RU2249451C2 - Method for treating acute purulent inflammation in serous cavity - Google Patents

Abstract

FIELD: medicine.

SUBSTANCE: method involves introducing perfluoran bubbled with ozone-and-oxygen mixture with given ozone concentration of 3000 mkg/l during 15 min.

EFFECT: restricted peritoneal inflammation.

Description

The invention relates to medicine, namely to surgery, and is intended for the treatment of acute purulent inflammation in the serous cavity.

It is known that for the treatment of purulent peritonitis in the clinic and experiment, the Perftoran blood substitute is used, which is considered a multifunctional drug (G.R. Askerkhanov, A.M. Golubev, A.G. Huseynov, V.V. Moroz and U.Z. Zagirov, 2000; PMRagimov, A.M. Golubev, A.O. Osmanov, A.S. Alkadarsky, M.-E. A. Askerov, 2001, etc.). The effect in this case, as the authors point out, is achieved by activating the system of phagocytic cells of the peritoneal fluid and stimulating the immunocompetent organs, as well as, to a certain extent, the cytoprotective, membrane-stabilizing and sorption properties of perftoran.

It is also known that ozone therapy is used as an effective method of sanitation of the peritoneal cavity in experimental peritonitis and for treatment in patients with diseases of the abdominal cavity complicated by peritonitis (I.A. Karabelnikov and S.V. Aksenova, 1997; S.V. Aksenova and co-authors, 2000; N.Yu. Veksler and co-authors, 2000, etc.).

In particular, the proposed “Intraperitoneal perfusion of perftoran in the treatment of patients with advanced purulent peritonitis” proposed by G.R. Askerkhanov et al. (Administration of 100-150 ml of perftoran in the peritoneal cavity before wound closure), according to the authors, reduces the need for repeated sanitation of the peritoneal cavity by 44 % and mortality - by 5.2%, and that 48 hours after the initial treatment in patients treated with perfluorane, the number of aerobic microorganisms is reduced by 2 times compared with the control, new fibrin overlay from 85, 0 to 33, 3% and nearly anaerobes disappear ("Surgery", 2000, No. 9. - p. 8-10).

The disadvantage of this treatment method is that perftoran injected into the peritoneal cavity pours out through the drainage tubes after 2 hours, possibly slightly increasing the migration of macrophages and adsorbing part of the toxins. At the same time, the effect of perfluoran itself is limited in time and only a small part of it is absorbed from the peritoneal cavity, which cannot have a significant cytoprotective and membrane-stabilizing effect on tissue cells damaged by toxins.

In addition, perfluoran does not have antiseptic properties, and therefore there is a need for preliminary sanitation by traditional methods.

A PROTOTYPE of the proposed method of treatment is “Ozone therapy of widespread peritonitis in the early postoperative period” (B. P. Kudryavtsev et al., “Surgery”, 1997, No. 3 - p. 36-41).

In order to study the effectiveness of the use of ozone-containing drugs for the treatment of common purulent peritonitis, the authors created its model in 40 laboratory animals (white rats with a body weight of 180-200 g).

After the development of peritonitis, as judged by clinical manifestations, all animals were divided into two groups (20 individuals each) - control and main. The treatment of experimental peritonitis was carried out according to the following method: at the height of clinical manifestations, on average 24 hours after the initiation of peritonitis, under a ether anesthesia, a single washing abdominal sanitation was performed using a puncture method (in animals of the main group, a freshly prepared solution of furatsilin 1: 5000 saturated immediately before using an ozone-oxygen gas mixture with an ozone concentration of 4-6 μg / l in a volume of 0.7 ml per 1 g of body weight) to clean wash water, after which the animals were injected into neck cavity and rectally 1 cm ^{3 of} ozone-oxygen gas mixture at the rate of 0.048 μg of ozone per 1 g of body weight. Subsequently, twice with an interval of 12 hours, the administration was repeated, replacing the intraperitoneal injection of gas with ozonized physiological solution (0.9% sodium chloride solution) with the same concentration of ozone. In animals of the control group, for the sanitation of the abdominal cavity, the authors used a solution of furatsilin 1: 5000, not oxygenated, but treated with oxygen with the same exposure, and then oxygen and physiological solution in the same volume as in animals of the main group. During treatment, twice when animals were removed from the experiment (within 24 and 48 hours from the initiation of peritonitis), the number of microorganisms in the internal organs (in the liver and heart) was determined. Moreover, in animals of the main group, after 24 hours from the start of treatment, a significant decrease (up to single colonies) of the level of microbial contamination of the internal organs was noted, while in animals of the control group it remained the same. In rats of both groups, 2 hours after the start of treatment, a decrease in the number of leukocytes was recorded mainly due to lymphocytes (in animals of the control group - by 21.2%). A similar reaction characteristic of stress, as the authors indicate, was less pronounced with ozone therapy. After 24 hours from the start of treatment in animals of the main group, according to their data, there was a significant decrease in the blood leukocyte count due to all forms, including stab forms, while in animals of the control group, expressed leukocytosis and a characteristic stab shift were preserved in the blood .

Prototype criticism

1. Ozonation of an aqueous solution of furatsilina. Studies conducted by employees of the Department of General Surgery of the Faculty of Medicine of the Russian State Medical University and the City Clinical Hospital No. 13 of Moscow (L. Laberko et al., 2000) show the inexpediency of ozonation of solutions of antiseptics: furatsilina, rivanol, chlorhexidine, dioxidine due to their change physical and chemical properties and blockade of their antibacterial action.

2. The use of very small volumes of ozonized solution - 1 cm ³ , where the concentration and amount of dissolved ozone are negligible.

3. Multi-stage treatment procedures (ineffective, taking into account the studies of L. A. Laberko et al., Flushing sanitation with an ozonated solution of furatsilin, intraperitoneal and rectal insufflation of the ozone-oxygen mixture, followed by two injections of ozonized physiological solution into the peritoneal cavity.

4. In the prototype there are no indicators of survival of animals in the control and main groups; the studies were carried out during the first 2 days, in connection with which the long-term result was not traced, respectively, the adhesion process, which is usually a complication of purulent inflammation of the peritoneum.

Thus, there is no information in the literature on the possibility of using ozonated perfluorane, although there is evidence of high solubility and stability of ozone in organofluorine compounds, in particular, in Perfluorodicaline (S. D. Razumovsky and V. V. Podmasteriev, 2000).

The aim of the present invention is to develop a method for the treatment of acute purulent inflammation in the serous cavity.

The goal is realized by the sanitation of the infected serous cavity by sparging with an ozone-oxygen mixture of perfluorane with a given ozone concentration of 3000 μg / l for 15 minutes.

The ozonizer “Medozons - BM AOT-N-01-Arz-91” (firms of the OJSC “Arzamassky Instrument-Making Plant”) was used to bubble perftoran.

SUMMARY OF THE INVENTION

Proposed as an invention, the method is as follows.

Against the background of acute purulent inflammation in the serous cavity, it is sanitized with ozone-ozonated for 15 minutes (sparging) with an ozone-oxygen mixture of perfluorane with a given ozone concentration of 3000 μg / l.

In acute peritonitis, for intraperitoneal administration of ozonized perfluorane, the rat is lowered upside down under chloroform anesthesia or in N.I. Lozhkin's fixative (1971). The skin of the abdomen, caudal to the navel, is taken into the fold, the abdominal wall is punctured perpendicularly, then a needle is inserted in the direction of the fold (in order to avoid damage to the needle of the internal organs).

It is proposed for the treatment of acute experimental fecal peritonitis in white rats to use 2.5-3.5 ml of ozonated perftoran at the rate of 1.5 ml per 100 g of animal weight.

The use of ozonized perftoran in the specified amount provides for the rehabilitation of the peritoneal cavity in acute fecal peritonitis.

Depending on the severity of the inflammatory process and the timing of peritonitis, the procedure can be repeated, but not earlier than 48 hours.

The developed method of treatment at a later date (24 hours or more) of the development of peritonitis can be recommended in combination with antibacterial therapy.

The developed method can be used in acute purulent inflammation in the serous cavities of various locations (acute purulent pleurisy, arthritis, peritonitis).

COMPARATIVE ANALYSIS OF THE SIGNS OF THE PROTOTYPE AND THE PROPOSED INVENTION

In the proposed method, perfluorane is used as a medium for dissolving the ozone-oxygen mixture, in which ozone is more soluble and stable than in physiological saline. According to the prototype method, physiological saline is used as a medium for dissolving the ozone-oxygen mixture.

EXAMPLE OF SPECIFIC PERFORMANCE

Extract from the laboratory journal of the Department of Human Anatomy.

To study the effectiveness of the use of ozonated perftoran for the treatment of acute purulent inflammation in the serous cavity, a model of acute fecal peritonitis was created according to the Remmenik method (1965) by introducing 5% fecal suspension in physiological solution at the rate of 1 ml per 100 g of animal weight in 72 white rats weighing 140- 160 g

The experiments were conducted on the basis of the sanatorium “Kpul-Yatar” of the Republic of Dagestan on April 20 and 21, 2002.

Perfluorane or physiological saline was ozonized by ozonation with an ozone-oxygen mixture in the laboratory of the sanatorium on the ozonator “Medozons - BM AOT-N-01-Arz-91” (the company Arzamassky Instrument-Making Plant OJSC).

04/20/02, Under chloroform anesthesia, a 5% fecal suspension was introduced into the peritoneal cavity, after which the rats were divided into separate cells in series:

I series (12 rats) 5% fecal suspension and physiological saline solution were introduced into the peritoneal cavity.

II series (12 rats). An ozonized physiological solution was introduced into the peritoneal cavity immediately after injection of fecal suspension (1 control group).

III series (12 rats). Ozonized perfluorane was introduced into the peritoneal cavity immediately after injection of fecal suspension (1 main group) on April 21, 02

IV series (12 rats). An ozonized physiological solution was injected into the peritoneal cavity against the background of developing 24-hour fecal peritonitis (2 control groups).

V series (12 rats). Ozonated perfluorane was injected into the peritoneal cavity against the background of developing 24-hour fecal peritonitis (2 main group).

Saline or perfluorane was injected into the peritoneal cavity at the rate of 1.5 ml per 100 g of animal mass.

On the same day, i.e. 04.21.02, under chloroform anesthesia, 3 rats from series I, II, and III were withdrawn from the experiment.

Autopsy of the abdominal and thoracic cavities took fingerprints, then a thorough examination was performed, and then the mesenteric lymph nodes, sections of the jejunum and ileum with lymphoid nodules and the spleen were removed for histopathological examination. All material is fixed in 10% neutral formalin.

On the same day, the remaining rats (I-V series) in separate cages were taken to the vivarium of the Department of Human Anatomy of the Daggosmedakademii.

From April 22, 02 to April 28, 02, i.e. after 24, 48, 72 hours, 7 days, the remaining rats were also withdrawn from the experiment, as described above.

Smears-prints from the pleural and peritoneal cavities and blood from the right ventricle of the heart are stained according to Romanovsky - Giemsa for cytological examination.

The histological material was examined after appropriate wiring, pouring into blocks, preparing sections and staining them with hematoxylin-eosin, according to Romanovsky - Giemsa with methyl green and pironin, and sections of the small intestine with an additional alcian blue.

A comparative analysis of the experimental results showed:

1. In the case of intraperitoneal administration of non-zoned physiological saline solution with fecal suspension, a pattern of diffuse peritonitis develops, and all rats die on the 4-7th day of peritonitis.

2. With the introduction of ozonized physiological saline immediately after intraperitoneal injection of fecal suspension, the phenomena of diffuse peritonitis are less pronounced; in most rats, peritonitis is limited to the appearance of fibrin plaque, minor adhesions and 2-3 pustules abscesses between the loops of the intestines and on the lower surface of the liver on the 2nd and subsequent days. The survival of rats at 4-7 days is about 83%. In smears from the peritoneal cavity, single microbes, many white blood cells and macrophages are noted.

3. With the introduction of ozonized perftoran immediately after the introduction of fecal suspension, diffuse peritonitis in rats practically does not develop, limiting on the 2nd and last day by examination in the form of insignificant 1-2 small round formations in the gland folds without adhesions. In this case, the survival rate of rats is 100%. There is no free flora in fingerprints; there are foamy macrophages and white blood cells.

4. If ozonized physiological saline is introduced on the next day, i.e. 24 hours after injection of fecal suspension, a developed picture of diffuse peritonitis in most rats develops; 50% of them die on the 4-7th day. The rheological properties and blood coagulability are impaired (with decapitation by chloroform anesthesia, about 1-2 ml of dark quick-coagulate blood flows).

In smears from the peritoneal cavity and pleural sinuses, free coccal flora and Escherichia coli are noted.

5. If ozonated perfluorane is introduced on the next day, i.e. 24 hours after an intraperitoneal injection of fecal suspension, a pattern of diffuse peritonitis was recorded in approximately 17% of the animals. In another 17% of the animals, small clumped abscesses between the folds of the omentum, adhesions or not at all are found on 2-3 days or they are very tender, easily destroyed when the intestinal loops move. In the remaining 66% of the animals, fibrin plaque on the peritoneum is not determined, pleural sinuses without features. In smears, fingerprints, the microbial flora is not detected; cell density is much lower, but among them the overwhelming majority are macrophages with foamy cytoplasm (“perfluorophages”) and monocytes. The survival rate of animals is about 83% (1 rat died on 3 and another one on the 5th day of peritonitis).

USEFULNESS OF THE INVENTION

The result of the obvious positive effect of ozonized perftoran and its advantages over ozonized saline for the treatment of acute fecal peritonitis is confirmed not only by the dynamics of peritonitis, but also by the results of cytological and histological studies of the material taken.

The method was tested twice on white rats with acute experimental fecal peritonitis.

Perftoran, unlike saline, has sorption, cytoprotective and membrane stabilizing properties. (Khrupkin V.I., Moroz V.V., Pisarenko L.V., Khomenchuk A.I., 1997).

Perftoran stimulates the system of peritoneal monocytic phagocytes and regional immune organs, i.e. the first line of antimicrobial protection of the peritoneal cavity with peritonitis (Askerkhanov G.R. et al., 2000; Ragimov P.M. et al., 2001).

Perftoran improves hemorheology, microcirculation (Ragimova D.M., 1999), is also a good carrier of oxygen and carbon dioxide.

The ozone-oxygen mixture, “dissolved” in perfluorane, has a more prolonged effect (in physiological saline, ozone decays rapidly, after 30 minutes its concentration decreases by 50% or more (Pyatayev N.A. et al., 2000).

Ozonated perfluorane is most effective in the first hours of peritonitis, which can prevent the spread of inflammation along the peritoneum, even with a single intraperitoneal injection.

Ozonated perfluorane also delays the development of purulent pleurisy, which in almost 34% of cases is observed in rats on fecal peritonitis 2-3 days after treatment with ozonized saline and in 83% without treatment.

Claims (1)

A method for the treatment of acute purulent inflammation in the serous cavity, which consists in sanitizing this cavity with an ozone-oxygen mixture with perfluorane bubbled for 15 minutes with a predetermined ozone concentration of 3000 μg / L.