RU2594512C1 - Method for intraportal ozone therapy in patients with widespread peritonitis - Google Patents

Abstract

FIELD: medicine.

SUBSTANCE: invention refers to medicine, namely to surgery, and can be applied to intraportal ozone therapy in patients with widespread peritonitis. Ozonation is carried out by means of medical ozone generator with ozone concentration in ozone-oxygen mixture not less than 1,000 mcg/l. After eliminating source of peritonitis, carrying out naso-intestinal intubation, irrigation, and drainage of abdominal cavity, before closure of middle wound, recanalisation and catheterisation of umbilical vein is performed with cannulation. Then intraportal infusion of ozonised perfluoran is performed on days 1 and 2 after operation by drop method at rate 40 drops per minute. Then on days 3 to 5 intraportal infusion is performed with ozonised physiological saline.

EFFECT: method ensures reduction of endogenous intoxication in patients with diffuse peritonitis and reduced number of postoperative complications and postoperative mortality.

1 cl, 3 tbl, 5 dwg, 1 ex

Description

The invention relates to abdominal surgery and can be used to treat patients with acute abdominal organs pathology complicated by the development of peritonitis widespread as a method for correcting liver functional insufficiency in complex treatment.

At present, it is generally recognized that in the mechanism of complex general pathophysiological reactions with widespread peritonitis, the leading role is given to endogenous intoxication. Despite the systemic nature of the disorders, their versatility and interconnectedness, the main sources of endotoxicosis in peritonitis are the abdominal cavity and intestines, which are in a state of persistent paresis in conditions of violation of its protective and barrier function [1, 2].

The liver is one of the main detoxifying systems of the body. A decisive role in the pathogenesis of damage to highly specialized hepatocytes belongs to impaired intrahepatic circulation and hypoxia, while damage to the hepatic macrophages is most associated with a massive inflow of toxic agents from the gastrointestinal tract into the liver through the portal channel [3].

Damage to hepatocytes and the development of liver cell failure leads mainly to a violation of the metabolic function of the liver, which is characterized by a decrease in protein synthesis (primarily albumin), an increase in the production of acute phase proteins, inhibition of oxidation of energy substrates, accompanied by activation of gluconeogenesis and the accumulation of under-oxidized toxic metabolites [ four]. The defeat of a significant part of stellate reticuloendotheliocytocytes under conditions of portal bacteremia and toxinemia leads to the formation of macrophage liver failure, characterized by a violation of the reticuloendothelial barrier of the liver, a “breakthrough” of toxic agents into systemic hemocirculation, which determines the development of toxic-septic shock and progression of endotoxin. In this case, a violation of the barrier (macrophage) function of the liver under conditions of depletion of the reserves of its reticuloendothelial system is currently regarded as a more dangerous form of liver failure and is considered as one of the main criteria in assessing the prognosis of the course and outcome of peritonitis [5].

Currently, the pathogenetic basis of the program for the rehabilitation of the detoxifying system of the liver with widespread peritonitis is made up of the methods of intraportal (transumbilical) therapy. In this case, targeted intraportal administration of various drugs (antibiotics, anticoagulants, antiplatelet agents, antioxidants, antihypoxants, amino acids, etc.) is carried out, affecting various pathogenetic mechanisms of liver damage [6, 7].

One of the promising directions in the complex treatment of common peritonitis is the use of drugs that simultaneously affect several of the most significant links in the pathogenesis of the development of functional liver failure, among which the most important are hypoxia, impaired intrahepatic blood flow, portal bacteremia and endotoxinemia. Such drugs include the domestic product based on perfluorocarbon emulsions - perfluorane.

Perfluorocarbon preparations were originally developed for use as blood substitutes with gas transport functions. In the future, these drugs revealed additional biological properties that expand the scope of use of these drugs. One of their additional properties was the ability to exert a therapeutic effect on the course of infectious and inflammatory processes with regional use. A large number of experimental and clinical studies indicate the high efficiency of intraperitoneal administration of perftoran in the complex treatment of common peritonitis [8-14]. There are also indications of the possibility of correcting intestinal disturbances in the case of enteral use of perftoran in patients with advanced peritonitis [15]. According to most researchers, perftoran in the complex therapy of peritonitis widespread has a multifaceted effect: it carries oxygen and carbon dioxide, improves peripheral blood flow and microcirculation in organs, reduces tissue hypoxia, and also activates the system of mononuclear phagocytes and factors of non-specific humoral immunity [16].

Currently, studies have appeared that indicate the possibility of increasing the therapeutic effectiveness of perftoran by saturating it with medical ozone. As is known, the effect of ozone on the body consists in improving the transport mechanisms of oxygen and increasing its utilization, reducing tissue hypoxia, activating mononuclear cells and stimulating phagocytosis, enhancing a specific and non-specific immune response, as well as detoxifying, bactericidal and anti-inflammatory effects [17]. At the same time, a number of studies have been carried out indicating the high solubility and physicochemical stability of ozone in organo perfluorine compounds [18, 19]. In this case, perfluoran saturated with ozone, due to the total synergistic effect of both drugs, has a longer and more active effect on biological substrates. According to numerous researchers, perfusion of the abdominal cavity with ozonized perfluorane with widespread purulent peritonitis has a pronounced sanitizing, detoxification and anti-inflammatory effect, accompanied by activation of peritoneal macrophages and non-specific resistance factors [20-24].

Given the many-sided and pronounced effect of ozonated solutions, to a greater extent perfluorane, on various metabolic links and pathogenetic mechanisms in infectious and inflammatory pathologies, it seems quite reasonable and appropriate to use these drugs by introducing them intraportally in order to detoxify and correct functional liver failure during complex intensive care in patients with advanced peritonitis. Despite the consistency of such an assumption, there is no literature data on the use of ozonized solutions and perfluorane through its introduction directly into the portal channel of the liver in the treatment of patients with advanced peritonitis.

From the patent literature, a method of ozone therapy for peritonitis is known. According to this method, saline is injected into the abdominal cavity during surgery. The solution is bubbled with ozone directly in the abdominal cavity until a therapeutic concentration is reached. In the postoperative period, ozonized saline is administered through a drainage tube located in the pelvic cavity 2-4 times a day and intravenously at therapeutic concentrations for 8-10 days (see Russian patent No. 2122835, publ. 10.12.1998, cl. A61B 17/00).

In our opinion, the main disadvantage of this method is that ozonated solutions are administered intraoperatively into the abdominal cavity with the subsequent use of ozonated solutions intravenously, since it has been proven that the greatest significance in the regulation of the activity of the reticuloendothelial system of the liver with widespread peritonitis belongs to the portal bacteriotoxemia syndrome [25].

The liver is the first barrier and target organ in the path of various toxic products coming from the abdominal cavity and intestinal lumen into the systemic circulation. The increasing toxic effect on the liver with the progression of the abdominal infectious and inflammatory process leads to the development of liver failure and is accompanied by a significant decrease in the antitoxic function of this organ. In this connection, the method of intraportal administration of ozonized physiological solutions and perfluorane proposed by us is pathogenetically substantiated.

The advantages of intraportal administration of drugs are due to the following: drugs are brought to the liver parenchyma in a chemically unchanged form in a sufficiently high concentration; direct contact of drugs with liver cells is achieved; at the level of the liver parenchyma, toxic products are bound both to those formed in the liver and from the intestinal lumen.

Object of the invention: improving the effectiveness of treatment of patients with advanced peritonitis by intraportal administration of ozonated perftoran and saline.

The technical result of the invention is to improve splanchnic hemodynamics and oxygenation of portal blood, as well as reducing endogenous intoxication in patients with advanced peritonitis.

The problem is solved in that the method of intraportal ozone therapy for common peritonitis, including complex treatment, is characterized by the intraportal administration of ozonated perftoran and physiological saline.

In this case, ozonation is carried out by means of a medical ozonator, with an ozone concentration in the ozone-oxygen mixture of at least 1000 μg / L. After eliminating the source of peritonitis, conducting nasointestinal intubation, lavage and drainage of the abdominal cavity before suturing the median wound, recanalization and catheterization of the umbilical vein with its cannulation for intraportal infusion with ozonated perfluorane in 1-2 days after the operation is carried out dropwise in drops of 40 drops in 1 min. After that, portal blood is monitored to assess the functional state of the liver: bilirubin, protein, albumin, ALT and ACT activity. Portal blood oxygenation and ultrasound control are also carried out with an assessment of the rate of hepatic blood flow. Then, for 3-5 days, intraportal infusion is carried out with ozonized physiological saline, with the above monitoring scheme.

The use of intraportal administration of ozonated perftoran in the early postoperative period in patients with advanced purulent peritonitis leads to an improvement in splanchnic hemodynamics and oxygenation of portal blood to a greater extent than the introduction of conventional ozone-saturated solutions into the superior vena cava system and systemic blood flow, and also leads to the leveling of clinical and laboratory manifestations of endotoxemia, which contributes to the rehabilitation of functional liver failure and improves direct e results of surgical treatment.

The invention is illustrated by the following drawings, where:

In FIG. 1 shows the mobilization of the umbilical vein.

In FIG. 2 - recanalization of the umbilical vein.

In FIG. 3 - umbilical catheter.

In FIG. 4 - the final view of the postoperative wound with a fixed catheter to the anterior abdominal wall.

In FIG. 5 - a method of ozonation of saline and perfluorane.

A detailed description of the method and an example of its clinical application

Surgical allowance is carried out under endotracheal anesthesia. After performing a wide median or transverse laparotomy, a thorough revision of the peritoneal cavity and retroperitoneal space from the abdomen is performed.

диаметра пересекают пупочную вену. Края вены берут сосудистыми зажимами. Удерживая зажимы, в просвет вены вращательно-поступательными движениями вводят увлажненный маточный зонд диаметром 3 мм по направлению к воротам печени, до ощущения "провала" (фиг. 2). Затем, в просвет вены вводят специальный катетер №8 или №10 с заглушкой, вытянутым дистальным концом и тремя боковыми отверстиями (фиг. 3). Шприцем из воротной вены забирают для бактериологического исследования 2 мл портальной крови и немедленно отправляют в лабораторию. В катетер медленно вводят 20 мл 0,25% раствора новокаина, одновременно завязывая дистальную держалку, концы которой не срезают, так как в последующем они выводятся и фиксируются на передней брюшной стенке. Проксимальную держалку также завязывают, а свободные концы срезают. До катетера, отдельными швами, ушивают рассеченную брюшину круглой связки печени. Катетер выводят через лапаротомную рану на переднюю брюшную стенку и фиксируют к ней отдельными швами. Свободные концы дистальной держалки фиксируют на марлевом шарике и оставляют на передней брюшной стенке (фиг. 4).After eliminating the source of peritonitis, conducting nasointestinal intubation, lavage and drainage of the abdominal cavity before suturing the median wound from the round ligament of the liver, the umbilical vein that goes to the gate of the liver is isolated. After dissection of the peritoneum, the umbilical vein is mobilized for at least 3 cm (Fig. 1). Two nylon filaments are brought under the vein, between which, in the transverse direction on $$\raisebox{1ex}{$\mathrm{one}$}\!\left/ \!\raisebox{-1ex}{$2$}\right.$$

diameter cross the umbilical vein. The edges of the vein take vascular clamps. Holding the clamps, a moistened uterine probe with a diameter of 3 mm in the direction of the gate of the liver is inserted into the lumen of the vein by rotational-translational movements until the sensation of "failure" (Fig. 2). Then, a special catheter No. 8 or No. 10 is inserted into the lumen of the vein with a plug, an elongated distal end and three lateral openings (Fig. 3). With a syringe from the portal vein, 2 ml of portal blood is taken for bacteriological examination and immediately sent to the laboratory. 20 ml of a 0.25% solution of novocaine are slowly injected into the catheter, at the same time tying a distal holder, the ends of which are not cut, since subsequently they are removed and fixed on the anterior abdominal wall. The proximal holder is also tied, and the free ends are cut off. To the catheter, in separate sutures, the dissected peritoneum of the round ligament of the liver is sutured. The catheter is removed through the laparotomy wound to the anterior abdominal wall and fixed to it with separate sutures. The free ends of the distal holder are fixed on a gauze ball and left on the anterior abdominal wall (Fig. 4).

Further, in the early postoperative period (1-3 days), we infused ozonated solutions and perfluorane according to the following procedure.

Ozonation of saline and perfluorane is carried out by bubbling it with an ozone-oxygen mixture (i.e., the ozone-oxygen mixture is passed through saline and perfluorane through a polyvinyl chloride tube, Fig. 5-2) for 15-20 minutes at a rate of 0.5 l / min with an ozone concentration of 800-1000 μg / l. For this procedure, factory bottles with perfluorane and physiological saline were used (Fig. 5-3), another sterile empty bottle (Fig. 5-5) with a capacity of 400 ml, corked with a rubber cap and crimped with an aluminum cap. To do this, we used an ordinary bottle with physiological saline, after emptying it with a sterile syringe. The perfluorane vial was connected to an empty sterile vial using a polyvinyl chloride tube with two needles at the ends (Fig. 5-4), introducing needles: one into the vial with perfluorane and the other into an empty, sterile vial. In this case, the tube for discharging the used gas mixture to the ozone destructor does not exit from the solution bottle, but from another empty bottle connected to it, as shown in FIG. 5 (Figs. 5-4 and 5-5), which prevents the ozonized solution and perfluorane from entering the destructor (Figs. 5-6). To obtain the ozonized solution and perfluorane, the Medozons-BM ozonizer of the company Arzamas Instrument-Making Plant OJSC was used.

When calculating the dose of ozone introduced to the patient, it was taken into account that the concentration of ozone dissolved in physiological saline is on average 20% of the concentration of ozone in the bubbling solution of the gas mixture, i.e., the conversion factor is 0.2. This means that, for example, when the concentration of ozone in the ozone-oxygen mixture is 1000 μg / L in 1 liter of physiological solution, 0.2 × 1000 = 200 μg O3 will dissolve (calculation error is not more than 10%).

Intraportal infusion with ozonated perfluorane was carried out 1-2 days after the operation by the drip method of 40 drops per 1 min. Accordingly, portal blood was monitored to assess the functional state of the liver: bilirubin, protein, albumin, ALT and ACT activity, oxygen saturation of portal blood, as well as ultrasound control with an assessment of the speed of hepatic blood flow. Then, for 3-5 days, intraportal infusion was carried out with ozonized physiological saline, with the above monitoring scheme. With an improvement in the general condition of the patient, a negative result of bacteriological blood tests from the portal system for anaerobic microorganisms (5-6 days after surgery), the introduction of ozonated solutions was stopped. The umbilical vein catheter was stored for the administration of glucose-electrolyte solutions, vitamins, blood substitutes, and then removed in compliance with aseptic rules and measures to prevent bleeding from the recanalized umbilical vein.

Evaluation of endotoxemia was carried out on the basis of clinical parameters and laboratory criteria (LII, SMP, myoglobin, urea and creatinine content). The severity of the systemic inflammatory reaction was evaluated by the level of protein content of the acute phase of inflammation (CRP, fibrinogen). Assessment of the functional state of the liver was carried out by indicators of the level of total bilirubin, protein, albumin, ALT and AcT activity.

As can be seen from table 1, the initial manifestations of endogenous intoxication in the studied groups were maximum, which corresponded to the pronounced phenomena of endotoxemia and liver failure. Against the background of pathogenetically directed therapeutic measures, including intraportal infusion of ozonized physiological saline, a distinct positive dynamics is noted, starting from the first postoperative days and reaching a maximum by the fifth day. So, C-reactive protein in patients of group I by day 5 reached 164.9 ± 3.1 mg / l, and in group II of the study, it was 123.5 ± 2.9 mg / l.

Judging by the results presented in table 2, against the background of pathogenetically directed therapy of macrophage liver failure, there was a pronounced decrease in the level of "blood slag" in patients of group II, compared with the control study group. So, on the 5th day of the postoperative course, the creatinine level in patients of group I reached an average of 121.2 ± 4.0 μmol / l, while in patients of group II this indicator decreased to 98.9 ± 3.1 μmol / l. Urea in patients of group I on the 3rd day of the postoperative period reached 16.4 ± 0.3 μmol / l, and in the second, studied group, it decreased to 11.2 ± 0.1 μmol / l.

From the data presented in table 3, it follows that against the background of the introduction of ozonized physiological saline, there was a clear decrease in the indicators of endogenous intoxication, in the control group more than 2 times by the fifth postoperative day.

Clinical example. Patient A., 75 years old, was admitted to the clinic on the 8th day from the onset of the disease with a diagnosis of Acute destructive appendicitis? peritonitis? OKN ?, endotoxicosis of the II degree, c-g of the bladder T1N0M0, condition after TUR. HIBS, coronary cardiosclerosis. Upon admission, the patient's condition is severe (on a SAPS scale of 5–9 points, prognostic mortality of 7.9%, Glasgow severity rating is 14), the patient is sluggish, the skin is pale pink in color, covered with cold sweat. In the lungs on both sides, hard breathing, no rales. NPV 19 per minute. Blood pressure 130/90 mm RT. Art., heart rate of 90 per minute. The tongue is dry, coated with a gray coating, the stomach is evenly swollen. On palpation, the abdomen is sharply painful in all departments, mainly in the lower sections (left and right iliac regions), tense. The positive symptoms of peritoneal irritation are determined. Percussion over the entire surface of the abdomen is determined by tympanitis, auscultatory - peristalsis is sharply weakened. In the general analysis of blood leukocytosis 15.2 × 10%, LII = 10.1 calc. units, urea 12.5 mmol / L, creatinine 224 μmol / L, bilirubin 34.1 μmol / L. With laparotomy in the peritoneal cavity up to 2000 ml of purulent-fibrinous effusion, attention is paid to soldered together by loose adhesions, expanded to 6 cm, loops of the small intestine, the presence of sequestered fluid is noted in the lumen, there is no peristalsis. In the right iliac fossa, the vermiform appendix is visualized, enlarged, strained, perforation at the base up to 0.2 cm. Appendectomy was performed. After blockade of the mesentery root of the small intestine with 0.25% novocaine solution in an amount of 100 ml, total nasointestinal intubation with intraoperative enterosorption was performed. Recanalization and catheterization of the umbilical vein with its cannulation was performed. On the second day after the operation, intraportal infusion was carried out by the drip method with ozonized perfluorane, 40 drops per 1 min. Accordingly, portal blood was monitored to assess the functional state of the liver: bilirubin, protein, albumin, ALT and ACT activity, oxygen saturation of portal blood, as well as ultrasound control with an assessment of the speed of hepatic blood flow. Then, on the third day, intraportal infusion was carried out with ozonized physiological saline, with the above monitoring scheme.

The patient was transferred to the intensive care unit for intensive infusion, antibacterial, detoxification therapy, intestinal lavage with enterosorbents, early enteral tube feeding. By the 4th day, the patient's condition stabilized, signs of endogenous intoxication significantly decreased (BP 131/89 mm Hg, heart rate 91 per minute, NPV 22 per minute, LII 5.25 calculation units, urea 11.1 mmol / l., creatinine 97 μmol / l, bilirubin 7.5 μmol), intestinal paresis persisted. By the 6th day, the patient's condition improved significantly (blood pressure 130/80 mm Hg. Art., Heart rate 80 per minute, NPV 16 per minute, LII 5.0 calculated units, urea 10.0 mmol / l., Creatinine 121 μmol / l), active peristalsis, gases go away. The amount of discharge through the nasointestinal probe decreased significantly. The probe has been deleted. Drainage tubes removed 5 days from the time of surgery. The patient was discharged 15 days after surgery. The outcome is recovery.

The proposed method of treatment was tested by us for 17 patients with peritonitis, seven of whom ozonated perfluorane was administered on the 1-2 postoperative day, while the mortality in this group was only 12.5%, which significantly exceeds the average statistics for this pathology.

The proposed method allows to improve the treatment results of patients with advanced peritonitis.

The claimed method of treatment in complex therapy in patients with advanced peritonitis has been tested on sufficient clinical material, has shown its effectiveness and can be recommended for use in specialized surgical hospitals.

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Claims (1)

A method of intraportal ozone therapy for widespread peritonitis, including complex treatment, characterized by intraportal administration of ozonated perfluorane and physiological saline, while ozonation is carried out by means of a medical ozonizer, with an ozone concentration of at least 1000 μg / l in the ozone-oxygen mixture; after elimination of the source of peritonitis, nasointestinal intubation, lavage and drainage of the abdominal cavity before suturing of the median wound, recanalization and catheterization of the umbilical vein with its cannulation for intraportal infusion with ozonized perfluorane in 1-2 days after the operation is carried out dropwise 40 drops in 1 min after what is monitoring portal blood; then for 3-5 days an intraportal infusion is carried out with an ozonized physiological solution with the above monitoring scheme.

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