RU2363476C1 - Way preventing postoperative adhesions formation - Google Patents

Abstract

FIELD: medicine.

SUBSTANCE: invention concerns medicine, namely, to abdominal surgery, and can be used for prevention of formation of postoperative adhesions of serous cavities. For this purpose deserosed and-or the inflamed sites of organs and a cavity wall are covered with an admixture of sterile gel "Lintexum-Mesogel" and derinate during an operative measure on organs of serous cavities. Derinate volume makes from 1% to 25% from all volume of the admixture. The way allows preventing development of adherent process in abdominal cavity in the postoperative period without additional administration of other medicinal preparations during this period at the expense of local prolonged immunopotentiation provision and consolidation prevention of deserosed surfaces.

EFFECT: prevention of development of adherent process in abdominal cavity in the postoperative period without additional administration of other medicinal preparations during this period at the expense of local prolonged immunopotentiation provision and consolidation prevention of deserosed surfaces.

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Description

The invention relates to medicine, in particular to abdominal surgery, and can be used in surgical operations on organs located in serous cavities, for example, on abdominal organs.

Closest to the claimed solution is a method of local immunotherapy with the myelopid preparation described by B.C. Antsupova “The effectiveness of local immunocorrection in the complex treatment of adhesions of the pelvic organs” (Dis. Candidate of Medical Sciences. Orel, 2006), which consists in irrigation of the pelvic organs with a solution of the drug Mielopid in a dose of 60 mg per 20 ml of saline solution the time of surgery with repeated administration through a modified microirrigator 24 and 48 hours after surgery at a dose of 30 μg / ml (3 mg per 100.0 ml of 0.9% sodium chloride solution).

The main disadvantages of this method is, firstly, that a Mielopid solution having a liquid consistency is rapidly absorbed from the abdominal cavity, which requires additional administration of the drug in the postoperative period, and secondly, there is no barrier effect from the introduction of the drug, and thirdly, the implementation of the method involves the introduction into the abdominal cavity of a foreign body - a microirrigator, which can even increase the severity of intraperitoneal adhesion.

The objective of the invention is the creation of a method of local prolonged immunoprophylaxis of the cavity adhesions, which allows to do without additional administration of the drug in the postoperative period by increasing the length of his stay between the wound surfaces with the aim of primary and secondary (anti-relapse) prevention of adhesions.

The task is achieved in that during surgery, those areas in which there is a high likelihood of adhesions (deserted areas, areas of superimposed anastomoses, areas with signs of inflammation, etc.) are treated with a bio-soluble inert absorbable gel with an immunomodulator deposited in it. .

The method is as follows.

During abdominal, e.g. laparotomic or laparoscopic surgery, and / or before closing of the serous cavity at the last stage of the intervention, those areas in which there is a high probability of primary or recurrent development of adhesions (e.g., deserted areas, areas of superimposed anastomoses, areas of obvious or probable inflammation, areas of injury after dissection of adhesions, drying of the peritoneum, etc.) are treated with a sterile gel with an immunomodulator deposited in it. The combination of the immunomodulator solution and the polymer gel is achieved by their extemporaneous, immediately before use, mixing in the required proportions until uniform, while the ratio of the volumes of the gel and the solution of the immunomodulating drug should be such that the solution introduced into the system does not exceed 25% of the total volume, since more liquid will reduce the viscosity of the gel, and accordingly, its anti-adhesive properties. The gel is prophylactically applied to the serous cover with a syringe or squeezed out of the container in which it was mixed onto the surgeon’s hand and applied with lubricating movements to a devoid peritoneum, deserted surface and places where adhesions can form (signs of inflammation or ischemia: swelling, hyperemia, vasodilation, discoloration, peristalsis, decreased pulsation of the abdominal vessels, etc.). In diffuse processes (for example, after sanitation of the abdominal cavity in patients with advanced peritonitis), a gel with an immunomodulator is administered in a dose calculated according to table D. DiZerega (1999), for humans - 2.4 ml / kg, for animals (rats) - 10.7 ml / kg. When carrying out operations under laparoscopic approaches, manipulators-injectors are used to introduce a gel with an immunomodulator deposited in it.

Concrete example

As a prophylactic, we used a mixture of the Lintex-Mesogel resorbable sterile gel and the Derinat immunomodulator at a dose of 1.5 mg per 1 kg of weight (according to the instructions for the drug).

Lintex-Mesogel is a 4% aqueous solution of sodium salt of carboxymethyl cellulose manufactured by Lintex LLC (St. Petersburg), non-toxic, sterile, designed to prevent adhesions after operations on organs and tissues with a serous coating (registration certificate No. FS 01262006 / 3224-06 from 04/25/2006 to 04/25/2011; certificate of conformity N ROSS RU.IMO9.B01505 from 05/17/2006 to 05/17/2009).

Derinat - sodium deoxyribonucleate, a clear, colorless liquid - extract from sturgeon milk. Pharmacological action: immunomodulatory, stimulation of regeneration and hematopoiesis, wound healing, anti-inflammatory, antitumor. The gel and the preparation were mixed in a sterile container in the ratio necessary to achieve an effective concentration of Derinat in the base (0.2 ml of Derinat solution per 2 ml of gel).

The experiments were carried out on healthy sexually mature male Wistar rats weighing 250-300 g. The studies were carried out in compliance with the principles set forth in the Convention for the Protection of Vertebrate Animals used for experimental and other purposes (Strasbourg, France, 1986).

The method was tested on the model of the adhesive process of the abdominal cavity (SPBP) (Lipatov V.A. et al., 2004): after the mid-laparotomy incision, the hydraulic dissection of the peritoneum of the ventral wall was performed with its subsequent excision on an area of 1 × 1 cm, 1 cm from the edge the middle wound, the cecum was subjected to scarification on the entire surface until the appearance of "bloody dew".

The animals were divided into four series, 15 animals each. The first series was a control - only the SPBP model, after the SPBP model, the damaged peritoneal sections were treated with Lintex-Mesogel anti-adhesive gel, the third series with Derinat solution, the fourth with Lintex-Mesogel anti-adhesive gel with Derinat deposited in it. Animals were withdrawn from the experiment on day 14 by overdose of ether anesthesia. Rats underwent autopsy, a thorough study of the abdominal organs with an assessment of the severity of the adhesive process visually and using the technique of semantic differential (a scoring system consisting in assessing the prevalence of the adhesion process, deformation of the abdominal cavity and the severity of individual types of adhesions, taking into account the significance coefficient of each indicator). The parietal peritoneum and organs of the abdominal cavity were subjected to histological examination according to the generally accepted method with fixation in neutral formalin, paraffin embedding, hematoxylin-eosin staining of the sections, silver foot impregnation and staining using the SIC reaction. Cytological studies - smears of the peritoneum were stained according to Romanovsky. Micropreparations were studied by light microscopy. Microphotography was carried out with the subsequent determination of regenerative indicators (karyocytoplasmic index (ratio of the diameters and volumes of the nucleus and cytoplasm), the number of mitoses, etc.). The results of macro- and micromorphological studies are shown in tables 1, 2.

Table 1 EXPRESSION OF THE ADHESIVE PROCESS OF THE ABDOMINAL CAVITY IN ANIMALS FOR 14 DAYS AFTER MODELING OF SPBP Series Number of living No. of living with SPBP, abs. Number of living with SPBP,% The severity of SPP, m R 1. Model (control) fifteen fifteen one hundred 1.87 ± 0.16 - 2. Model SPBP + gel fifteen eleven 73.3 0.65 ± 0.19 <0.05 * 3. Model SPBP + Derinat fifteen fifteen one hundred 1.54 ± 0.17 > 0.05 * 4. Model SPBP + gel + Derinat fifteen 5 33.3 0.45 ± 0.29 <0.05 * <0.01 ** Note: * - significance of differences compared with control
** - significance of differences compared with comparison series 2 and 3

table 2 CHANGES IN REGENERATIVE ACTIVITY OF MESOTHELIOCYTES IN ANIMALS BY 14 DAYS AFTER MODELING OF SPBP Series % mature cells % young cells KCI Volume ratio 1. Model (control) 87.8 12,2 0.186 0.390 2. Model SPBP + gel 87.3 12.7 0.187 0.391 3. Model SPBP + Derinat 85.3 14.7 0.197 0.396 4. Model SPBP + gel + Derinat 64 36 0.324 0.518

The data obtained during the experiments were processed using variational statistics methods to determine the uniformity of the distribution of the sample by the Kolmogorov criterion, and depending on the type of distribution, the significance of the differences was estimated either by Wilcoxon criteria and using one-way analysis of variance, or using the Mann-Whitney criterion. The calculation of average values (arithmetic mean, mode, median, average error of the mean), determination of the reliability of their differences - p (considered significant if this indicator was less than or equal to 0.05). Standard correlation analysis was also used.

In the control series, adhesions occurred in all animals, the severity of adhesions by the method of semantic differential was 1.87 ± 0.16 points. In the second series, adhesion was not revealed in 4 animals; its severity by the method of semantic differential was 0.65 ± 0.19 points. In the third series, adhesions were determined in all animals; the severity of SPBP was 1.54 ± 0.17 points. In the fourth series, adhesion was not observed in 10 animals; its severity was 0.45 ± 0.29 points.

In a histological examination in animals with SPBP, the morphological organization of adhesions corresponded to the term for removing the animal from the experiment. The basis of the tissue was maturing collagen fibers with a tendency to orientation. The cell composition was poor, represented by fibroblasts, fibrocytes, single cells of the leukocyte series. The phenomena of neoangiogenesis were noted.

In a cytological examination of smears, the ratio of mature and young mesotheliocytes was studied. The prevalence of young forms was noted in the fourth series. We also determined the karyocytoplasmic index (the ratio of the characteristics (size and volume) of the nucleus to the characteristics of the cytoplasm). Maximum results were obtained in the fourth series. Based on the results obtained, the following conclusions are made:

- when the gel is introduced with Derinat deposited in the abdominal cavity, the severity of the adhesive process significantly decreases by 3 times compared with the control series and the Derinat series and 2.2 times compared with the introduction of the gel only;

- regenerative activity is most pronounced in the fourth series - the introduction of a gel with Derinatum deposited in it (an increase in the proportion of young mesotheliocytes in fingerprints by 3 times, an increase in the karyocytoplasmic index by 43% (in diameter) and 25% (in volume)).

Thus, when a gel is introduced into the abdominal cavity with an immunomodulator deposited in it, the likelihood of the formation of intra-abdominal adhesions is reduced in animals, and the severity of postoperative SPP is also reduced. This is explained by the fact that the gel has a “barrier” property and is able, by means of hydroflotation of deserted surfaces, to prevent their consolidation, gluing fibrin deposited from the peritoneal effusion and the formation of connective tissue adhesions, and the immunomodulator activates the processes of cellular and humoral immunity, increases resistance to infections, has high reparative and regenerative properties.

Claims (1)

A method for preventing the formation of postoperative adhesions, characterized in that during surgery on the organs of the serous cavities, the deserted and / or inflamed parts of the organs and the walls of the cavity are covered with a sterile Lintex-Mesogel gel pre-mixed with Derinat, and the volume of Derinat is from 1 to 25% of the total volume of the mixture.