RU2349329C1 - Method of anastomosis inefficiency prevention for hollow gastroenteric tract organs of morbid adiposity and metabolic syndrome patients, using enterosan medicine - Google Patents

Abstract

FIELD: medicine.

SUBSTANCE: invention concerns medicine, particularly abdominal surgery and prevention of anastomosis inefficiency of hollow gastroenteric tract organs of morbid adiposity and metabolic syndrome patients. Method involves Enterosan (E) administration by 2 capsules 3 times per day for two weeks before operation. Then 30-50 ml of E is administered to stomach on the 2^nd day after operation in suspension form every 6 hours. Further E is administrated perorally: by 3 capsules 4 times per day on 3^rd to 7^th days, by 2 capsules 4 times per day on 8^th to 12^th day, further by 1 capsule 2 times per day for 7-10 days.

EFFECT: reduced inflammatory alterations, accelerated regeneration process in anastomosis area, normalisation of gastroenteric tract function.

5 dwg, 1 ex

Description

The present invention relates to medicine, in particular to abdominal surgery, and can be used for the treatment and prevention of insolvency of anastomoses of the hollow organs of the gastrointestinal tract.

Known methods for the prevention of insolvency of anastomoses using fibrin glue such as "Tissucol", glue "Sulfacrylate", "Tachocomb" (V.V. Plechev, V.M. Timerbulatov, R.Z. Latypov. - Diseases of the peritoneum. - Ufa. - 1999 - 1999 g.). However, for the Tissucol fibrin glue, additional conditions are necessary for dissolving and mixing the starting components at a strictly defined temperature and mode; carrier substances such as sponges and collagen fibers are often necessary to enhance the result. Moreover, this method of prevention does not have antibacterial activity, and can not always ensure the integrity of the anastomosis. "Tachocomb" also does not provide sufficient tightness of the intestinal suture; in spite of its hemostatic properties, it can cause the formation of hematomas (with continued bleeding, a hematoma forms under the Tachocomb film); does not have antibacterial activity. In addition, Tahokomb has a rather high cost, which is unfavorable financially. Sulfacrylate glue gives good results only in combination with allaplant and / or oxymethyluracil repair stimulants used locally on the anastomotic area, as well as with a prolonged action antibacterial suture material. The adhesive film polymerizes quickly, which creates certain difficulties in the formation of anastomoses.

The use of the above methods of prevention is ineffective in conditions of a “compromised” intestinal wall, that is, with peritonitis, intestinal obstruction, and creates additional technical difficulties for surgeons during the operation. Edema and microcirculation disorders in the anastomosis area are pronounced and persist for a long time, causing an additional risk of anastomotic failure. None of the above methods affects impaired metabolic processes in the body as a whole, which lead to insufficiency of immunobiological mechanisms and delayed defective regeneration.

The prototype of the invention is a method for the prevention of insolvency of hollow organs anastomoses in gastrointestinal surgery, which consists in the fact that, against the background of standard mechanical preparation, 5-oxymethyluracil is administered orally at a dose of 50 mg / kg twice a day for five days before surgery (application RU 2005141842 with priority of 12/27/2005).

In 1999, Enterosan was approved for use as a treatment for acute and chronic diseases of the gastrointestinal tract. (Order of the Ministry of Health of the Russian Federation No. 233 of June 11, 1999 / Registration Certificate No. 99/233/3. VFS No. 42-3412-99 approved June 11, 1999).

Using glycosaminoglycans (acid mucopolysaccharides, chondroitin sulfate), which are part of the drug, Enterosan activates the course of redox processes associated with intracellular, parietal, intracavitary digestion; adsorbs pathogenic microorganisms and their toxins, salts of heavy metals, normalizes the intestinal microflora (reduces the processes of fermentation and decay, acts bacteriostatically on gram-positive microorganisms). Sialomucins, as constituents, have an enteroprotective effect, restore the preepithelial barrier, and protect against the effects of damaging factors (xenobiotics, radionuclides, toxic chemical compounds, etc.).

Previously studied the complex effect of Enterosan on the gastrointestinal tract. The drug was prescribed for celiac disease, acute and chronic gastritis, enteritis, colitis, maldegistia syndrome, malabsorption, chronic pancreatitis with impaired digestion, dysbiosis, irritable bowel syndrome, short bowel syndrome, biliary sludge, atopic bronchial asthma and other diseases. The effect of Enterosan during surgical interventions on the organs of the gastrointestinal tract has not been studied.

EFFECT: reduction of inflammatory changes and acceleration of regeneration processes in the anastomosis zone, normalization of the gastrointestinal tract.

The specified technical result is achieved by the fact that in the method for the prevention of insolvency of anastomoses of the hollow organs of the gastrointestinal tract, including the administration of a drug in the preoperative period, Enterosan is administered as a drug for 2 weeks before surgery, 2 capsules 3 times a day, it is additionally administered in the postoperative period, namely: on day 2, the drug is injected into the stomach in the form of a suspension in a volume of 30-50 ml every 6 hours; from 3 to 7 days - 3 capsules orally 4 times a day; from 8 to 12 days - orally, 2 capsules 4 times a day; then for 7-10 days, 1 capsule 2 times a day.

The proposed method is illustrated by the following drawings: figure 1 shows the dynamics of the content of GAG (μm / g of tissue) in the intestinal tissue after modeling a single-row anastomosis "end-to-end" in the area of the duodenum; figure 2 - the dynamics of the protein content in the intestinal tissue after modeling a single-row anastomosis "end-to-end" in the area of the duodenum; figure 3 - the dynamics of the RNA content in the intestinal tissue after modeling of the end-to-end anastomosis in the area of the duodenum; figure 4 - epithelialization of the anastomotic region. Creeping of the epithelium on the formed granulation tissue. Necrotic changes were not detected. 15 days. The treated group. X 120. Coloring Van Gieson; figure 5. - inflammatory-necrotic changes in the intestinal wall in the area of the anastomosis with the phenomena of epithelialization of the defect along the edge. 15 days. Untreated group. X 120. Coloring Van Gieson.

The proposed method is as follows. Within 2 weeks before the planned operation, Enterosan is prescribed 2 capsules 3 times a day 20-30 minutes before meals. Starting from 2 days after surgery, Enterosan is administered according to the following scheme:

On the 2nd day after surgery, the drug is administered through a nasogastric tube into the stomach in the form of a suspension (the contents of 2 capsules are stirred in 30-50 ml of saline solution) every 6 hours;

from 3 to 7 days after surgery - orally, 3 capsules 4 times a day 20-30 minutes before meals, with a small amount of water;

from 8 to 12 days after surgery - orally, 2 capsules 4 times a day for 20-30 minutes before meals, with a small amount of water;

then for 7-10 days, 1 capsule 2 times a day.

We conducted studies to study the results of the formation of anastomoses of the hollow organs of the gastrointestinal tract when using Enterosan.

It is known that inflammatory processes that develop in a wound cause an increase in the content of protein and glycosaminoglycans (GAG) and a decrease in the content of RNA.

Experimental studies were performed on 90 white Wistar rats of the Ruttus norvegicus breed at the age of 3-4 months. Animals in the amount of 74 animals were divided into 4 groups: group 1 - intact (6 animals); Group 2 - operated, untreated, which were injected with distilled water in an equivalent volume (32 heads), group 3 - operated, treated, which were injected with Enterosan solution 3 times a day for 20 days (32 heads, the daily dose was calculated according to the weight of the animals), Group 4 - operational background - operated animals that were slaughtered 5 hours after surgery (4 heads).

Under anesthesia in animals, single-row end-to-end anastomoses were applied in the area of the duodenum. In total, 90 animals were operated on, 16 of them died on 1-3 days after operations. For histological examination, 6 additionally operated animals from groups 2 and 3 were taken within 3, 7, 15 days after surgery.

All manipulations with animals were carried out in accordance with the "Rules for the use of experimental animals" (Order of the Ministry of Health of the USSR No. 755 of 08/12/1977).

At autopsy, the presence of a blood clot was observed in the area of the operation in all operated animals from day 1-3. In animals treated with Enterosan, its size was smaller. From the second to the fifth day, intestinal hyperemia was observed at the site of the operation, spreading to nearby sections of the intestine. More pronounced hyperemia was observed in untreated animals.

From 5-10 days in all rats not receiving Enterosan, purulent exudate was observed, which was present both inside the lumen of the intestine and in the abdominal cavity. This state of the intestine in the group treated with Enterosan was observed in only one animal on day 7.

From day 7, untreated animals observed multiple adhesions; in some cases, fusion of the stomach, liver, peritoneum, and operated site was observed.

From 10 days, in rats treated with Enterosan, the intestinal condition returned to normal - the intestinal color corresponded to the intestinal color of intact animals.

On day 20 in the group of animals treated with Enterosan, the anastomosis line was not visually or palpated determined. In the untreated group, the formation of a gross disfiguring cone-shaped scar was observed.

In the treated group, GAG normalization of 9.06-8.53 μM / 1 g of tissue occurred on days 7-10, which indicates an intensive biosynthesis of collagen in granulation-fibrous tissue and is associated with the process of intensive tissue regeneration. In the control group, a high GAG level of 10.8-14.67 μM / 1 g of tissue remained during the experiment.

In the control group, on the 15th day there was a sharp increase in the level of GAG (14.68 μM / 1 g of tissue), in our opinion this was due to a violation of the repair process at the stage of scar organization (Fig. 1).

The maximum increase in protein concentration in the tissue in the treated group occurred on the 2nd day - 252.39 mg / g and remained at a high level up to 10 days, which may indicate the activity of the reparative processes taking place in this tissue. Normalization of protein concentration occurred on day 15 (75.55 mg / g). In the control group, the minimum protein concentration was also reached on day 15, but amounted to 107.79 mg / g with no downward trend (Fig. 2).

The RNA level in the treated animals returned to normal on the 5-7th day and amounted to 9.5-10.1 μg / mg, while in the control group on the 20th day only the RNA level rose to 8.88 μg / mg (Fig. 3) .

According to the histological examination on day 3, significant histological differences in the compared groups were not detected. At a later date, on day 7, in rats treated with Enterosan, the initial regeneration of the mucous membrane with the “creep” of the ulcer edge epithelium onto the cell detritus along the granulation tissue is visible on the preparations, while in untreated animals in the anastomotic region there is only a slight decrease in necrotic changes against the background of continuing to form granulation tissue. On the 15th day in the group of animals treated with Enterosan, epithelization of the anastomotic region was observed: epithelium crawled onto the formed granulation tissue, necrotic changes were not detected (figure 4). In contrast to the group of untreated animals, where the repair process proceeded more slowly, with inflammatory-necrotic changes in the intestinal wall in the area of the anastomosis with the phenomena of epithelialization of the defect along the edge (Fig. 5).

Enterosan has a high activity as a stimulator of reparative regeneration. The use of Enterosan reduces inflammatory changes and causes an acceleration of regeneration processes in the anastomotic zone, normalizes the functioning of the gastrointestinal tract, stimulates the secretion of bile, improves the detoxification function of the liver, which is of great importance in the surgical treatment of patients with morbid obesity and associated metabolic disorders.

The use of Enterosan in the pre- and postoperative period can be recommended as one of the ways to prevent anastomotic failure in surgery of the gastrointestinal tract.

After conducting experimental studies, this method for the prevention of anastomotic insolvency was tested in a surgical hospital. We performed the following planned operations on the hollow organs of the gastrointestinal tract: gastric resection for peptic ulcer, resection of the small intestine with the application of side-by-side or end-to-end anastomoses, vertical gastroplasty with morbid obesity.

Clinical example. Patient M., 40 years old (source # 36677/06), was admitted to the hospital with complaints of overweight (124 kg with a height of 169 cm), hypertension BP 180 \ 90 mm Hg) decreased working capacity . According to fibroesophagoscopy with pH - metry - cardia insufficiency, erosive reflux - esophagitis, hyperacid state of pH up to 2.1, gastroesophageal reflux. Esophagomanometry: the gradient of the esophageal-gastric transition is reduced to 50 mm water column Conservative therapy is unsuccessful. The patient before the operation received Enterosan 2 capsules 3 times a day for 20-30 minutes before meals for 2 weeks. Consulted by a physician, cardiologist and endocrinologist, and then operated on. Performed vertical gastroplasty, with the imposition and dissection of two-row stitching seams with the creation of a fundoplication cuff.

In the postoperative period, the patient received Enterosan, starting from 2 days after surgery according to the following scheme:

2 days - the drug was administered through a nasogastric tube in the form of a suspension (the contents of 2 capsules were stirred in 30-50 ml of saline solution) every 6 hours;

from 3 to 7 days orally, 3 capsules 4 times a day 20-30 minutes before meals, with a small amount of water;

from 8 to 12 days orally, 2 capsules 4 times a day 20-30 minutes before meals, with a small amount of water;

then for 7-10 days, 1 capsule 2 times a day.

The postoperative period was uneventful, without complications, insolvency of the anastomosis was not noted. In the long-term period, after 6 months, a positive picture of the course was observed.

Claims (1)

A method for the prevention of insolvency of anastomoses of the hollow organs of the gastrointestinal tract, comprising administering the drug in the preoperative period, characterized in that Enterosan is administered as a drug for 2 weeks before surgery, 2 capsules 3 times a day, it is additionally administered in the postoperative period, namely: on day 2, the drug is injected into the stomach every 6 hours in the form of a suspension, which is obtained by mixing the contents of two capsules in 30-50 ml of physiological saline; from 3 to 7 days - orally, 3 capsules 4 times a day; from 8 to 12 days - orally, 2 capsules 4 times a day; then for 7-10 days, 1 capsule 2 times a day.

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