visual analog scale (VAS) rating of 4 to 6, corresponding to moderate pain intensity. However, many respondents in this group described pain as various paresthesias localized in the postoperative wound area. In Group 3 (xenon/nalbuphine), pain scored 2-4 on the VAS, corresponding to low-intensity pain.

Table 3. Duration of interventions and recovery of consciousness.

Type of general anesthesia, number of patients Consumption of drugs Duration of operation, min Recovery of consciousness, min Residual sedation, min 1st group (n=20):
ketamine/seduxen Ketamine
2 mg/kg;
Seduxen
0.3 mg/kg 1-2 7-12 60±15 2nd group (n=20):
propofol/fentanyl Propofol
2 mg/kg;
Fentanyl
25 mcg/kg 1-2 5-7 40±7 Group 3 (n=20):
xenon/oxygen/nalbuphine Xenon 2-4 l
Nalbuphine
0.3 mg/kg 1-2 1-3 6±1.5

The data presented in Table 3 show that, despite relatively similar patient body weights (82.5±5.5 kg) and surgical durations, the time to recovery varied between the operated patients. While recovery time for patients in the first group (ketamine/seduxen) was 7-12 minutes, recovery was significantly faster with the use of a xenon/oxygen anesthetic mixture combined with intravenous nalbuphine.

Table 4 presents data on the study of changes in central hemodynamic parameters under the three types of anesthetic protection applied. The analysis of hemodynamic parameters revealed a significant decrease in total peripheral vascular resistance (TPVR) in patients in Group 2 (propofol/fentanyl), an increase in this parameter in those operated on in Group 1 (ketamine/seduxen), and virtually unchanged parameters in patients in Group 2 (xenon/nalbuphine). At the same time, no changes in cardiac index (CI) were recorded in patients in the xenon/nalbuphine group; in the other two groups, a decrease of this parameter by 6.3% from the baseline level was noted during anesthesia. The xenon-oxygen mixture did not lead to significant changes in hemodynamics and myocardial contractility. Heart rate (HR) increased to a greater extent (17.9%) compared to baseline in patients in Groups 1 and 3 than in Group 2, while systolic and diastolic blood pressure did not decrease in Group 2. An increase in these parameters was noted in Group 1, while in Group 3 they remained virtually unchanged (8.8% and 14.8%).

Table 4

Comparative studies revealed significant differences between the three anesthetic methods. A xenon-oxygen mixture with a 2-minute exposure and a 60% xenon mixture, combined with nalbuphine, unlike traditional intravenous anesthesia methods, has virtually no cognitive impairment, has a minor impact on hemodynamics, and provides adequate analgesia for this type of surgical procedure. This makes it a promising alternative to existing anesthetic protection methods used in modern outpatient anesthesiology.

Example 4. Increased testosterone concentration in the blood.

Testosterone is a sex hormone with a pronounced anabolic effect, promoting rapid restoration of functional state during stress.

The magnitude of changes in blood hormone levels depends on the severity and duration of stress. Changes in blood hormone levels can be used to assess the body's adaptation, the intensity of the metabolic processes they regulate, and the development of fatigue. In the first study, after completing a 2-minute inhalation procedure of a 60/40% xenon-oxygen mixture via a closed circuit using portable equipment, a slight decrease in testosterone concentration was noted in the study group by an average of 34.8% (see Table 5). The following morning, testosterone concentrations remained reduced relative to baseline values by an average of 16.2%. In the control group, testosterone concentrations also significantly decreased in the first study series by an average of 4.9% (p ≤ 0.01 according to the Wilcoxon t-test). The difference in the decrease in testosterone concentration in the blood of the study and control groups was not significant. In the second series of the study, no statistically significant changes in testosterone concentrations were observed in the study group after inhalation of a xenon-oxygen gas mixture containing 60% xenon for 2 minutes. However, the following morning, plasma hormone concentrations significantly increased by an average of 78.4%. No statistically significant changes in plasma testosterone concentrations were observed in the control group. In the third series of the study, after inhalation of the gas mixture, the study group experienced a significant decrease in hormone concentrations by an average of 17.2%. Measurements conducted the following morning revealed an increase in testosterone levels by an average of 27.3%. The control group did not experience statistically significant changes in testosterone concentrations.

Table 5. Testosterone concentration (ng/ml). Dynamics of change

Meaning Experimental group Control group Evening before inhalation Evening after inhalation The next morning Evening after training The next morning Episode 1 quartile 1 19.05 12.25 15.75 19.4 18.5 quartile 3 22:45 15.6 19.5 20.7 19.7 median 20.7 14.2 16.5 20.4 19.1 Episode 2 quartile 1 15.9 8.6 21.5 14.8 20.8 quartile 3 22.95 16.85 34.45 21.7 33.7 median 16.8 16.4 26.1 16.5 27.2 Episode 3 quartile 1 13.25 12.85 16.35 17.9 18.7 quartile 3 20.1 17.85 20.25 20.2 19.7 median 14.3 14.5 18.8 19.1 19.3 Comparison of series Kruskal-Wallis criterion 0.4 0.7 0.08 0.63 0.16

Table 6. Testosterone concentration, comparison results between groups

Groups comparison groups Episode 1 Episode 2 Episode 3 Experimental group Evening Before/Evening After 0.018 0.018 0.018 Evening after/morning 0.018 0.018 0.018 Evening before/morning 0.018 0.018 0.018 Control group Evening/after morning 0.043 0.043 0.043 Experimental/control group Inhalation/training 0.074 0.516 0.192 Morning/morning 0.626 1,000 0.871

Across all study series, a 53.5% average decrease in cortisol levels was observed after a 2-minute inhalation of a xenon-oxygen mixture (Table 7). However, a significant increase of 489% was recorded the following morning. In the control group, a 369% average increase in cortisol levels was also recorded the morning after exercise.

Table 7. Cortisol concentration (ng/ml), dynamics of change

Meaning Experimental group Control group Evening before inhalation Evening after inhalation The next morning Evening after training The next morning Episode 1 quartile 1 139.5 87 668 127 659 quartile 3 243.5 124 726.5 205 673 median 178 96 690 183 664 Episode 2 quartile 1 144.5 89 635.5 95 597 quartile 3 198 195.5 789 171 628 median 163 141 750 119 624 Episode 3 quartile 1 186.5 124.5 671.5 110 626 quartile 3 327 320 1175 215 663 median 203 171 918 172 647 Comparison of series Kruskal-Wallis criterion 0.59 0.11 0.39 0.76 0.12

Table 8. Cortisol concentration, results of comparison between groups

Groups Comparison groups Episode 1 Episode 2 Episode 3 Experimental group Evening Before/Evening After 0.043 0.043 0.018 Evening after/morning 0.018 0.018 0.018 Evening before/morning 0.018 0.018 0.018 Control group Evening/after morning 0.043 0.043 0.043 Experimental/control group Inhalation/training 0.074 0.745 0.626 Morning/morning 0.516 0.194 0.330

The data obtained suggest that short-term, 2-minute inhalations of a 60/40% xenon-oxygen mixture have little effect on plasma cortisol levels, but contribute to its reduction and mitigate the adverse effects of the stress response during the short-term inhalation. The sharp increase in blood hormone levels the following day slightly exceeds the upper limit of normal and is explained by the diurnal cycle of cortisol secretion.

Example 5. Assessment of the level of reactive and personal anxiety.

Typically, reactive or situational anxiety is understood as a condition characterized by subjectively experienced emotions: tension, worry, concern, and nervousness. This condition arises as an emotional reaction to a stressful situation and can vary in intensity and dynamism over time. A certain level of anxiety is a natural and essential characteristic of an active, dynamic personality, which ensures an adequate degree of mobilization of a person's physical and mental reserves in extreme situations. However, excessive anxiety triggers pathological adaptation mechanisms, leading to a significant reduction in functional resilience and negatively impacting performance. The data obtained indicate that a series of short, 2-minute inhalations of a xenon-oxygen mixture containing 60% xenon reduces excessive levels of reactive anxiety, helping to maintain it at a certain physiological level.

As Figure 4 shows, at the initial stage, the level of reactive anxiety in both groups was approximately equal, but as the study progressed, the anxiety level of the volunteers in the study group gradually decreased, while it increased in the control group. By the time of peak physical activity, the level of state anxiety in the volunteers in the study group was, on average, 11% lower than baseline, while in the control group, it was, on average, 6.5% higher than baseline values.

Example 6. The results of recording the biopotentials of the cerebral cortex were carried out directly during a two-minute mask inhalation of a xenon-oxygen mixture of 60% xenon and 40% oxygen using portable equipment (a 600 ml cylinder in a closed reversible circuit).

Parameters of various characteristics of the biopotentials of the cerebral cortex (in particular, EEG power indicators) are reliable markers of the state during physical fatigue and psycho-emotional stress.

Already in the initial stages of the procedure, the EEG pattern underwent changes, manifested by an increase in slow-wave rhythms. Then, after one minute, an increase in the relative power of slow-wave activity was noted, with the formation of theta and delta rhythm loci. Their most typical localization was observed in the frontal lobes, predominantly on the left, although the pattern of zonal rhythm changes was often absent even in the same subject during repeated procedures. As the procedure continued, at the second minute, a decrease in the spectral activity of the alpha rhythm was noted, with it remaining most pronounced in the occipital lobes.

During the procedure, there was an increase in the EEG power of the delta-2 range. During direct inhalation of xenon, the total power of the analyzed frequencies exceeded the background values by an average of 49%. Xenon inhalation led to a predominant increase in the EEG power of the delta-2 range in the O2 (by an average of 41%), F4 (by an average of 24.8%) and F3 (by an average of 30%) leads. The analysis showed that when volunteers inhaled a xenon-oxygen mixture for two minutes, a reliable decrease in the relative EEG power of the alpha range was observed by an average of 13% - Fig. 5, the data are presented as a median where *changes are reliable compared to baseline values, p <0.05; **changes are reliable compared to baseline values, p <0.01.

Despite the decrease in alpha-range power, a statistically significant redistribution was observed in the cerebral cortex. Thus, the alpha rhythm became more pronounced in the occipital regions of the cortex (the O1-F3 difference increased by an average of 13% after the experiment). Moreover, during direct xenon inhalation for two minutes, the alpha rhythm spread to the frontal lobes (the O1-F3 difference decreased by 13%, and the O2-F4 difference by 32%) - see Fig. 6, the data are presented as a median, where *changes are significant compared to baseline values, p < 0.05

Observations made during the study revealed specific features of brain bioelectric activity during a 2-minute inhalation of a xenon-oxygen mixture. The most important of these was the complete preservation of awareness and volitional control during the procedure. Furthermore, it was noted that the inhalations also performed a number of restorative functions characteristic of physiological sleep.

Example 7. Evaluation of optimization of medical care for patients with burn injuries by reducing the risk of possible complications of general anesthesia.

The main objective was to evaluate the adequacy of analgesia with short-term xenon monoanesthesia, 2-minute inhalations of a 60/40% xenon-oxygen mixture, respectively, using portable equipment through a face mask during dressings and surgical treatment of wounds, reducing and eliminating from the arsenal of anesthetic care the use of narcotic, psychotropic and sedative drugs in the elderly, weakened patients, patients with severe concomitant pathology, patients requiring frequent dressings, patients with local burns and a labile nervous system.

Analyzing the dynamics of blood pressure, heart rate, and total vascular resistance recorded by us at various stages of dressing, when dressing burn wounds, we noted a stable level of hemodynamic parameters in patients, the absence of vital function impairment: hypotension, bradycardia, apnea, and impaired consciousness.

After the first minute of inhalation, the level of systolic blood pressure (BPs) in patients from the main group was 140±3.8 mmHg, diastolic blood pressure (BPd) - 80.3±4.5 mmHg, mean arterial pressure (BPsm) - 120.1±4.2 mmHg. At the most traumatic stages of dressing, BPs corresponded to the values of 138.7±2.7 mmHg, BPd - 85.4±1.9 mmHg, and BPsm - 121.0±2.3 mmHg. By the end of the procedure, the level of blood pressure in patients of the main group was, respectively: BPs - 145.2±1.8 mmHg, BPd - 91.9±2.3 mmHg. Art., APm - 127.5±2.1 mmHg. Heart rate (HR) after the start of mask inhalation, according to the data obtained, averaged - 84.8±3.7 beats per min, at the traumatic stages of dressing - 83.8±2.4 beats per min, and by the end of the intervention - 86.2±1.11 beats per min. Total peripheral vascular resistance (TPVR) in patients of the main group after induction had an average value of 1252.1±92.4 dyn.s.cm ^-5 . As we approached the traumatic moment of dressing, the TPVR indicator decreased to the level of 1118.4±56.4 dyn.s.cm ^-5 . By the end of the manipulation, the observed decrease in TPVR reached values of 1048.5±78.6 dyn.s.cm ^-5 . The level of BPs in patients of the control group averaged 150.4±3.5 mmHg, BPd - 87.3±2.5 mmHg, BPav - 129.3±3.1 mmHg. HR corresponded to the level of 95.6±4.2 beats per min. Total peripheral vascular resistance had an average value of 1218.6±78.4 dyn.s.cm ^-5 . Analysis of changes in peripheral hemodynamic parameters in patients of this group indicates that at the most traumatic stages of dressings, the level of BPs increased on average to 154.3±2.7 mmHg, BPd to 91.4±2.1 mmHg, BPav to 133.1±2.4 mmHg. art., the heart rate remained virtually unchanged, averaging 97.2±2.3 beats per minute, and the total peripheral vascular resistance increased to 1264.4±84.2 dyn.s.cm ^-5 . By the time the dressing was completed, a moderate increase in s BP to 162.4±1.8 mm Hg, d BP to 92.5±2.7 mm Hg, avg BP to 139.1±2.3 mm Hg, HR to 97.2±2.3 beats per minute and a slight decrease in tPVR to 1252.1±92.4 dyn.s.cm ^-5 were noted. The trends in hemodynamic changes (sBP, BPd, BPm, and HR) with the two anesthetic protection techniques were characterized by the same direction, but patients in the control group demonstrated higher values for all recorded parameters, and this level was maintained throughout the surgical period. However, when analyzing the TPR parameters, a moderate increase was noted in patients in the control group and a moderate decrease in patients in the main group (xenon/silorod) - see Table 9. Thus, the data obtained during the study on changes in the characteristics of central and peripheral hemodynamic parameters indicate greater stability of BPs, BPd, BPm, HR, and TPR in patients in the main group during short-term xenon-oxygen monoanalgesia during traumatic dressings, which generally proves the adequacy and effectiveness of the proposed method of protection from pain and surgical distress.

Table 9

Stage 1 - sequestrectomy;

Stage 2 - treatment of the wound with an antiseptic;

Stage 3 – dressing the burn surface.

Example 8. Study of the possibility of using short-term 2-minute mask inhalation of a xenon-oxygen mixture for procedural sedation during diagnostic esophagogastroduodenoscopy.

Satisfaction with anesthesia was assessed using a questionnaire survey (Table 10).

Table 10

Question Yes No Satisfaction with anesthesia 16 (88.2%) 2 (12.2%) There is pain 4 (13.3%) 14 (77.7%) Foreign body sensation during the procedure 2 (12.2%) 16 (88.2%) Salivation during the procedure 17 (94.4%) 1 (5.6%) Nausea 4 (13.3%) 14 (77.7%) Dizziness 2 (12.2%) 16 (88.8%) Feeling of presence during the procedure 16 (88.8%) 2 (12.2%)

During the study, routine hemodynamic parameters were monitored - heart rate, systolic and diastolic blood pressure, and hemoglobin saturation (Sat O ₂ ).

The time to regain consciousness after the procedure was nearly identical for the volunteers, at 6±1.5 minutes. During the procedure, no loss of verbal communication, no loss of consciousness, and no respiratory distress were observed. Post-procedure questionnaire data showed that, despite the relatively similar duration of the endoscopic procedure, all respondents experienced a sense of presence in the operating room but clearly noted no foreign body sensation during the procedure. No vomiting, nausea, or dizziness were reported by the volunteers after the procedure. Unpleasant sensations included increased salivation and difficulty in saliva drainage. All subjects rated the anesthesia as satisfactory (though some complained, they considered the anesthesia administered to be entirely acceptable).

During EGDS with inhalation of xenon-oxygen mixture, no significant changes in blood pressure and heart rate were observed (Table 11), which further indicates the adequacy of the sedation.

Table 11(M±m, n=18).

Indicators Before the procedure After the procedure P HR/min 74.9±8.1 85.5±7.0 >0.05 BP mmHg 131.5±5.6 120±15.0 >0.05 BP mmHg 82.4±8.2 70.2±8.0 >0.05

Table 12 presents the acid-base balance of the venous blood of the subjects at the beginning of the procedure and at three subsequent blood draws during the diagnostic examination. Based on the data presented in the table, it can be concluded that the feeling of shortness of breath in the volunteers during the procedure was rather a subjective sensation when breathing through a face mask and is not associated with respiratory or metabolic disturbances during inhalation anesthesia. The increase in partial oxygen pressure and blood saturation is due to the inhalation of a hyperoxic mixture (100% oxygen during denitrogenation, 40% oxygen during xenon-oxygen inhalation).

Table 12 (M±m, n=18)

K-BG indicators Before inhalation 1 blood draw 2 blood sampling 3 blood sampling pH(v) 7.39 ±0.36 7.39 ±0.2 7.40±0.03 7.46±0.23 PvCO ₂
(mmHg) 34.2±4.35 35.1±2.11 38.4±6.2 36.4±3.41 PvO ₂
(mmHg) 48.3±6.12 50.8±5.32 62.5± 6.08* 97.3±3.24* BE
mmol/L 3.2±1.01 3.7±0.08 1.9±0.32 1.4±0.06 HCO3
mmol/L 26.6±3.34 29.2±4.08 27.6±3.12 26.8±5.08 Sat O ₂ 96 ±1.0 97±1.0 97±2.0 98±2.0

Note: *p < 0.05

According to the analysis of the variability of cardiac intervals before the EGDS procedure, an increase in sympathetic tone was noted, combined with virtually normal heart rate variability indices, which is typical for healthy individuals experiencing psychoemotional stress (Table 13). After the procedure, an increase in HRV and an increase in the total spectrum power (TP), reflecting the activity of all autonomic influences on heart rate, were noted. An increase in this index indicates an increase in the functional reserves of the cardiovascular system. Mask anesthesia with a xenon-oxygen mixture caused an increase in all frequency indices of the cardiac intervalogram, but the greatest increase was observed in the high-frequency spectrum (HF), characterizing the activity of the parasympathetic part of the autonomic nervous system. The balance of sympathetic and parasympathetic activity is reflected by the index of the ratio of low spectral frequencies (sympathetic activity) to high spectral frequencies (parasympathetic activity). A state of stress is characterized by an increase in the LF/HF index above 2.0. After EGDS with inhalation of xenon-oxygen mixture, a reliable decrease in LF/HF was noted, which indicates adequate anesthesia and the anti-stress effect of this method.

Table 13

Indicators Before the procedure After the procedure Average values for healthy individuals SDNN, ms 64.3±8.8 75.9±6.1* 59.8±5.3 RMSSD, ms 56.6±3.7 70.6±5.2* 42.4±6.1 pNN50% 21.0±2.7 28.3±2.8* 21.1±5.1 TP, ms ² 3005.6±151.1 5018.5±423.6* 3466±1018 VLF, ms ² 900.4±222.4 1463±241.3* 1488±154 LF, ms ² 1875.0±162.4 2183.4±255.6* 1170±416 HF ms ² , 685.2±243.13 1682.0±168.4* 975±203 LF/HF 2.71±0.62 1.29±0.46* 1.5 - 2.0

Note: *p < 0.05

Claims (1)

A method for inhalation analgesic therapy with a xenon-oxygen gas mixture using a reversible breathing circuit containing at least a container with said mixture, a face mask, a non-reversible breathing valve and a breathing bag, including a first stage of smoothly feeding the mixture from the container to a patient requiring inhalation - unforced slow inhalation of the mixture with a full chest followed by cessation of the mixture supply and a subsequent second stage of breathing by the patient along a closed circuit "lungs - breathing bag" three times for two minutes over fifteen minutes, but with an interval of at least two minutes between procedures, wherein the volume of the breathing bag is from three to six liters, the volume of the container with the mixture is no more than one liter, and the mixture consists of 60% xenon and 40% oxygen.