RU2851243C1 - Method of endomesenteric lymphotropic therapy in treatment of widespread peritonitis in postoperative period - Google Patents

Abstract

FIELD: medicine.

SUBSTANCE: invention relates to surgery and oncology and can be used for endomesenteric lymphotropic therapy in the treatment of widespread peritonitis in the postoperative period. The method involves the installation of endomesenteric drainage and the use of medications. Endomesenteric drainage contains an anti-reflux valve and polyvinyl chloride catheters at a distance of 2 cm from the mesenteric edge of the intestine. The first is installed in the mesentery of the right colon. The second is installed in the mesentery of the transverse colon. The third catheter is placed in the mesentery of the left colon. Lymphotropic therapy is performed through endomesenteric drainage, during which 16 IU or 32 IU of lidase diluted in 2 ml of 0.025% novocaine is administered. Heparin is administered in an amount of 0.1-10 IU/ml, and Derinat is administered in a volume of 5 ml every other day for 10 days. After 10 minutes, Ceftriaxone is administered in an amount of 2 g per day.

EFFECT: increased effectiveness of treatment of patients with acute surgical pathology and reduced hospitalisation time due to the administration of drugs to the pathological focus of the entire large intestine and adequate lymphotropic therapy with a reduction in the number of exudative-inflammatory complications.

1 cl, 2 dwg, 1 ex

Description

Field of technology to which the invention relates

The invention relates to the field of medicine, to surgery, in particular in oncology, and can be used in endomesenteric lymphotropic therapy for acute abdominal surgical pathology in the postoperative period.

State of the art

A method is known for treating acute inflammatory diseases of the abdominal organs by draining lymph, cleansing it of toxins, and then reinfusing it. In order to create a depot of drugs and ensure a high therapeutic concentration, drugs are introduced into the central lymphatic duct retrogradely, holding them for 8 hours by clamping the drainage and repeating the procedure every 8 hours for 3-5 days (see A.S. No. 703092, IPC A61B 17/00, published 12/15/1979).

The disadvantages of this method are: - lymphovascular and intranodular catheterization is associated with surgical trauma, - to perform it, the doctor must be proficient in microsurgical techniques, as well as have special equipment, - during endolymphatic therapy, damage to the lymphatic vessel is possible, as a result of which it is necessary to repeat the operation to install the catheter, - the final formation of the lymphatic system occurs by the age of 12, which makes the advisability of using this method in children questionable.

A method for treating widespread peritonitis is known, which includes intraportal reinfusion of oxygenated blood, while the patients undergo a surgical operation, during which the source of peritonitis is eliminated, nasointestinal intubation and lavage of the entire small intestine are performed, followed by intraintestinal administration of 16 g of enterosorbent and the antibiotic ampicillin at a dose of 1.0 g, replacement of the intubation tube with a thin two-channel tube, catheterization of the umbilical vein and insertion of drainage tubes into the abdominal cavity, and in the postoperative period, against the background of external decompression of the stomach, 400 ml of oxygen-containing saline solution is administered intraintestinally through a tube 2 times a day at a rate of 20 drops per 1 min and 15 g of enterosorbent in 150 ml of saline solution 3 times a day, and also once a day intraportal reinfusion of autologous blood taken from peripheral vein at the rate of 2 ml/kg and oxygenated for 1 hour by reinfusion in an oxygenator at a gaseous oxygen flow rate of 10 l per 1 min, and also intraportally 3 times a day, 100 ml of metrogil is administered at a rate of 40 drops per 1 min, the treatment is carried out for 5-6 days after the operation and is stopped when the patient's condition improves, intestinal peristalsis is restored and a negative result is obtained from a bacteriological examination of blood from the portal vein for the presence of anaerobic microflora (see patent RU No. 2154997, IPC A61B 17/00, A61M 1/00, A61M 1/14, A61K 31/415; Published on August 27, 2000, Bulletin No. 24).

The disadvantage of this method is the labor-intensive nature of using oxygenated autologous blood, as well as a decrease in the patient's quality of life in the early postoperative period due to the installation of nasointestinal drainage.

A method for treating widespread purulent peritonitis is known, which includes sanitizing the abdominal cavity with antiseptic solutions, active sorption drainage of the abdominal cavity by placing containers with a temosorbent into it, and lymphotropic therapy during surgery - laparostomy, while sorption drainage of the abdominal cavity is carried out with a carbon hemosorbent VNIITU-1 by placing 6-8 nylon containers into it, and lymphotropic therapy is carried out by introducing 80-100 ml of 0.25% novocaine solution, 16 U of lidase, 0.5 g of selemicin, 2.5 thousand U of heparin into the root of the mesentery of the small intestine, then the laparotomy wound is left open, and lymphotropic therapy is carried out with subsequent dressings (see patent RU No. 2306927, IPC A61K 31/245, A61K 31/727, A61K 38/47, A61K 7036, A61P 41/00, A61B 17/00, published 09.27.2007, bulletin No. 27).

The disadvantage of this method is the management of an open laparotomy wound, as well as the fact that novocaine at a concentration of 0.25% inhibits the pumping function of the lymphangion up to its complete suppression, which contradicts the implementation of lymphotropic therapy.

A method for treating the obstructive form of acute adhesive small intestinal obstruction is known, wherein the following parameters are determined in the patient: duration of the period from the onset of the disease to admission to the hospital, number of operations on the abdominal organs in the anamnesis, intensity and nature of abdominal pain, level of obstruction, diameter of the small intestine, body temperature, pulse, potassium content in the blood serum; each of the specified parameters is expressed in points, assessing them as follows: duration of the period from the onset of the disease to admission to the hospital less than 36 hours - "1" point, from 36 to 72 hours - "-2" points and over 72 hours - "-5" points; no operations on the abdominal organs in the anamnesis - "-5" points, presence of one such operation - "-1" point, presence of two or more such operations on the abdominal organs in the anamnesis - "1" point; moderate abdominal pain - "1" point, intense abdominal pain - "-5" points; Cramping abdominal pain - "1" point, constant abdominal pain - "-4" points, high or moderate obstruction - "3" points, low obstruction - "-1" point; small intestine diameter less than 40 mm - "3" points, equal to or more than 40 mm - "-3" points; body temperature less than 37°C - "1" point, equal to or higher than 37°C - "-3" points; pulse less than 85 beats per minute - "1" point, equal to or higher than 85 beats per minute - "-3" points; serum potassium content from 3.5 to 5.0 mmol/l - "-3" points, over 5.0 mmol/l - "-4" points, less than 3.5 mmol/l - "2" points; after which the points of all the assessed indicators are summed up and if the sum of points is less than "-8", emergency surgical intervention is performed; if the sum of points is more than "10", conservative therapy is carried out, including correction of metabolic disorders, decompression of the lower gastrointestinal tract; and if the sum of points is from "-8" to "10", conservative therapy is carried out, including correction of metabolic disorders, decompression of the lower gastrointestinal tract, supplemented by endoscopic nasointestinal decompression and, if the therapy is ineffective within 12 hours, surgical intervention is performed (see patent RU No. 2455943, IPC A61B 17/00, A61B 17/32, A61B 5/00, A61B 5/01, A61B 1/273, publ. July 20, 2012, bulletin. No. 20).

The disadvantage of this method is the difficulty of choosing between conservative and surgical treatment methods in the required volume.

A method is known for treating purulent-septic complications in acute destructive pancreatitis by introducing a gaseous ozone-oxygen mixture with an ozone concentration of 10 mg/l or less, wherein the ozone-oxygen mixture is introduced from both sides of the retroperitoneal space into the paranephric tissue in a volume of up to 500 ml inclusive on each side, the course of treatment is 5-10 sessions, every 1-3 days (see patent 2455943, IPC A61M 25/01, A61B 17/00, A61K 33/00, A61P 41/00, published 20.07.2012, bulletin No. 20).

The disadvantage of this method is its lack of effectiveness.

A method of lymphotropic administration of drugs in the treatment of diseases of the abdominal organs is known, including the administration of drugs through a catheter installed according to Seldinger, while in the patient's sitting position, straightened, the spinous process of the twelfth thoracic vertebra is determined, stepping back to the left from the spinous process by 2.5-3.0 cm, anesthesia of the skin and underlying tissues is performed with a local anesthetic with a conventional injection needle, then with a Tuohy needle, moving along the upper edge of the rib to the midline of the body, they reach the transverse process of the twelfth thoracic vertebra, go around it laterally and from above, advance the needle into the retroperitoneal space to the site of formation of the thoracic lymphatic duct and perform through the installed catheter the introduction of Lidase 32 U, diluted in 2 ml of 0.25% novocaine, then after 5-10 minutes 1000 mg of cephalosporin third or fourth generation, diluted in 5 ml of 0.25% novocaine, 2 times a day for 5 days; Derinat solution 5 ml once every two days for 10 days, 2% novocaine solution in the amount of 20 ml every 8 hours 3 times a day (see patent RU No. 2561832, IPC A61M 25/01, A61K 38/47, A61K 31/245, A61K 31/546, A61K 31/711, A61P 1/18, published 10.09.2015, bulletin No. 25).

The disadvantage of this method is the introduction of drugs into the retroperitoneal space to the site of formation of the thoracic lymphatic duct, which is associated with a high risk of surgical injury to the lymphovascular and intranodular structures, as well as the fact that it can be accompanied by damage to the lymphatic vessel during lymphotropic therapy. In addition, novocaine at a concentration of 0.25% inhibits the pumping function of the lymphangion up to its complete suppression.

A method is known for treating purulent-septic complications in acute destructive pancreatitis by introducing a gaseous ozone-oxygen mixture with an ozone concentration of 10 mg/l or less, wherein the ozone-oxygen mixture is introduced from both sides of the retroperitoneal space into the paranephric tissue in a volume of up to 500 ml inclusive on each side, the course of treatment is 5-10 sessions, every 1-3 days (see patent RU 2541269, IPC A61M 25/01, A61B 17/00, A61K 33/00, A61P 41/00, published 10.02.2015, bulletin No. 4).

The disadvantage is the lack of efficiency of the method.

The closest in technical essence and the achieved positive effect and accepted by the authors as a prototype is the method of performing endomesenteric lymphotropic therapy, which consists in the fact that after the completion of the main stage of the operation, intraoperatively, an invented polyvinyl chloride special catheter for lymphotropic therapy in the postoperative period is endomesenterically installed into the intestinal mesentery and secured with thin catgut in the intestinal mesentery, the outer end of the catheter is brought out of the abdominal cavity through a counter-opening and fixed to the skin of the anterior abdominal wall with a silk thread, while the catheter is installed at a distance of 2 cm from the mesenteric edge of the intestine, in the postoperative period, through a catheter installed in the intestinal mesentery, lymphotropic therapy is carried out using a glucose-novocaine mixture in a ratio of 1: 1 at a dose of 4 ml per kg of body weight of the patient with lidase (0.5 units/kg), or add heparin (80 units/kg) taking into account the patient's blood clotting, thymogen at a dose of 150 mcg, broad-spectrum antibiotics, for example, III-IV generation cephalosporins: cefazolin or ceftriaxone, in a single therapeutic dose, subsequently taking into account the sensitivity of the abdominal microflora to them (see Egamov Yu.S., Ruziev A.E., Khaidarov S.A., Endomesenteric lymphotropic therapy for abdominal surgical pathology in the postoperative period. Moscow surgical journal, 2022. No. 1. P.69-74 https://doi.org/10.17238/2072-3180-2022-1-69-74).

The disadvantage of this method is the local installation of a catheter in one part of the mesentery of the colon, the intestine, which is inappropriate if the inflammatory process involves the entire mesentery of the colon, in diffuse peritonitis, also the drugs and their dosages used in the above lymphotropic therapy are indicated in therapeutic dosages and have not been proven from a scientific point of view, namely, their effect on the contractile function of the lymphangion, and also the fact that the antibacterial drug cefazolin belongs to the first generation cephalosporins, and not III-IV.

Disclosure of invention

The objective of the proposed invention is to develop a method for endomesenteric lymphotropic therapy for acute abdominal surgical pathologies in the postoperative period, which reduces the risk of postoperative complications, reduces the duration of hospitalization and improves the patient's quality of life.

The technical result that can be obtained with the help of the proposed invention is reduced to the development and application of a method of endomesenteric lymphotropic therapy for acute abdominal surgical pathology in the postoperative period, with the help of which it is possible to increase the effectiveness of treatment of patients with acute surgical pathology and reduce the duration of hospitalization by introducing medicinal substances to the pathological focus of the entire large intestine and conducting adequate lymphotropic therapy with a decrease in the number of exudative-inflammatory complications.

The technical result is achieved using the method of endomesenteric lymphotropic therapy in acute abdominal surgical pathology in the postoperative period, including the installation of endomesenteric drainage for performing lymphotropic therapy after the main stage of the operation and the use of drugs, wherein the endomesenteric drainage contains three special polyvinyl chloride catheters installed in different parts of the mesentery of the large intestine, and an antireflux valve for unidirectional movement of drugs used for lymphotropic therapy, and for lymphotropic therapy the following scheme is used as lymphostimulators: administration of Lidase 16 U or 32 U, diluted in 2 ml of 0.025% novocaine; heparin 0.1-10 U/ml taking into account the patient's blood clotting; Derinat solution 5 ml every other day for 10 days; then, after 10 minutes, administration of broad-spectrum antibiotics - third-generation cephalosporins, ceftriaxone 2 g per day, subsequently taking into account the sensitivity of the abdominal microflora to them.

Brief description of drawings and other materials

Fig. 1 shows a method of endomesenteric lymphotropic therapy for acute abdominal surgical pathology in the postoperative period, implementation of the method.

Fig. 2 also shows a diagram of endomesenteric drainage.

Implementation of the invention

Currently, lymphatic therapy is divided according to its mechanism of action as follows:

- correction of microcirculation: a) stimulation of lymph formation and lymph drainage; b) inhibition of lymph formation and lymph drainage;

- antibacterial therapy;

- immunomodulatory therapy;

- antitumor therapy;

- detoxification therapy;

- combination therapy.

It has been established that regional lymphotropic administration of drugs significantly exceeds their concentration in the target organ compared to traditional administration methods. Thus, antibiotic concentrations in the liver, pancreas, and gastric wall are 1.6-4.2 times higher after lymphotropic administration than after intramuscular administration. The concentration of 5-fluorouracil in the greater omentum and pancreas after regional lymphotropic administration is 3-4 times higher than after intravenous administration. Intravenous and intramuscular administration of antibiotics creates a short-term toxic concentration of the drug in the blood within 30-60 minutes, which activates the body's natural antibiotic elimination systems: the liver and kidneys. Given the lack of lymphatic replenishment, the drug concentration in the blood, and therefore in organs and tissues, progressively decreases. As a result, the half-life of common antibiotics is short: 0.5-1 hour for cefazolin and 2 hours for cefotaxime. Numerous studies have shown that when administered via the lymphatic system, antibiotics remain in the lymphatic system for up to 24-48 hours, followed by gradual release into the bloodstream via the thoracic duct.

Lymphatic drug administration allows antibiotics to be administered once daily, significantly reducing the daily dose. This helps reduce the drug's toxic effects on the body, its allergenicity, and also lowers the cost of treatment. The advantages of lymphatic drug administration methods over traditional ones include faster recovery and rehabilitation, shorter hospital stays, fewer complications, and fewer side effects.

Lymph flow from the cecum and appendix occurs through the ileocolic, prececal, and postcecal lymph nodes. Lymph flow from the ascending colon, transverse colon, and descending colon occurs through the mesenteric, paracolic, right, middle, and left colic lymph nodes. Lymph from the sigmoid colon drains into the inferior mesenteric (sigmoid) lymph nodes. Lymph from the rectum drains into the internal iliac (sacral), subaortic, and superior rectal lymph nodes.

Therapeutic and preventive effects on the lymphatic system should be aimed at normalizing all of its components, restoring the drainage functions of the lymphatic capillaries and vessels, stimulating the detoxification and effector functions of lymphoid cells and lymphoid organs, and optimizing the state of the connective tissue system with its cellular and extracellular components.

The contractile activity of smooth muscle cells called lymphangions is currently recognized as the primary driving force behind lymph flow through the lymphatic system. A lymphangion is a section of a lymphatic vessel between two valves. It consists of the vessel wall and two valves—distal and proximal.

In endolymphatic therapy, medicinal substances are diluted with various solvents: novocaine, isotonic sodium chloride solution, and distilled water. Local anesthetics, including novocaine, are known to stimulate spontaneous contractility of vascular smooth muscle cells and increase their basal tone at low concentrations. At higher concentrations, the vasoconstrictor effect decreases and vasodilation develops. The experiment used novocaine concentrations of 0.025%, 0.05%, 0.1%, and 0.25%. It was found that both flushing and perfusion with a 0.025% novocaine solution resulted in increases in systolic and cardiac output, with this effect being more pronounced with perfusion. Increasing the concentration of novocaine solution to 0.05% does not lead to reliable differences in the change in systolic and minute volumes, as well as the contraction frequency, either during irrigation or perfusion. With an increase in the concentration of novocaine solution to 0.1%, the systolic volume during perfusion decreases almost 2-fold compared to the change in systolic volume during irrigation with the same solution: 43.5±6.88% and 80.4±5.11% of the initial value, respectively. The minute volume during perfusion with 0.1% novocaine solution is maintained due to an increase in contraction frequency (154.2±13.56%). Perfusion with 0.25% novocaine solution in all cases, 10 experiments, led to complete reversible inhibition of the contractile and pumping function of the lymphangions, whereas during washing, inhibition was observed only in 2 cases; in the remaining 8 experiments, the values of systolic and minute volumes, as well as the frequency of contractions, were (32.2±21.04%, 21.7±13.57%, and 70.7-11.8% of the original, respectively).

Based on the data obtained, it can be assumed that the effect of novocaine solution is more pronounced when administered intrathecally to the lymphangion. A 0.025% novocaine solution exerts a stimulating effect, while with higher concentrations (0.05% and 0.1%), the inhibitory effects of novocaine solution begin to predominate. At a concentration of 0.25%, this leads to "suppression" of the contractile and, consequently, pumping function of the lymphangion.

Perfusion with isotonic sodium chloride solution resulted in a decrease in systolic and minute volumes of 47.2±10.31% and 54.2±6.93% of the baseline, respectively, despite a slight increase in contraction frequency of 120.7±8.32%. Intravenous administration of distilled water to isolated lymphangion in all cases resulted in inhibition of the contractile and pumping functions of the lymphangion. It was established that all studied substances used as drug solvents had a predominantly inhibitory effect on vascular motility. However, isotonic sodium chloride solution inhibited the phasic contractile activity of lymphatic segments, as well as their transport function, to a lesser extent than novocaine solution (0.25%) and distilled water.

From the above, the following conclusions can be drawn: - a 0.025% novocaine solution stimulates the lymphangion's pumping function, while 0.25% novocaine inhibits the lymphangion's pumping function, even to the point of completely suppressing it; - an isotonic sodium chloride solution and distilled water inhibit the lymphangion's pumping function, while an isotonic sodium chloride solution inhibits the lymphangion's pumping function to a lesser extent than distilled water, the action of which leads to irreversible suppression of the lymphangion's pumping function.

Experimental studies of penicillin antibiotics, such as benzylpenicillin sodium, third-generation cephalosporins, such as claforan, and aminoglycosides, such as gentamicin sulfate, at concentrations most commonly used in clinical practice are conducted on isolated sections of bovine mesenteric lymphatic vessels containing a lymphangion with its valve and the proximal valve of the next lymphangion. Longitudinal and transverse displacement of the drug, as well as systolic ejection volume, are recorded. These data are used to determine the heart rate and cardiac output. Benzylpenicillin sodium is tested at two doses: 1 million and 2 million U. Eight perfusions were performed with the 1 million U dose. In this case, the systolic volume decreased to 46.6% of the initial value, and the contraction frequency increased to 126.2%, which maintained the minute volume at the level of 50.7%. With an increase in the dose to 2 million U, a decrease in systolic volume to 39.3% was observed, while the contraction frequency increased to 144.7%, and the minute volume decreased to 47.4% of the initial value. Claforan solution was studied at a concentration of 2.5 g / L and 5 g / L, 12 perfusions were performed. When perfused with Claforan solution at a concentration of 2.5 g / L, a decrease in systolic volume to 81.1% of the initial value, minute volume to 71.4% is noted, and a decrease in contraction frequency to 87.3% is also observed. With an increase in concentration to 5 g / L, a more pronounced decrease in systolic and minute volumes is revealed. Thus, the systolic volume significantly decreases to 51.6% of the initial value, the minute volume – to 48.1%, the heart rate does not change (96.5%). The effect of gentamicin sulfate was also studied in two concentrations: 8 and 16 g/L. With a concentration of 8 g/L, 5 perfusions were performed: in all cases, complete reversible inhibition of the contractile and pumping function of the lymphangion occurs within 2 minutes of antibiotic action. With an increase in concentration to 16 g/L, complete inhibition of the contractile activity of the lymphatic vessels is observed in all cases. Based on the experimental data obtained, it can be assumed that all the studied antibiotic solutions inhibit the contractile activity of the smooth muscle cells of the lymphatic vessels and reduce the systolic output of lymphangions, which leads to a decrease in lymph flow. However, the effect of these antibiotic solutions on the pumping function of lymphangions is not the same. Thus, Claforan solution inhibits lymphatic vessel contractility to a lesser extent than sodium benzylpenicillin. Perfusion with gentamicin sulfate solution, however, completely inhibits lymphangion function. This, in turn, suggests that the use of gentamicin sulfate solution leads to a rapid and prolonged artificial block in the vascular bed, thereby allowing for prolonged contact between the antibiotic and microorganisms at the site of inflammation.

From the above, we can conclude that antibiotics from the cephalosporin group (Claforan solution - a third-generation cephalosporin) can act on foci of inflammation that are distant from the injection site, since they slightly inhibit the transport function of the lymphatic vessels and do not lead to a complete block of the contractile activity of lymphangions.

Heparin (0.3-25 U/ml) in rat lymphangions causes dose-dependent biphasic changes in the parameters of contractile activity: low concentrations stimulate, medium and high concentrations inhibit. In the thoracic duct, the increase in frequency and amplitude is 153 and 129%, in the lymphangions of the intestinal trunk - 173 and 190%, respectively. Heparin (2.5-20 U/ml) in human lymphangions causes only inhibitory effects: a decrease in rhythm in 41.2% of lymphangions, a decrease in amplitude in 25%, a decrease in tone in 33% of lymphangions. Inhibitory effects deepen with increasing heparin concentration up to a complete cessation of contractile activity. Slow relaxation reaches 270-800 μN. After washout, the initial tone and the initial parameters of phasic rhythmic activity are quickly restored. In a series of experiments, ring segments of bovine mesenteric lymphatic vessels were perfused. Heparin (0.1-10 U/ml) stimulated contractile activity, which increased with increasing heparin dose. Higher heparin concentrations (15-50 U/ml) resulted in inhibitory effects, manifested by a decrease in contractile amplitude and a reduction in the rhythm of phasic spontaneous activity. Against the background of preliminary myocyte contraction (20 mM KCl), heparin at these concentrations caused a significant decrease in the level of tonic smooth muscle tension. A comparative analysis of data obtained on deendothelialized vessels and on vessels with intact endothelium showed that both groups had the same direction of changes in contractile activity, but different degrees of severity. In vessels with removed endothelium, the activating effect of heparin at low concentrations (0.1-10 U/ml) was more pronounced; conversely, the relaxation responses to high doses of heparin (15-50 U/ml) were more pronounced in vessels with preserved endothelium. Consequently, heparin, at both low and high concentrations, initiates the release of relaxing factor by the endothelium (Andreevskaya A.V., 1995).

From the above, we can conclude: the activating effect of lymphangiography is observed when using heparin in low concentrations of the drug (0.1-10 U/ml); on the contrary, relaxation responses are observed at high doses of heparin (15-50 U/ml).

The effects of lymphostimulating agents, such as thyrotropin-releasing hormone, lidase and terridecase, on the lymphangion pumping function were studied. It was found that perfusion with thyrotropin-releasing hormone (TRH) solution at concentrations of 1×10 ^'7 g/L and 1×10 e g/L resulted in a marked increase in systolic and minute volumes, as well as an increase in the contraction frequency. A thyrotropin-releasing hormone (TRH) solution concentration of 1×10 ^'7 g/L increased the minute volume by increasing the systolic ejection of lymphangion to 146.4*4.32% of the initial value, whereas perfusion with thyrotropin-releasing hormone (TRH) solution at a concentration of 1×10 e g/L maintained the minute volume at a high level of 144.3±11.63% of the initial value due to a sharp increase in the contraction frequency of lymphangion to 148.6±3.74% of the initial value.

A stimulating effect is observed when flushing lymphatic vessels with lidase solution at various concentrations. This effect is more pronounced with lidase solution concentrations of 16 U and 32 U, with a 1.5-fold increase in cardiac output. With lidase solution at a concentration of 64 U, cardiac output increases due to an increase in heart rate (130.4±4.84% of baseline), while systolic ejection increases slightly (118±9.5% of baseline).

Intralymphatic administration of terridecase solution also has a stimulating effect. However, the concentrations of this enzyme used have different effects on lymphangion pumping function. A terridecase solution concentration of 10 PE leads to a more pronounced increase in systolic and cardiac outputs (126±5.6% and 139±5.8% of baseline) compared to a 20 PE concentration, at which systolic volume remains unchanged or increases less significantly (109±4.61% of baseline).

Based on the experiments conducted, it can be assumed that all substances have a pronounced stimulating effect on the contractile and pumping functions of the lymphatic vessels. This effect depends on the concentrations used; a characteristic feature of all three preparations is their greater activity on the lymphatic vessels at the lowest concentrations used.

From the above, we can conclude that solutions of thyroliberin in concentrations of 1×10 ^'7 g/l and 1×10 e g/l; lidase in concentrations of 16 U and 32 U; terridecase in concentrations of 10 PE and 20 PE have a stimulating effect on the pumping function of the lymphangion.

The essence of the implementation of the method of endomesenteric lymphotropic therapy for acute abdominal surgical pathology in the postoperative period is as follows.

After completion of the main stage of the surgery, a polyvinyl chloride endomesenteric drainage tube 1 is inserted endomesenterically for lymphotropic therapy in the postoperative period. The endomesenteric drainage tube 1 contains three special catheters 2 and an antireflux valve 3 to ensure unidirectional flow of the medications used for lymphotropic therapy. Each catheter is a polyvinyl chloride tube with a blunt 25G needle at the end to reduce the risk of injury to adjacent structures. Each catheter 2 is inserted into a specific section of the mesentery of the colon: the first catheter is inserted into mesentery 4 of the right colon, the second into mesentery 5 of the transverse colon, and the third into mesentery 6 of the left colon. Each catheter 2 is inserted 2 cm from the mesenteric margin of the colon, not into the mesenteric root area. The choice of endomesenteric catheter location is based on maximal localization of the pericecal and prececal lymph nodes 7, as well as reducing the risk of damage to large blood vessels, the formation of a large hematoma in the mesentery, and ligation or compression of large lymphatic and blood vessels by injected medications. Each catheter 2 is secured in the mesentery with thin catgut. The outer end of the endomesenteric drainage tube is brought out of the abdominal cavity through the counter-incision and secured to the skin of the anterior abdominal wall with nylon suture 8.

In the postoperative period, lymphotropic medications are administered through endomesenteric drainage with an antireflux valve installed in various areas of the intestinal mesentery. The following regimen is used as lymphostimulants for lymphotropic therapy: administration of 16 U or 32 U of Lidase diluted in 2 ml of 0.025% novocaine; heparin 0.1-10 U/ml taking into account the patient's blood clotting; Derinat solution 5 ml once every other day for 10 days; then, after 10 minutes, broad-spectrum antibiotics are administered - third-generation cephalosporins: ceftriaxone 2 g per day.

In patients with peritonitis, the primary focus was on combating microbial factors. Analysis of the abdominal microflora in patients with peritonitis revealed the presence of E. coli, Staphylococcus aureus, and Pseudomonas aeruginosa in 84.5% of cases; in the remaining patients with acute peritonitis, cultures revealed a combination of microorganisms. The highest sensitivity of the abdominal microflora was found to cephalosporins: ceftriaxone and cefazolin (84.7% of patients with acute peritonitis). Considering the evidence base, Claforan solution is a third-generation cephalosporin that acts on inflammation foci distant from the injection site, slightly inhibits the transport function of lymphatic vessels and does not lead to a complete block of the contractile activity of lymphangions, unlike other groups of antibiotics and the greatest sensitivity of the microflora of the abdominal cavity in acute peritonitis, in the method of endomesenteric lymphotropic therapy for acute abdominal surgical pathology in the postoperative period, broad-spectrum antibiotics are used - third-generation cephalosporins, ceftriaxone 2 g per day, which are administered by drip.

Once antibiotic sensitivity is established, endomesenteric lymphotropic therapy is switched to the drug to which the bacteria were susceptible. Lymphotropic therapy for peritonitis is administered once or twice daily for 4-5 days, depending on the severity of the disease and the patient's condition.

An example of a specific implementation of the method of endomesenteric lymphotropic therapy for acute abdominal surgical pathology in the postoperative period.

Example. Patient M., 46 years old.

According to the patient, approximately three days ago, he began experiencing cramping abdominal pain, difficulty passing gas and stool. His condition worsened, and he did not immediately seek medical attention. He was hospitalized due to the worsening condition (sharply intensifying abdominal pain). The patient reported no underlying medical conditions.

Local status at the time of hospitalization: abdominal wall immobility, not involved in respiration. Palpation revealed the main symptom of peritonitis—protective tension of the anterior abdominal wall muscles—a "super-sign of all abdominal catastrophes," according to G. Mondor. Intestinal peristalsis was not audible. Abdominal tenderness was also detected upon palpation, particularly in the right iliac region. Symptoms of peritoneal irritation (Shchetkin-Blumberg and Razdolsky signs) were positive.

The following examinations were performed at the time of hospitalization:

Abdominal and chest X-rays reveal emphysema and diffuse pulmonary fibrosis in the basal portions of the root (few structures). Free gas is detected in the abdominal cavity, with horizontal levels in the small intestine. EED is 0.85+0.18 m3v.

Ultrasound examination revealed colonic evacuation dysfunction. Signs of a hollow organ in the left hypogastrium (sigmoiditis?), a small amount of fluid in the left hypogastrium. Thickening of the gallbladder walls, moderate presence of stagnant bile in it. Diffuse changes in the liver and pancreas. Calcifications in both kidneys.

General urine analysis:

Color - light yellow,

Transparency - transparent,

Specific gravity - 1020,

Protein - no,

The reaction is acidic,

Sugar - no,

Epithelium - 2-3 units per field of view,

Leukocytes - 1-2 in the field of view,

Red blood cells - no.

Blood biochemistry:

Total protein - 72 g/l,

Urea - 8.8 mmol/l,

Creatinine - 70 µmol/l,

Bilirubin - 5.9 mmol/l,

ALT - 44 IU/l,

AST - 38 IU/L,

Pancreatic amylase - 15 IU/l,

Na - 135 mmol/l, K - 4.2 mmol/l, Cl - 101 mmol/l.

Complete blood count:

Erythrocytes - 4.08×10 ¹² /l,

Leukocytes - 15.3×10 ⁹ /l,

Band neutrophils - 24%,

Segmented neutrophils - 60%,

Lymphocytes - 11%,

Monocytes - 3%,

ESR - 41 mm/h.

ECG: Sinus rhythm, horizontal EOS.

Examination by a general practitioner: chronic cholecystitis, remission. Calcifications in both kidneys.

Based on the objective status and data from additional examinations of the patient, a clinical diagnosis was established: acute appendicitis.

Surgery: Laparotomy, appendectomy, abdominal debridement and drainage. Placement of endomesenteric drainage.

Description of surgery: Midline laparotomy. A moderate amount of turbid exudate with an unpleasant foul odor was found in all sections of the abdominal cavity. The exudate was drained and taken for bacteriological examination of the microflora and determination of antibiotic sensitivity. During exploration of the small intestinal loops, the cecum and ascending colon were moderately distended. A ruptured abscess was discovered in the small pelvis, the walls of which were the pelvic peritoneum, bladder, cecum and sigmoid colon, mesentery, and loops of the small intestine. The abscess contained an 8-cm-long vermiform appendix, black in color near its apex. Fibrin deposits were present on the small intestinal loops and the mesentery in the area of the abscess. No other abdominal pathology was detected. The mesentery of the appendix was sutured, ligated, and transected. Appendectomy with purse-string and Z-shaped sutures inserted into the appendix stump. Abdominal lavage (5 liters of furacilin solution). Hemostasis and foreign body monitoring. Gauze swab (cigarette) placed into the abscess cavity through a counter-incision in the right iliac cavity.

After completing the main stage of the surgery, a special polyvinyl chloride drainage system consisting of three catheters and an antireflux valve was inserted endomesenterically. Each catheter was inserted into a specific section of the mesocolon: the first catheter into the mesocolon of the right colon, the second into the mesocolon of the transverse colon, and the third into the mesocolon of the left colon. Each catheter was secured 2 cm from the mesocolon's mesenteric margin using thin catgut in the mesocolon. The outer end of the endomesenteric drainage system was brought out of the abdominal cavity through a counter-incision and secured to the skin of the anterior abdominal wall with nylon suture.

Drainage tubes were placed in the pelvis, along the left lateral canal, and into the subhepatic space. The wound was sutured layer by layer down to the packing and tube. An aseptic dressing was applied.

Removed specimen: vermiform appendix, 8 cm long, black in color in the apex area.

Histological report: macroscopic description: an enlarged (8.5 x 2.5 x 2.0 cm), greenish-black appendix with a flabby wall and a foul odor. Microscopic description: necrosis in the appendix wall, layers are not differentiated, involving all walls of the appendix. Severe circulatory disorders, a significant proportion of the hemorrhagic component in the inflammatory infiltrate (Fig. 3). Conclusion: gangrenous appendicitis.

After the operation the following diagnosis was established:

Primary: acute gangrenous appendicitis, periappendiceal abscess that has ruptured into the abdominal cavity. Postoperative status: laparotomy, appendectomy, abdominal debridement and drainage, and placement of endomesenteric drainage.

Complication: widespread fibrinous-purulent peritonitis.

Concomitant pathology: chronic cholecystitis, remission. Calcifications in both kidneys.

In the postoperative period, lymphotropic administration of drugs was performed through endomesenteric drainage with an antireflux valve installed in various parts of the intestinal mesentery.

For lymphotropic therapy, the following regimen was used as lymphostimulants: administration of Lidase (32 U) diluted in 2 ml of 0.025% novocaine; heparin (10 U/ml) taking into account the patient's blood clotting; Derinat solution 5 ml every other day for 10 days; then, after 10 minutes, broad-spectrum antibiotics were administered - third-generation cephalosporins: ceftriaxone 2 g per day.

On the 2nd day of the postoperative period, the patient's intestinal peristalsis resumed, and on the 3rd day, spontaneous gas passage was noted.

On the third postoperative day, the bacteriological results showed Staphylococcus aureus, positive for ceftriaxone sensitivity. Antibacterial therapy was continued as before.

General urine analysis (3 days after surgery):

Color - light yellow,

Transparency - transparent,

Specific gravity - 1020,

Protein - no,

The reaction is acidic,

Sugar - no,

Epithelium - 1-2 units per field of view,

Leukocytes - 1-2 in the field of view,

Red blood cells - no.

Biochemical blood test (3 days after surgery):

Total protein - 69 g/l,

Urea - 8.3 mmol/l,

Creatinine - 65 µmol/l,

Bilirubin - 6.1 mmol/l,

ALT - 29 IU/l,

AST - 31 IU/L,

Pancreatic amylase - 15 IU/l,

Complete blood count (3 days after surgery):

Erythrocytes - 4.23×10 ¹² /l,

Leukocytes - 8.9×10 ⁹ /l,

Band neutrophils - 8%,

Segmented neutrophils - 56%,

Lymphocytes - 15%,

Monocytes - 4%,

ESR - 23 mm/h.

Leukocytosis in the blood on the 3rd day significantly decreased, and a decrease in ESR was also noted, starting from the 4th day.

As a result of lymphotropic therapy administered in the postoperative period, the amount of fluid excreted from the abdominal cavity began to decrease, beginning on the second day after surgery. Based on the positive dynamics of the patient's condition and laboratory monitoring data, lymphotropic therapy was administered twice daily for 5 days.

The postoperative period was uneventful: the subhepatic drainage was removed on the third day, and the left lateral drainage on the fourth. The endomesenteric drainage was removed on the fifth postoperative day, and the pelvic drainage on the sixth. The patient was discharged in satisfactory condition on the eighth postoperative day.

The proposed invention has the following advantages compared to the prototype and other known technical solutions:

- increasing the effectiveness of treatment of patients with acute surgical pathology;

- significant acceleration of regression of purulent-septic complications;

- rapid reduction of intoxication in patients;

- reducing the risk of postoperative complications;

- reduction of hospitalization periods;

- faster recovery of working capacity.

- the use of the developed method allows for the improvement of key indicators of quality of life: physical, emotional and social functioning, and an increase in the daily activity of patients.

Bibliography:

1. Andreevskaya M.V. Pumping function of lymphangion under the influence of antibiotics, their solvents and lymphostimulating substances, 1995. https://medical-diss.com/medicina/nasosnaya-funktsiya-limfangiona-pod-vliyaniem-antibiotikov-ih-rastvoriteley-i-limfostimuliruyuschih-veschestv.

2. Buyanov VM, Danilov KYu, Radzikhovskiy AP Drug saturation of the lymphatic system. Kiev: Naukova Dumka; 1991. (In Russ.).

3. Borodin YuI, Lubarskiy MS, Morozov VV Handbook of Clinical Lymphology. Moscow: MIA; 2010. (In Russ.).

4. Borodin Yu.I., Trufakin B.A., Lyubarskiy M.S. Essays on clinical lymphology. Novosibirsk. 2001. (In Russ.).

5. Vtorenko VI, Yesipov AV, Musailov VA, Shishlo VK. Complex NO- and lymphatic therapy in the treatment of peritonitis of various etiologies. Moscow surgical journal. 2012; 28(6): 5-20.

6. Vyrenkov YuE, Vtorenko VI. Lymphological methods in complex treatment of surgical pathology. Annals of surgery. 1996; 1:50-54.

7. Vyrenkov Yu.E. Sepsis: diagnosis and treatment. M. 2010. Vyrenkov YuE. Sepsis: diagnosis and treatment. M. 2010. (In Russ.).

8. Efimenko N.A., Chernekhovskaya H.E., Vyrenkov Yu.E. Guide to Clinical Lymphology. M. 2001. Yefimenko NA, Chernekhovskaya NE, Vyrenkov YuYe. Rukovodstvo po klinicheskoy limfologii. M. 2001. (In Russ.).

9. Levin Yu.M. Fundamentals of therapeutic lymphology. Moscow: Medicine; 1986. (In Russ.).

10. Colon Cancer: Practical Recommendations. Second Edition. Study Guide. Edited by V.P. Petrov, R.V. Orlova, V.A. Kashchenko. - St. Petersburg. - 2014.

11. Egamov Yu.S., Ruziev A.E., Khaidarov S.A. Endomesenteric lymphotropic therapy for abdominal surgical pathology in the postoperative period. Moscow Surgical Journal, 2022. No. 1. P. 69-74 https://doi.org/10.17238/2072-3180-2022-1-69-74.

12. Lymph node dissection in curative gastrectomy for advanced gastric cancer. Tamura S, Takeno A, Miki H - Int J Surg Oncol (2011).

Claims (1)

A method of endomesenteric lymphotropic therapy in the treatment of widespread peritonitis in the postoperative period, including the installation of endomesenteric drainage, the use of drugs, characterized in that the endomesenteric drainage contains an antireflux valve and polyvinyl chloride catheters at a distance of 2 cm from the mesenteric edge of the intestine, the first of which is installed in the mesentery of the right part of the large intestine, the second - in the mesentery of the transverse colon, the third catheter - in the mesentery of the left part of the large intestine; lymphotropic therapy is performed through the endomesenteric drainage, during which Lidase is administered in the amount of 16 U or 32 U, diluted in 2 ml of 0.025% novocaine; heparin is administered in the amount of 0.1-10 U / ml; Derinat is administered in a volume of 5 ml every other day for 10 days; then, after 10 minutes, Ceftriaxone is administered in an amount of 2 grams per day.