RU2428191C1 - Method of local dosed ozone therapy following gall bladder and/or bile passages surgery - Google Patents

Abstract

FIELD: medicine. ^ SUBSTANCE: invention refers to medicine, particularly to surgery, and can be used for treating and preventing postoperative suppurative complications following gall bladder and/or bile passages surgeries. The method involves insertion of two PVC drainage tubes - inlet and outlet - connected by means a subhepatic space at the completion stage of the surgery in the subhepatic space through a counteropening. From the second postoperative day to the day of removal of the drainage tubes, an ozone-oxygen mixture 80-120 ml with the ozone concentration 10-20 mg/l is introduced daily in the inlet tube at speed 2 ml/sec by means of a disposable Janet's syringe 150 ml. While introducing the first portion 60-80 ml of the ozone-oxygen mixture, an outlet tube clearance is clamped, and the remained portion 20-40 ml is introduced with the outlet tube opened 2-3 minutes later. ^ EFFECT: use of the invention allows reducing number of suppurative septic complications following gall bladder and/or bile passages surgeries due to increasing the ozonisation multiplicity that provides higher efficacy of the postoperative therapy and reduces the general intoxication events. ^ 8 tbl, 1 ex

Description

The invention relates to medicine, in particular to surgery, and can be used for the treatment and prevention of purulent complications and for the systemic correction of homeostasis in the postoperative period during operations on the gallbladder and / or biliary tract.

The known method / Patent of the Russian Federation No. 2192866, class. А61К 33/00, А61М 5/00, А61Р 17/02, BIPM No. 32, 11/20/2002, / treatment of ischemic and purulent-necrotic lesions of the lower extremities, carried out by intraosseous injection of 100-150 ml of ozone-oxygen mixture for 20-30 min at an ozone concentration of 2500-5000 μg / l with a preliminary application of a tourniquet on the limb. However, the use of such a concentration of gaseous ozone may be insufficient for the effective rehabilitation of purulent foci of the lower extremities.

The known method / Patent RF №2324467, class. А61Н 33/14, BIPM No. 14, 05/20/2008 / treatment of body parts with ozone, characterized in that a sterile gas-permeable ozone-resistant material is preliminarily placed on the body part to be treated, covering the area to be treated completely with a margin, a plate is placed on it made of an elastic material resistant to ozone, an exhaust device is installed directly above the plate, and ozone is fed under the plate during the set duration of the procedure and at the same time, the incoming from under ozone plates into an exhaust device with its subsequent decomposition in a destructor. In this case, after the end of the procedure (treatment of the body site with ozone), oxygen is supplied under the plate until it completely replaces the ozone not adsorbed on the gas-permeable material and the treated body area is freed from the exhaust device and the plate. However, this method is intended only for the treatment of superficial wounds and does not have clear indications due to the lack of a given dosage and treatment regimen with gaseous ozone.

Closest to the proposed is the method / Patent of the Russian Federation No. 2194513, class. А61К 33/00, А61К 33/14, A61P 31/00, BIPM No. 35, December 20, 2002 / decontamination of the gastrointestinal tract with ozone in patients with pancreatic necrosis, carried out by introducing in the postoperative period an ozonized physiological solution into the lumen of the small intestine through a nasointestinal probe for 7 days at an ozone concentration of 4-7 mg / l, a volume of 200 ml and simultaneous rectal insufflation of the ozone-oxygen mixture from 1 day of the postoperative period at a concentration of 30 mg / l, a volume of 300 ml and an exposure of at least 15 minutes, while 7 insufflations with a break of 3-4 days. However, this method does not allow the removal of excess volume of the gas mixture during insufflation, which, with accelerated introduction and prolonged exposure to ozone, can create excessive gas pressure inside the intestine and contribute to the multiple enhancement of the resorptive and local toxic effects of high concentrations of ozone-oxygen mixture. At the same time, sessions of rectal insufflations are carried out not daily, but at long time intervals, which reduces the antimicrobial effect against the background of a high risk of ozone intoxication.

The objective of the proposed method is to reduce the number of purulent-septic complications after operations on the gallbladder and / or biliary tract, reducing the phenomena of general intoxication.

The problem is solved due to the fact that at the final stage of the operation, two polyvinyl vinyl drainage tubes are installed in the subhepatic space through a contraperture, leading and discharging, communicating with each other through the subhepatic space, from the second day of the postoperative period until 80 drainage tubes are removed -120 ml of an ozone-oxygen mixture with an ozone concentration of 10-20 mg / l at a rate of 2 ml / sec using a disposable 150 ml Janet syringe, while First 60-80 ml of ozone-oxygen mixture lumen outlet tube clamp overlap, and the remaining 20-40 ml administered under open outlet tube after the 2-3 minute pause.

The method is carried out as follows: at the final stage of the operation on the gallbladder and / or biliary tract (e.g. cholecystectomy), two polyvinyl vinyl drainage tubes are installed in the subhepatic space through the counter-opening, leading and discharging, communicating with each other through the subhepatic space. Next, from the second day of the postoperative period, 80-120 ml of an ozone-oxygen mixture with an ozone concentration of 10-20 mg / l is injected into the subhepatic space through a lead tube using a 150 ml disposable syringe, which is attached to the proximal end of the lead tube using a plastic adapter. Prior to this, the ozone-oxygen mixture is collected in a sterile sealed container with a volume of 1-2 liters, pre-connecting it to the “ozone” fitting of the ozone producing unit and setting a certain concentration, flow rate, and ozone synthesis and supply time. Then, the Janet syringe is filled with gaseous ozone, connecting it to the edge of the sealed container, after which the syringe is connected to the lead tube using a plastic adapter, and the outlet tube is closed with a clamp to seal the subhepatic space. Ozone gas is introduced slowly at a rate of 2 ml / sec to maximize gas distribution and eliminate pain. After the introduction of 60-80 ml of the gas mixture, the Janet syringe is left on the lead tube, wait about 2-3 minutes, and the remaining volume of gas is injected with the open lead tube, providing free passage and exit of ozone into the environment. Sessions of ozone therapy are carried out daily from 2 days of the postoperative period during the entire drainage period until the drainage tubes are removed, which is carried out depending on the severity of the postoperative period, the presence of purulent complications - for 4-10 days.

The mechanism of action of gaseous ozone at a given concentration is based on a pronounced local antibacterial effect, as well as on the resorptive effect on free radical processes in organs and tissues due to the absorption and entry of ozone from the local exposure into the bloodstream at lower concentrations, which ensures the following main points: 1) restoration of oxygen transport function of blood; 2) a pronounced effect on the metabolic processes of the body through ozonolysis of organic substrates; 3) moderate initiation of free radical lipid peroxidation (LPO) reactions with the simultaneous prevalence of antioxidant defense mechanisms; 4) activation of enzyme systems and restoration of the energy potential of cells; 5) pronounced hepatoprotective effect; 6) inactivation of enzymes and final toxic metabolic products; 7) a decrease in the level of medium-weight molecules and the activity of non-specific inflammatory mediators.

The use of ozone in the above concentration and volume is not accidental. The optimal gas volume was selected based on the volume of the subhepatic space, taking into account the anatomical formations of this area, as well as the ability of the gas mixture to be absorbed from the abdominal cavity into the blood. Optimal values of ozone concentration were obtained on the basis of clinical and laboratory research methods.

The optimal concentration of ozone in the mixture was clinically selected based on a study of 120 patients of both sexes (12 men and 108 women) aged 35 to 80 years, long-term suffering from gallstone disease, who underwent routine and urgent surgery for acute cholecystitis (cholecystectomy from “mini -Access ”with drainage of the subhepatic space with two polyvinyl chloride drainages). All patients were hospitalized in the acute stage of the disease; upon admission, they were diagnosed on the basis of complaints, medical history, physical data, laboratory tests, and ultrasound findings of the hepatopancreoduodenal zone. In the study of macro- and micropreparations of the gallbladder in patients, a phlegmonous or gangrenous-altered gallbladder was detected. Depending on the histological forms of destructive cholecystitis (gangrenous or phlegmonous), the total number of patients was distributed equally in two histological groups of the studied and comparative patients (60 patients in each histological group). Within the histological group, 15 comparative patients from the first day after surgery received daily traditional treatment in the form of infusion, anti-inflammatory, antibacterial therapy, antispasmodics, analgesics, physiotherapy and diet therapy, and 45 studied patients in the complex traditional treatment from the second day of the postoperative period daily through drainage 80-120 ml of an ozone-oxygen mixture with different concentrations of ozone were injected (15 patients each received ozone at a concentration of 0-10 mg / l, respectively 10-20 mg / l, 20-30 mg / l). For patients with phlegmonous forms of destructive cholecystitis, the drains were removed on the 4-5th day of the postoperative period, and for patients with gangrenous forms on the 7-8th day, thereby completing the cycle of daily ozone therapy sessions. Between all 8 subgroups of both histological groups (comparative patients and the studied patients who received various concentrations of ozone), the patients were distributed evenly by gender, age, severity of the underlying disease, and the presence and severity of concomitant pathologies. Drainage of the common bile duct was not performed in any patient due to the absence of choledocholithiasis in all patients of the studied and comparative subgroups. The main objective of the task of the proposed method is to find the maximum permissible safe concentration of ozone for introduction into the subhepatic space to combat possible infection. The assessment of the adequacy and physiology of the dose of ozone administered in each subgroup was carried out in dynamics based on clinical data and data from laboratory research methods. Statistical processing of the results was carried out according to conventional methods of variation statistics using paired student criterion at a significance level of P <0.05 using the Statistica 5.0 application package for Windows XP. Clinically, in the studied patients of both histological groups who received ozone at a concentration of 0-10 mg / l, the average postoperative bed day was 12 ± 2 days, and the average total bed day was 14 ± 2 days, complete normalization of body temperature occurred at 11 ± 1 day of the postoperative period, of these patients, 7 patients in the postoperative period had complications in the form of suppuration of the postoperative wound, in comparative patients of both histological groups, the average postoperative hospital bed was 13 ± 2 days, and the average total hospital bed was 15 ± 2 days Full normalization of body temperature occurred at 11 ± 2 days after surgery, these patients, 8 people had the same complication. In patients receiving ozone therapy at concentrations of 10-20 mg / l and 20-30 mg / l, the average postoperative hospital bed was 8 ± 1 and 10 ± 1 days, respectively, and the average total hospital bed was 10 ± 1 and 12 ± 1 days, the full normalization of body temperature occurred on 5 ± 1 and 8 ± 1 days of the postoperative period, respectively, and there were no complications of the course of the postoperative period. In the studied patients of both histological groups who received ozone at a concentration of 10-20 mg / l in the postoperative period, the earliest relief of pain was recorded, which occurred on 4 ± 1 day. When using ozone at concentrations of 0-10 and 20-30 mg / l, it occurred on 9 ± 2 and 6 ± 1 days, respectively, and in the comparison subgroups - on 10 ± 1 days. None of the studied patients had any complications from ozone therapy. Thus, the greatest clinical efficacy was noted when using an ozone-oxygen mixture at a concentration of 10-20 mg / l due to the shortening and smoother course of the postoperative period, the earliest normalization of body temperature, the absence of purulent-inflammatory complications in the postoperative period.

Also, blood parameters were studied in dynamics for the studied and comparative patients of both histological groups in order to assess the severity of toxinemia, the phenomena of reactive hepatitis, the effectiveness of antioxidant mechanisms, and the effect of local dose-dependent ozone therapy on these processes. Moreover, in patients with phlegmonous forms of acute cholecystitis, blood was taken on the 1st, 3rd and 5th day of the postoperative period, and in patients with gangrenous forms on the 1st, 3rd, 5th and 7th day. Venous blood sampling in the studied patients of both histological groups was carried out 5-6 hours after the next session of local ozone therapy. Analysis of the severity of endogenous intoxication, the functional state of the liver and antioxidant protection was carried out on the basis of indicators of pigment (total, indirect bilirubin) and protein (total protein, urea, creatinine) metabolism, blood transaminases (alanine aminotransferase (ALT), aspartate aminotransferase (ACT), degree the severity of intoxication syndrome (leukocytes, leukocyte intoxication index according to Kalf-Kalyf (LII), molecules of medium molecular weight (MSM)), the level of lipid peroxidation (malondialdehyde (MDA), diene stems conjugates (DC)) and antioxidant protection (superoksiddesmutaza (SOD), catalase (CAT)). To determine normal laboratory parameters, venous blood was collected to study relevant data in 30 healthy donors of both sexes (4 men and 26 women) aged 35-55 years. The average laboratory blood parameters obtained using various concentrations of ozone and traditional therapy over time, as well as data obtained from healthy donors, are presented in tables 1-8. Upon admission in the studied and comparative patients of both histological groups, a pigment exchange disorder by hyperbilirubinemia was noted mainly due to indirect bilirubin, which is more pronounced in patients with gangrenous forms of acute cholecystitis. The indicators of protein metabolism were also more altered in patients with gangrenous forms of acute cholecystitis due to a decrease in the amount of blood protein, an increase in the content of blood urea and creatinine, which characterize the growth of catabolism. Assessment of the degree of activity of the basic enzymes showed hyperfermentemia for both enzymes (ALT and ACT), which in most patients exceeded normal values by more than 1.5 times, which was more pronounced in gangrenous forms and characterized the initial necrobiotic processes in the liver tissue. For phlegmonous forms, the increase was less significant, mainly due to ALT, which meant the presence of a more moderate liver lesion, in violation of protein metabolism, slight hypoproteinemia prevailed and more azotemia due to urea against a background of normal creatinine levels. The severity of the inflammatory process was characterized by moderate leukocytosis in both histological groups, endogenous intoxication syndrome, accompanied by an increase in LII and MSM, an increase in lipid peroxidation processes and the accumulation of its final products in the form of MDA and DC, inhibition of antioxidant protection, in particular due to a decrease in the activity of SOD and CAT . In the histological group of gangrenous forms of acute cholecystitis in comparative patients and in the studied patients receiving ozone at a concentration of 0-10 mg / l, a similar dynamics of changes in laboratory blood parameters in the postoperative period was noted. So, there was a slight increase in the content of leukocytes compared with the preoperative level in the first day of the postoperative period. The bilirubin level gradually decreased from the first day of the postoperative period to near normal values by 7 days mainly due to the indirect fraction, the ACT values on the 1st day of the postoperative period exceeded the preoperative level by about 1.5 times, and the ALT values by more than 2 times, after which their decrease followed, not reaching the normal level by 7 days, which indicated moderate relief of reactive hepatitis by means of detoxification therapy. Normalization of the level of total protein and urea occurred on the 7th day of the postoperative period, and creatinine - on the 5-7th day. Leukocytosis lasted up to 7 days, but LII, MSM and DC remained elevated and later, MDA decreased to normal by 7 days. Antioxidant activity through SOD and CAT was restored only by 7 days of the postoperative period. In patients with gangrenous forms of acute cholecystitis receiving ozone at a concentration of 20-30 mg / l, indirect bilirubin exceeded the norm throughout the study and decreased very slowly, the ACT and ACT values on the 3rd day exceeded the preoperative level by more than 2.5 times, and by the end of the study, they were overestimated by more than 2 times compared with normal numbers, which indicates a pronounced systemic hepatotoxic effect of blood ozonides, which appeared 1-2 days after the start of ozone therapy, which exacerbates the effects of reactive hepatitis, which ineffective detoxification therapy. Protein metabolism was disrupted mainly due to hypoproteinemia, which increased up to 3 days of the postoperative period, maintaining a relatively high blood urea content from 1 to 7 days with a peak concentration for 3-5 days. Creatinine was relatively high on the 3rd day of the postoperative period, followed by a sharp decline to near normal figures at the end of the study. The use of this dosage of ozone increased the level of toxinemia in comparison with lower concentrations of ozone in the administered volume and induced an inflammatory process throughout the postoperative period, keeping high LII, MDA, MSM and DC values after the first day of local ozone therapy, suppressing the activity of antioxidant enzymes SOD and CAT In patients with gangrenous forms of destructive cholecystitis who received ozone at a concentration of 10-20 mg / l, the indicators of bilirubin, ALT and ACT returned to normal after 3-5 days of the postoperative period, an earlier normalization of total protein, urea, creatinine relative to previously used concentrations was noted ozone. The postoperative parameters of endogenous intoxication were minimal for this pathology, a clear relationship was observed between the start of ozone therapy and an improvement in the blood picture with respect to LII, MDA, MSM and DC, which was supplemented by enhanced work of antioxidant enzymes. When analyzing laboratory data in patients with phlegmonous forms of destructive cholecystitis, a similar picture of the blood dynamics was noted. In comparative patients and patients receiving ozone at a concentration of 0-10 mg / l, in the postoperative period, bilirubin levels gradually decreased to normal by 5 days, the ALT and ACT values for 1 day were more than 1.5 times higher than preoperative values and more than 2 times exceeded the norm with a subsequent decrease, not reaching the norm on the 5th day in most patients. Operational stress had little effect on the amount of total protein, the urea and creatinine levels, which reached normal levels by 3 days of the postoperative period, to a greater extent shifting the level of leukocytes, which remained slightly elevated up to 5 days, the values of LII and DC slightly exceeding the norm on day 5, as well as the value of MDA, which fell to normal on day 5, and MSM, overstated by the end of the study. The concentration of SOD and CAT was restored quite quickly, although the values of the second were still underestimated on the 5th day after the operation. For patients who received an ozone-oxygen mixture at a concentration of 20-30 mg / l after surgery, a relatively slow decrease in bilirubin content, slightly below the norm by 5 days, an additional activation of blood transaminases from the moment ozone therapy was started, an increase in hypoproteinemia, urea and creatinine concentrations was characteristic up to 3 days, a longer decrease in the level of MDA, MSM, DC, blood leukocytes in combination with a later increase in antioxidant protection. When using ozone at a concentration of 10-20 mg / l within the given histological group, the best results were recorded. So, total and indirect bilirubin, creatinine and urea decreased faster, despite a higher initial level, ALT and ACT were normalized by 5 days of the postoperative period, total protein increased faster than in cases using other dosages of ozone, leukocytosis was stopped after 3 days, MDA, MSM and DC normalized on day 5, SOD and CAT were restored on day 3, and by day 5 their activity was significantly higher than normal. In general, for most laboratory blood parameters with phlegmonous forms, the dynamics of changes was significantly better than with gangrenous forms.

Thus, laboratory data showed that the fastest positive effect on most blood parameters was observed during local ozone therapy with an ozone concentration in the ozone-oxygen mixture equal to 10-20 mg / l, which most favorably affected the dynamics of the blood picture in patients with phlegmonous forms of destructive cholecystitis, when using lower concentrations, the results did not differ much from the figures in comparative patients, but at a concentration of 20-30 mg / l, the induced oxidative stress shal reserve the possibility of antioxidant mechanisms, stratifying on postoperative disorders of blood indicators.

Table 1 Averaged laboratory indicators of endogenous intoxication and antioxidant protection in comparative patients with a gangrenous form of acute cholecystitis in dynamics Indicators Registration Dates Before surgery 1 day post 3 days post 5 days p / o 7 day post Norm White blood cells (× 10 ⁹ / L) 9.14 ± 1.83 9.65 ± 1.85 9.03 ± 1.87 8.56 ± 1.69 7.78 ± 1.72 5.83 ± 1.34 Total bilirubin (μmol / L) 36.78 ± 10.15 34.23 ± 8.79 29.15 ± 9.02 25.81 ± 8.23 19.97 ± 6.98 13.78 ± 5.86 Indirect bilirubin (μmol / L) 21.34 ± 5.66 19.34 ± 5.25 16.12 ± 5.42 13.44 ± 5.03 8.96 ± 3.94 7.45 ± 2.61 LII (unit) 3.62 ± 0.93 4.02 ± 1.08 3.22 ± 0.77 2.18 ± 0.54 1.96 ± 0.46 0.73 ± 0.32 ACT (mmol / h * l) 0.56 ± 0.15 0.88 ± 0.21 0.81 ± 0.19 0.75 ± 0.18 0.63 ± 0.16 0.28 ± 0.07 Alt (mmol / h * l) 0.74 ± 0.14 1.66 ± 0.28 1.39 ± 0.26 0.94 ± 0.18 0.72 ± 0.12 0.46 ± 0.09 Total protein (g / l) 53.21 ± 8.56 49.87 ± 7.35 54.39 ± 8.77 56.73 ± 8.8 57.24 ± 8.82 71.12 ± 12.84 Urea (mmol / L) 8.57 ± 2.05 8.99 ± 2.13 8.32 ± 1.96 7.46 ± 1.77 6.71 ± 1.64 5.32 ± 1.53 Blood Creatinine (mmol / L) 0.116 ± 0.029 0.119 ± 0.031 0.115 ± 0.026 0.108 ± 0.024 0.097 ± 0.021 0,083 ± 0,024 MDA (μmol / L) 51.56 ± 12.13 57.18 ± 13.55 49.31 ± 12.09 48.79 ± 11.77 44.62 ± 11.16 32.89 ± 8.43 MSM (c.u.) 0.257 ± 0.052 0.263 ± 0.054 0.252 ± 0.05 0.243 ± 0.046 0.231 ± 0.033 0.221 ± 0.03 DC (c.u. / ml) 33.47 ± 5.89 36.5 ± 6.22 32.96 ± 5.91 30.11 ± 5.65 27.24 ± 5.28 17.45 ± 3.23 SOD E / mg 62.04 ± 5.36 57.93 ± 5.04 62.13 ± 5.4 63.76 ± 5.46 65.54 ± 5.55 73.89 ± 5.7 CAT ME / L 228.36 ± 14.15 217.05 ± 13.85 226.12 ± 14.11 235.39 ± 14.38 249.98 ± 15.07 271.55 ± 16.3

table 2 Averaged laboratory indicators of endogenous intoxication and antioxidant protection in the studied patients with gangrenous form of acute cholecystitis with the use of ozone at a concentration of 0-10 mg / l in dynamics Indicators Registration Dates Before surgery 1 day post 3 days post 5 days p / o 7 day post Norm White blood cells (× 10 ⁹ / L) 9.27 ± 1.75 9.82 ± 1.88 8.79 ± 1.74 8.48 ± 1.67 7.83 ± 1.7 5.83 ± 1.34 Total bilirubin (μmol / L) 38.15 ± 10.55 34.67 ± 9.12 31.22 ± 8.8 28.21 ± 8.91 24.47 ± 7.99 13.78 ± 5.86 Indirect bilirubin (μmol / L) 25.09 ± 5.82 22.13 ± 4.76 17.45 ± 4.13 14.7 ± 4.18 11.38 ± 3.54 7.45 ± 2.61 LII (unit) 3.71 ± 0.95 4.09 ± 1.13 3.35 ± 0.8 2,52 ± 0,69 1.62 ± 0.38 0.73 ± 0.32 ACT (mmol / h * l) 0.54 ± 0.14 0.79 ± 0.18 0.63 ± 0.17 0.59 ± 0.13 0.46 ± 0.11 0.28 ± 0.07 Alt (mmol / h * l) 0.68 ± 0.14 1.62 ± 0.26 1.45 ± 0.24 1.12 ± 0.2 0.8 ± 0.15 0.46 ± 0.09 Total protein (g / l) 50, 29 ± 7.98 47.8 ± 7.14 51.87 ± 8.03 54.83 ± 8.25 56.82 ± 8.33 71.12 ± 12.84 Urea (mmol / L) 8.62 ± 2.1 8.9 ± 2.23 8.22 ± 1.94 7.68 ± 1.68 6.65 ± 1.42 5.32 ± 1.53 Blood Creatinine (mmol / L) 0.115 ± 0.032 0.117 ± 0.03 0.113 ± 0.025 0.11 ± 0.027 0.104 ± 0.022 0,083 ± 0,024 MDA (μmol / L) 49.93 ± 11.94 55.38 ± 13.26 51.26 ± 12.33 47.61 ± 11.75 42.02 ± 11.41 32.89 ± 8.43 MSM (c.u.) 0.25 ± 0.049 0.254 ± 0.051 0.248 ± 0.051 0.242 ± 0.044 0.235 ± 0.036 0.221 ± 0.03 DC (c.u. / ml) 34.72 ± 5.96 37.84 ± 6.62 35.9 ± 6.33 32.54 ± 5.77 26.03 ± 5.15 17.45 ± 3.23 SOD E / mg 60.34 ± 5.24 54.99 ± 4.81 58.48 ± 5.12 63.21 ± 5.44 68.42 ± 5.74 73.89 ± 5.7 CAT ME / L 219.62 ± 13.88 213.01 ± 13.76 228.2 ± 14.06 239.61 ± 14.42 255.98 ± 14.92 271.55 ± 16.3

Table 3 Averaged laboratory parameters of endogenous intoxication and antioxidant protection in the studied patients with gangrenous form of acute cholecystitis with the use of ozone in a concentration of 20-30 mg / l in dynamics Indicators Registration Dates Before surgery 1 day post 3 days post 5 days p / o 7 day post Norm White blood cells (× 10 ⁹ / L) 9.87 ± 1.72 10.5411.81 11.13 ± 2.13 9.5 ± 1.92 8.65 ± 1.76 5.83 ± 1.34 Total bilirubin (μmol / L) 41.18 ± 11.26 37.73 ± 9.85 36.81 ± 9.82 32.69 ± 8.49 28.95 ± 7.97 13.78 ± 5.86 Indirect bilirubin (μmol / L) 27.97 ± 6.32 24.56 ± 5.57 24.32 ± 5.55 20.54 ± 4.33 17.31 ± 4.08 7.45 ± 2.61 LII (unit) 3.26 ± 0.88 3.56 ± 0.95 5.33 ± 1.72 4.49 ± 1.24 3.75 ± 0.9 0.73 ± 0.32 ACT (mmol / h * l) 0.58 ± 0.16 0.95 ± 0.24 1.64 ± 0.41 1.39 ± 0.33 0.98 ± 0.25 0.28 ± 0.07 Alt (mmol / h * l) 0.69 ± 0.13 1.68 ± 0.29 1.79 ± 0.31 1.57 ± 0.24 1.13 ± 0.19 0.46 ± 0.09 Total protein (g / l) 52.01 ± 8.08 47.3 ± 7.31 41.68 ± 6.84 44.74 ± 7.02 46.95 ± 7.19 71.12 ± 12.84 Urea (mmol / L) 7.93 ± 1.89 8.62 ± 2.22 8.13 ± 2.13 7.94 ± 1.98 7.68 ± 1.81 5.32 ± 1.53 Blood Creatinine (mmol / L) 0.117 ± 0.026 0.121 ± 0.033 0.129 ± 0.031 0.119 ± 0.028 0.112 ± 0.027 0,083 ± 0,024 MDA (μmol / L) 46.26 ± 11.48 50.41 ± 12.18 64.08 ± 13.61 58.26 ± 13.45 55.62 ± 13.3 32.89 ± 8.43 MSM (c.u.) 0.248 ± 0.047 0.256 ± 0.055 0.27 ± 0.07 0.265 ± 0.064 0.251 ± 0.052 0.221 ± 0.03 DC (c.u. / ml) 35.22 ± 6.02 38.83 ± 6.98 43.51 ± 7.39 39.09 ± 7.07 35.65 ± 6.11 17.45 ± 3.23 SOD E / mg 55.08 ± 4.88 50.37 ± 4.42 44.2 ± 3.85 47.17 ± 4.02 52.85 ± 4.47 73.89 ± 5.7 CAT ME / L 222.72 ± 13.97 215.45 ± 13.8 195,93112,89 200.03 ± 12.95 204.16 ± 13.02 271.55 ± 16.3

Table 4 Averaged laboratory indicators of endogenous intoxication and antioxidant protection in the studied patients with gangrenous form of acute cholecystitis with the use of ozone at a concentration of 10-20 mg / l in dynamics Indicators Registration Dates Before surgery 1 day post 3 days post 5 days p / o 7 day post Norm White blood cells (× 10 ⁹ / L) 9.96 ± 1.74 10.37 ± 1.86 9.25 ± 1.65 8.02 ± 1.62 6.83 ± 1.71 5.83 ± 1.34 Total bilirubin (μmol / L) 40.06 ± 10.95 36.41 ± 9.28 24.49 ± 6.43 19.53 ± 5.02 16.72 ± 4.88 13.78 ± 5.86 Indirect bilirubin (μmol / L) 24.58 ± 5.48 22.69 ± 4.15 12.92 ± 2.97 9.44 ± 2.56 6.96 ± 2.48 7.45 ± 2.61 LII (unit) 3.18 ± 0.81 3.27 ± 0.94 2.11 ± 0.52 1.47 ± 0.37 0.8 ± 0.25 0.73 ± 0.32 ACT (mmol / h * l) 0.59 ± 0.18 0.63 ± 0.2 0.41 ± 0.15 0.35 ± 0.12 0.33 ± 0.09 0.28 ± 0.07 Alt (mmol / h * l) 0.66 ± 0.14 1.24 ± 0.22 0.89 ± 0.16 0.64 ± 0.12 0.42 ± 0.06 0.46 ± 0.09 Total protein (g / l) 53.45 ± 8.15 50.38 ± 7.85 57.04 ± 8.62 61.76 ± 8.69 65.24 ± 8.81 71.12 ± 12.84 Urea (mmol / L) 8.00 ± 1.92 8.42 ± 2.09 7.28 ± 1.71 6.6 ± 1.58 5.97 ± 1.43 5.32 ± 1.53 Blood Creatinine (mmol / L) 0.116 ± 0.025 0.119 ± 0.029 0.102 ± 0.02 0,091 ± 0,017 0.084 ± 0.015 0,083 ± 0,024 MDA (μmol / L) 48.83 ± 11.75 53.2 ± 13.08 42.72 ± 11.34 39.06 ± 10.97 35.58 ± 9.88 32.89 ± 8.43 MSM (c.u.) 0.255 ± 0.053 0.26 ± 0.06 0.244 ± 0.045 0.233 ± 0.034 0.226 ± 0.028 0.221 ± 0.03 DC (c.u. / ml) 34.18 ± 5.67 33.23 ± 5.49 28 ± 4,58 25.54 ± 4.07 21.91 ± 3.75 17.45 ± 3.23 SOD E / mg 58.15 ± 5.06 52.68 ± 4.39 69.31 ± 5.43 77.13 ± 5.98 85.76 ± 6.42 73.89 ± 5.7 CAT ME / L 220.51 ± 13.96 214.52 ± 13.81 244.65 ± 14.44 269.38 ± 15.33 285.19 ± 16.19 271.55116.3

Table 5 Averaged laboratory indicators of endogenous intoxication and antioxidant protection in comparative patients with a phlegmonous form of acute cholecystitis in dynamics Indicators Registration Dates Before surgery 1 day post 3 days post 5 days p / o Norm White blood cells (× 10 ⁹ / L) 8.92 ± 1.9 9.34 ± 1.88 8.59 ± 1.63 7.36 ± 1.68 5.83 ± 1.34 Total bilirubin (μmol / L) 29.15 ± 9.38 27.1 ± 9.01 22.32 ± 6.12 16.46 ± 4.2 13.78 ± 5.86 Indirect bilirubin (μmol / L) 16.29 ± 4.43 14.78 ± 4.26 10.58 ± 2.05 5.23 ± 1.13 7.45 ± 2.61 LII (unit) 1.83 ± 0.44 2.08 ± 0.52 1.97 ± 0.48 1.25 ± 0.33 0.73 ± 0.32 ACT (mmol / h * l) 0.46 ± 0.15 0.74 ± 0.19 0.51 ± 0.6 0.42 ± 0.13 0.28 ± 0.07 Alt (mmol / h * l) 0.7 ± 0.13 1.28 ± 0.25 0.72 ± 0.15 0.62 ± 0.12 0.46 ± 0.09 Total protein (g / l) 55, 62 ± 8.26 54.86 ± 8.25 58.19 ± 8.66 60.87 ± 8.73 71.12 ± 12.84 Urea (mmol / L) 7.42 ± 1.75 7.61 ± 1.86 6.81 ± 1.64 6.35 ± 1.59 5.32 ± 1.53 Blood Creatinine (mmol / L) 0.112 ± 0.026 0.114 ± 0.027 0.106 ± 0.022 0.089 ± 0.018 0,083 ± 0,024 MDA (μmol / L) 43.28 ± 11.5 46.04 ± 11.69 44.5 ± 11.61 41.91 ± 11.35 32.89 ± 8.43 MSM (c.u.) 0.244 ± 0.046 0.248 ± 0.047 0.237 ± 0.039 0.232 ± 0.034 0.221 ± 0.03 DC (c.u. / ml) 28.15 ± 4.77 30.08 ± 4.96 27.42 ± 4.63 22.64 ± 4.03 17.45 ± 3.23 SOD E / mg 62.3 ± 5.23 60.29 ± 5.12 64.75 ± 5.27 69.76 ± 5.41 73.89 ± 5.7 CAT ME / L 229.78 ± 13.95 225.35 ± 13.83 240.82 ± 14.35 253.91 ± 14.88 271.55 ± 16.3

Table 6 Averaged laboratory indicators of endogenous intoxication and antioxidant protection in the studied patients with the phlegmonous form of acute cholecystitis with the use of ozone at a concentration of 0-10 mg / l in dynamics Indicators Registration Dates Before surgery 1 day post 3 days post 5 days p / o Norm White blood cells (× 10 ⁹ / L) 8.04 ± 1.85 8.4 ± 1.8 8.05 ± 1.78 7.33 ± 1.76 5.83 ± 1.34 Total bilirubin (μmol / L) 33.14 ± 8.79 31.05 ± 8.18 24.63 ± 6.22 17.38 ± 3.65 13.78 ± 5.86 Indirect bilirubin (μmol / L) 20.47 ± 4.55 18.92 ± 4.04 13.81 ± 3.1 7.17 ± 1.72 7.45 ± 2.61 LII (unit) 1.3 ± 0.39 1.72 ± 0.47 1.62 ± 0.46 1.08 ± 0.36 0.73 ± 0.32 ACT (mmol / h * l) 0.43 ± 0.17 0.69 ± 0.22 0.46 ± 0.16 0.35 ± 0.11 0.28 ± 0.07 Alt (mmol / h * l) 0.72 ± 0.13 1.25 ± 0.24 0.77 ± 0.14 0.59 ± 0.1 0.46 ± 0.09 Total protein (g / l) 57.13 ± 8.64 56.98 ± 8.6 59.29 ± 8.7 63.47 ± 8.86 71.12 ± 12.84 Urea (mmol / L) 7.26 ± 1.66 7.42 ± 1.72 6.79 ± 1.6 6.45 ± 1.58 5.32 ± 1.53 Blood Creatinine (mmol / L) 0.11 ± 0.024 0.113 ± 0.025 0.107 ± 0.0121 0.096 ± 0.019 0,083 ± 0,024 MDA (μmol / L) 44.17 ± 11.68 46.01 ± 11.74 45.73 ± 11.7 40.36 ± 11.49 32.89 ± 8.43 MSM (c.u.) 0.239 ± 0.038 0.243 ± 0.045 0.24 ± 0.043 0.234 ± 0.036 0.221 ± 0.03 DC (c.u. / ml) 30.64 ± 5.18 33.12 ± 5.59 31.95 ± 5.26 23.82 ± 4.22 17.45 ± 3.23 SOD E / mg 64.57 ± 5.29 61.27 ± 5.15 66.14 ± 5.36 72.41 ± 5.66 73.89 ± 5.7 CAT ME / L 223.88 ± 13.79 220.06 ± 13.65 234.58 ± 14.17 246.14 ± 14.68 271.55 ± 16.3

Table 7 Averaged laboratory indicators of endogenous intoxication and antioxidant protection in the studied patients with the phlegmonous form of acute cholecystitis with the use of ozone at a concentration of 20-30 mg / l in dynamics Indicators Registration Dates Before surgery 1 day post 3 days post 5 days p / o Norm White blood cells (× 10 ⁹ / L) 8.44 ± 1.94 8.67 ± 1.98 9.11 ± 1.95 7.8 ± 1.79 5.83 ± 1.34 Total bilirubin (μmol / L) 34.84 ± 9.11 30.05 ± 8.89 27.63 ± 8.35 24.38 ± 7.68 13.78 ± 5.86 Indirect bilirubin (μmol / L) 22.47 ± 4.32 18.5 ± 4.18 16.81 ± 3.85 13.89 ± 3.2 7.45 ± 2.61 LII (unit) 1.51 ± 0.4 1.88 ± 0.54 2.29 ± 0.72 1.79 ± 0.49 0.73 ± 0.32 ACT (mmol / h * l) 0.48 ± 0.13 0.72 ± 0.16 0.86 ± 0.18 0.54 ± 0.15 0.28 ± 0.07 Alt (mmol / h * l) 0.65 ± 0.13 1.03 ± 0.2 1.4 ± 0.26 0.76 ± 0.13 0.46 ± 0.09 Total protein (g / l) 56.13 ± 8.55 54.98 ± 8.47 50.29 ± 8.32 52.47 ± 8.33 71.12 ± 12.84 Urea (mmol / L) 7.31 ± 1.7 7.64 ± 1.88 8.2 ± 2.01 7.35 ± 1.68 5.32 ± 1.53 Blood Creatinine (mmol / L) 0.109 ± 0.02 0.112 ± 0.018 0.114 ± 0.025 0.108 ± 0.021 0,083 ± 0,024 MDA (μmol / L) 46.4 ± 11.81 48.62 ± 11.99 50.18 ± 12.15 45.29 ± 11.72 32.89 ± 8.43 MSM (c.u.) 0.246 ± 0.05 0.249 ± 0.054 0.252 ± 0.058 0.247 ± 0.02 0.221 ± 0.03 DC (c.u. / ml) 27.97 ± 4.88 30.45 ± 5.01 32.16 ± 5.37 28.81 ± 4.62 17.45 ± 3.23 SOD E / mg 61.77 ± 5.13 59.44 ± 4.99 57.21 ± 4.82 64.1 ± 5.32 73.89 ± 5.7 CAT ME / L 230.08 ± 13.99 227.49 ± 13.86 221.13 ± 13.74 232.7 ± 14.08 271.55 ± 16.3

Table 8 Averaged laboratory indicators of endogenous intoxication and antioxidant protection in the studied patients with the phlegmonous form of acute cholecystitis with the use of ozone at a concentration of 10-20 mg / l in dynamics Indicators Registration Dates Before surgery 1 day post 3 days post 5 days p / o Norm White blood cells (× 10 ⁹ / L) 8.49 ± 1.95 8.61 ± 1.96 7.92 ± 1.82 7.35 ± 1.73 5.83 ± 1.34 Total bilirubin (μmol / L) 36.03 ± 10.15 32.76 ± 8.57 23.9 ± 6.16 15.51 ± 3.84 13.78 ± 5.86 Indirect bilirubin (μmol / L) 25.09 ± 6.36 22.68 ± 5.9 15 ± 4.71 7.13 ± 3.06 7.45 ± 2.61 LII (unit) 1.63 ± 0.46 1.89 ± 0.58 1.36 ± 0.38 0.55 ± 0.18 0.73 ± 0.32 ACT (mmol / h * l) 0.45 ± 0.13 0.66 ± 0.16 0.35 ± 0.1 0.28 ± 0.05 0.28 ± 0.07 Alt (mmol / h * l) 0.67 ± 0.12 1.3 ± 0.22 0.64 ± 0.11 0.49 ± 0.07 0.46 ± 0.09 Total protein (g / l) 57.05 ± 8.6 56.13 ± 8.52 64.42 ± 8.91 69.32 ± 9.17 71.12 ± 12.84 Urea (mmol / L) 7.71 ± 1.95 8.18 ± 2.05 6.58 ± 1.67 5.13 ± 1.39 5.32 ± 1.53 Blood Creatinine (mmol / L) 0.114 ± 0.021 0.116 ± 0.024 0.105 ± 0.015 0.085 ± 0.09 0,083 ± 0,024 MDA (μmol / L) 45.19 ± 11.74 49.32 ± 12.01 42.071 ± 1.38 36.25 ± 9.52 32.89 ± 8.43 MSM (c.u.) 0.24 ± 0.041 0.242 ± 0.044 0.23 ± 0.034 0.222 ± 0.027 0.22 ± 10.03 DC (c.u. / ml) 25.45 ± 4.6 29.26 ± 5.12 22.18 ± 3.95 15.87 ± 2.88 17.45 ± 3.23 SOD E / mg 57.43 ± 4.85 55.05 ± 4.76 76.9 ± 5.61 88.64 ± 6.48 73.89 ± 5.7 CAT ME / L 228.46 ± 13.93 225.11 ± 13.81 262.89 ± 14.9 299.02 ± 16.82 271.55 ± 16.3

As a result, the analysis of the results of clinical and laboratory studies showed the optimal value of the concentration of a fixed volume of medical ozone for postoperative decontamination of the surgical intervention area for a given nosology, equal to 10-20 mg / l. It is this concentration of ozone in the gas mixture that combines the signs of maximum efficiency compared to traditional treatment and safety for the patient with all forms of destructive cholecystitis. And it was also established the positive effect of local ozone therapy on free radical processes in the body through moderate stimulation of antioxidant systems.

Thus, the proposed method allows to reduce the number of purulent-septic complications in the postoperative period, to reduce the general intoxication of the body and to reduce the length of the patient’s hospital stay.

Example: Patient Sh., 60 years old, East. bol. No. 127, was admitted urgently to the 1st surgical department of Clinical Hospital No. 7 of Krasnoyarsk on 01/09/2009 at 13.25. with a diagnosis of acute cholecystitis. Upon admission, the patient complained of periodic, paroxysmal, sharp pain in the right hypochondrium, nausea, repeated vomiting of gastric contents and bile, which did not bring relief, dry mouth, general weakness, malaise, slight chills. He considers himself sick about 17 hours, when heavy consumption of fatty and spicy foods provoked an attack of biliary colic. Such attacks appeared about a year ago, with time becoming more frequent, lengthened and heavier at the clinic, however, the patient did not go to the doctor, continued to not follow the diet, was treated with single doses of antispasmodic and painkillers. During the last attack, self-administration of drugs did not give sufficient effect, the patient turned to the clinic, from where she was sent to a surgical hospital. Objective status: patient’s condition upon receipt of moderate severity, the skin is moderately pale, sclera subicteric, no swelling, the temperature in the armpit is 37.3 ° C. In the lungs, breathing in all fields is harsh, there is no wheezing, crepitus, NPV 18 / min, heart sounds are deaf, rhythmic, noises are not heard, heart rate 88 beats / min, pulse 88 / min, rhythmic, not strained, satisfactory filling, BP 145 / 95 mmHg The tongue is dry, densely coated with a white coating. The abdomen is swollen, symmetrical, participates in the act of breathing, tense and painful in the epigastrium and the right hypochondrium, tympanitis in all parts of the abdomen, there is no blunting of percussion sound in the flat parts of the abdomen, intestinal sounds are audible. Revealed moderately positive symptoms of Ortner, Kera, Musset. Symptom Shchetkina-Blumberg negative. The lower edge of the liver is palpatory sharp, even, elastic, extends 1.5 cm from under the edge of the costal arch. With percussion, the size of the liver according to Kurlov: on the right midclavicular line - 13 cm, on the front median line - 11 cm, on the left costal arch - 9 cm. The kidneys are not palpable, Pasternatsky’s symptom is negative on both sides, urination is painless. Blood tests showed moderate leukocytosis (15.1 * 10 ⁹ / L), an increase in the erythrocyte sedimentation rate (ESR) (24 mm / h), an increase in the leukocyte intoxication index (LII) (1.65 units), hyperbilirubinemia (total bilirubin - 19.5 μmol / l, direct bilirubin - 5.4 μmol / l, indirect bilirubin - 14.1 μmol / l), an increase in blood transaminases (ACT - 0.46 mmol / h * l, ALT - 0.66 mmol / h * l), an increase in urea (7.83 mmol / L), creatinine (0.115 mmol / L), malondialdehyde (MDA) (44.85 mmol / L), molecules of average molecular weight (MSM) (0.242 oz. e.), diene conjugates (DC) (24.76 cu / ml), decreased total protein (55.94 g / l), superoxide dismutase (SOD) (56.55 U / mg) and catalase (CAT) (230.17 mU / l). The patient was prescribed conservative treatment, including infusion therapy (Salnikov's mixture), the use of anticholinergics (platifillin), antibacterial therapy (ceftriaxone). During the day, the patient's condition improved, pain and nausea decreased, vomiting did not recur. Ultrasound of the abdominal cavity from 01/10/2009: the gallbladder is enlarged, large single stones are located in its lumen up to 2-3 cm in diameter. The common bile duct is not expanded, it does not contain calculi. Conclusion: Gallstone disease (cholelithiasis). As a result, the patient was offered planned cholecystectomy from "mini-access", consent was obtained. 12.01.2009, at 10.30-12.00 performed cholecystectomy, drainage of the subhepatic space. After operative access, an enlarged, phlegmonous-changed gall bladder with palpable calculi in its lumen was detected. A cholecystectomy from the neck was performed, hemostasis of the hepatic bed was performed, the subhepatic space was drained with 2 polyvinyl chloride drainages, the abdominal cavity was sutured in layers. In the postoperative period, along with traditional treatment with infusion (Salnikov’s mixture), anti-inflammatory (acetylsalicylic acid), antibacterial (ceftriaxone) therapy, antispasmodics (papaverine), analgesics (ketonal), physiotherapy and diet therapy, local ozone was started from 2 days ago space, which was prescribed 1 time per day and was carried out daily for 4 days until the drainage was removed, introducing 100 ml of an ozone-oxygen mixture with an ozone concentration of 10-20 mg / l. The reason for the end of the drainage was the absence of discharge from the drainage tubes. In blood tests 01/17/2009: leukocytes - 7.2 * 10 ⁹ / l, ESR - 12 mm / h, total bilirubin - 12.6 μmol / l, direct bilirubin - 3.8 μmol / l, indirect bilirubin - 8.8 μmol / L, ACT 0.29 mmol / h * L, ALT 0.51 mmol / h * L, total protein 71.48 g / L, urea 5.15 mmol / L, creatinine 0.083 mmol / L, MDA - 33.79 μmol / L, MSM - 0.223 cu, DK - 15.43 cu / ml, SOD - 90.06 U / mg and CAT - 302.11 mU / l Microbiologically, on January 15, 2009, cultures of Escherichia coli, Klebsiella pneumonia, Streptococcus pyogenes and Pseudomonas aeruginosa were found in the wash water, and the wash water was sterile on January 17, 2009. In the postoperative period, purulent complications were not detected, the pain syndrome was stopped on the 3rd day, the temperature returned to normal on the 5th day, the postoperative wound healed per prima, and the sutures were removed on the 6th day. On the 7th day after the operation, the patient was discharged from the hospital in satisfactory condition.

The advantage of the proposed method compared to the known ones is the absence of gas hypertension in the abdominal cavity due to the possibility of an outflow of the ozone-oxygen mixture and a small volume of introduced ozone, as well as a decrease in the number of purulent-septic complications after operations on the gallbladder and / or biliary tract due to an increase in the frequency ozonation sessions, which enhances the effectiveness of postoperative therapy and reduces the effects of general intoxication.

Claims (1)

A method of local dosed ozone therapy after operations on the gallbladder and / or biliary tract, including insufflation of the ozone-oxygen mixture, characterized in that at the final stage of the operation two polyvinyl chloride drainage tubes are installed in the subhepatic space through a counter-opening, communicating with each other via the subhepatic space from the second day of the postoperative period until the drainage tubes are removed, 80-120 ml of ozone-oxygen are injected daily into the delivery tube a mixture with an ozone concentration of 10-20 mg / l at a rate of 2 ml / s using a disposable Janet syringe with a volume of 150 ml, while with the introduction of the first 60-80 ml of ozone-oxygen mixture, the lumen of the outlet tube is closed with a clamp, and the remaining 20-40 ml are introduced with an open outlet pipe after a 2-3-minute pause.