EA007473B1 - Method for treating pancreatitis - Google Patents

Abstract

It is suggested a method of pancreatitis treatment through celiac trunk catheterization and conduction of continuous regional arterial infusion of a medicinal solutions complex on the basis of an antibiotic and an antifermental preparation in which as a medicinal solutions complex, at least, one, cytoprotective complex comprised by, at least, one broad spectrum antibiotic, at least, one antioxidant, at least, one anticytokine preparation, at least, one antihypoxant and as an antifermental preparation, at least, one antiphospholipase preparation are entered, the said complex being entered continuously within 5-7 days.It is also suggested a method of prevention of septic complications maintenance of acute pancreatitis necroticans through superior mesenteric artery catheterization and conduction of continuous regional arterial infusion of a medicinal solutions complex on the basis of an antibiotic and an antifermental preparation in which as a complex of medicinal solutions, at least, one, cytoprotective complex comprised by, at least, one broad spectrum antibiotic, at least, one antioxidant, at least, of one anticytokine preparation, at least, one antihypoxant and as an antifermental preparation, at least, one antiphospholipase preparation are entered, the said complex being entered continuously within 5-7 days.

Description

The invention relates to the field of medicine, namely to the treatment of acute necrotizing pancreatitis by regional intraarterial infusion into the celiac trunk of a combination of drugs capable of interrupting a cascade of pathogenetic reactions and stabilizing the action of already formed endotoxins in order to remove or bind the latter.

The invention also relates to a method for the prevention of septic complications of acute necrotizing pancreatitis by regional intraarterial infusion into the superior mesenteric artery of a combination of drugs capable of exerting a preventive effect against infection of necrotic pancreatic tissue and retroperitoneal tissue.

In acute pancreatitis, it is extremely important to quickly and accurately assess the severity of the patient’s condition and to optimize and coordinate the drug and surgical treatment programs. Since necrosis of pancreatic and peripancreatic tissues occurs early in the course of the disease, within the first 1-2 days, it is customary to begin drug treatment, including antibiotic therapy, since the patient was hospitalized. For the purposes of drug treatment, a large number of treatment methods have been developed using various drug complexes based on antibiotics and anti-enzyme drugs.

There is a method for the treatment of acute pancreatitis by catheterization of the celiac trunk with the introduction of solutions of novocaine, heparin, kontakala, 5-fluorouracil, antibiotics and atropine [R.! R. R., U.1.Cowa K., A. Ζυηζον I., ZakakikYV.1. 1a1te1 tebyub ίη asi! E rapsgeaiSh. Kygygdna (8GNA), 1998; 51 (3): 14-15.].

There is a method of treating acute pancreatitis by catheterization of the gastric arteries and continuous regional arterial infusion of medicinal solutions of actiprotease drugs in combination with antibiotics [Takeba K., Uatansy 1, 81Niua K. e! a1. Wild Giant Family TeduPa1 aPePa1 1GHI δίοη oG rgodiagé shyyog apb apyubs sh! 1e tapadedep! og asi! e pesgoShshd rapsteabbk. Rapsgea! 2001; 1: 668-673.].

Known use of biospecific hemosorption on Ovosorb in the treatment of acute pancreatitis [Martov Yu.B., Kirkovsky VV, Martov V.Yu. Acute destructive pancreatitis .- M .: Slow., 2001. p.49-51.].

It is known the use of intramuscular and intravenous emoxipin in the complex treatment of acute pancreatitis as an antioxidant [Dubinsky N.V. Clinical and pathogenetic rationale for the use of the antioxidant emoxipin in acute pancreatitis: author. dis. Cand. honey. Sciences: 14.00.27 / Ukr. in-t improved doctors - Kharkov, 1991, 24 s].

At the same time, acute necrotizing pancreatitis is usually accompanied by septic complications, which complicates the process of treating the patient and leads to additional risks. In this regard, various methods of preventing septic complications of acute pancreatitis by early intravenous infusion of antibiotics, intra-arterial infusion of antibiotics into the pancreatic necrosis zone, selective bowel decontamination are also known [1, 2, 3, 4, 5, 6].

All the above-mentioned methods mainly involve the continuous infusion of a complex of medicinal solutions, including antibiotics and antifermental preparations. However, these drugs are usually not enough to ensure highly effective treatment and, above all, to prevent the development of septic complications.

The introduction of antibiotics that, along with a broad spectrum of bactericidal action, have good penetration into the pancreas is generally accepted. The drugs that meet these requirements are imipenem, meronem, cephalosporin III and IV generation, ciprofloxacin, etc. [1, 7]. The introduction of antibiotics in the celiac trunk involves the creation of high local concentrations in the pancreas and increasing the effectiveness of antibiotic therapy.

The disadvantages of intravenous administration of antibiotics and intraarterial in the celiac trunk is the lack of a selective effect on the source of infection and on the mechanism of microorganism penetration into the human body. Selective intestinal decontamination in acute pancreatitis changes the composition of the intestinal flora in favor of gram-positive, to a lesser extent, affecting the frequency of septic complications.

Gram-negative microorganisms are found overwhelmingly in infected tissues in acute pancreatitis, which suggests their gastrointestinal origin, and bacterial translocation is a mechanism of penetration [8, 9, 10]. Abnormally increased permeability of the intestinal wall for micro and macromolecules, is the basis of the modern theory of the role of the intestinal barrier in the development of multiple organ failure and sepsis in acute pancreatitis. The phenomenon of increased intestinal permeability, well studied in experimental and clinical studies, is characteristic of the first 2–4 days of the disease and closely correlates with endotoxemia, the severity of the disease and the risk of septic complications [11]. In some experimental studies on rats and dogs, the positive effect of pentoxifylline on reducing the massiveness of bacterial translocation and intraarterial administration of antibiotics to the superior mesenteric artery on the development of septic complications and the risk of death was proved [12, 13]. The dependence of bacterial translocation on the energy state of the enterocyte, and intestinal permeability on

- 1 007473 ischemia of the intestinal mucosa [14, 16]. Energetically depleted enterocyte does not prevent the translocation of bacteria, not only paracellular, but also transcellular [15]. This indicates the critical role of the state of microcirculation and oxygen delivery in the barrier function of the intestinal wall. There are clinical data on the absence of DNA and RNA of microorganisms in the blood plasma of patients with acute pancreatitis, in whose blood endotoxin is detected, and there are markers of increased translocation [17].

Accumulated data indicate the functional insufficiency of the intestinal barrier in the early stages of acute pancreatitis and the need to influence the maintenance of its properties to prevent bacterial translocation.

Thus, the object of the invention is to provide a method for treating pancreatitis and a method for preventing septic complications of acute necrotizing pancreatitis, which would ensure higher efficacy of treatment and prevention, including by ensuring long-term maintenance of the intestinal barrier function in acute pancreatitis during the period of the disease, the most critical for penetration of microorganisms into parapancreatic tissues and pancreatic tissue from the intestinal lumen. The inventive methods, in addition, should ensure a reduction in the mortality rate in patients with acute necrotizing pancreatitis and reduce, to the extent of exclusion, the risk of septic complications of acute necrotizing pancreatitis.

To solve this problem, it was necessary to satisfy a number of conditions: ensuring continuity of drug exposure to the lesion, choosing a method of drug delivery to increase the selectivity of exposure and creating the highest local concentrations, choosing drugs that improve oxygen delivery to tissues that have anti-inflammatory and antibacterial effects, etc. ..

The problem is solved by a method of treating pancreatitis by catheterizing the celiac trunk and carrying out continuous regional arterial infusion of a complex from medicinal solutions based on an antibiotic and antifermental preparation, in which at least one cytoprotective complex composed of at least one antibiotic is administered as a complex of medicinal solutions, at least one antioxidant, at least one anti-cytokine drug, at least one antihypoxant, and in anti-enzyme preparation of at least one antiphospholipase preparation, while the complex is administered continuously for 5-7 days.

The task is also solved by a method for the prevention of septic complications of acute necrotizing pancreatitis by catheterization of the superior mesenteric artery and carrying out a continuous regional arterial infusion of a complex from medicinal solutions based on an antibiotic and an antienzyme preparation, in which at least one cytoprotective complex composed according to at least one antibiotic, at least one antioxidant, at least one anti-cytokine drug, at least one antihypoxic drug and, as an anti-enzyme drug, at least one anti-phospholipase drug, while the complex is administered continuously for 5-7 days.

In the course of the research, the authors found that these complexes of the same composition, delivered through the celiac trunk and through the superior mesenteric artery, contribute in the first case to creating maximum concentrations of drugs in the pancreatic tissue, which is extremely important from the point of view of the treatment process, and in the second case - strengthening the intestinal wall, thereby preventing septic complications.

Also, experimentally selected preferred forms of implementation of the proposed methods, which does not exclude the achievement of good results in treatment and prevention when using other drugs within the stated classes.

Preferred are the implementation forms of the inventive methods, in which cytoprotective complex I is administered as a cytoprotective complex, in which a third or fourth generation cephalosporin solution is chosen as an antibiotic, emoxipine solution is chosen as an antioxidant, diavitol solution is chosen as an antihypoxic drug, and pentoxifylline, as an antiphospholipase drug choose emoxipine solution.

Also preferred are the implementation forms of the inventive methods, in which cytoprotective complex II is administered as a cytoprotective complex, in which a solution of cephalosporin III or IV generation is chosen as an antibiotic, an emoxipine solution is chosen as an antioxidant, diavitol solution is chosen as an antihypoxicant, an anti-cytokine drug is chosen as an antioxidant pentoxifylline, and as the antiphospholipase drug choose lidocaine.

In another form of implementation of the proposed methods as a cytoprotective complex injected cytoprotective complex III based on cytoprotective complex I and at least one drug that regulates metabolic processes of cells.

And, finally, in another form of implementation of the claimed methods, a cytoprotective complex IV is administered as a cytoprotective complex based on a cytoprotective complex II and at least one drug that regulates cellular metabolic processes.

- 2 007473

The preferred drugs that regulate the metabolic processes of cells may include diavitol.

In some cases, the implementation of the proposed method of treating pancreatitis and the method of preventing septic complications of acute necrotizing pancreatitis, it may be preferable to administer one after one different cytoprotective complexes as a complex of medicinal solutions, in particular the above-mentioned complexes I, II, III, IV, and prior to their introduction the program of introduction, with this set as the sequence of introduction of the complexes, and the number of repetitions of the introduction of each complex.

In various forms of realization of the claimed methods, diavitolgel, either omegatrien, or diavitol-gel and omegatrien, is additionally injected through the probe.

In the inventive methods, a cytoprotective complex proposed and compiled by the authors for the first time, in which a broad spectrum antibiotic is chosen as an antibiotic, for example, generation III or IV cephalosporins or tinamy, etc., emoxipin is preferably chosen as an antioxidant, pentoxifylline is preferably chosen as an antioxidant , diavitol is preferably chosen as an antihypoxic drug, and antiphospholipase preparation, such as lidocaine or emoxipin, is preferred as an anti-enzyme preparation, Injected with an infusion pump continuously for 5-7 days through an angiographic catheter installed at the mouth of the superior mesenteric artery (for the prevention of septic complications) 1-2 days after admission of a patient with severe acute pancreatitis.

Protecting the pancreas, and therefore the patient, from catastrophe can only interrupt the key links in the cascades of pathogenetic reactions. Therefore, along with the traditionally used drugs, drugs with antioxidant, antiphospholipase and antihypoxic properties were included in the therapy complex.

Of the antioxidants widely used in clinical practice, the authors chose emoxipin. This drug is a derivative of 3-hydroxypyridine and is a universal synthetic antioxidant. In addition, emoxipin stabilizes membrane structures, inhibits platelet aggregation and inhibits the transfer of fibrin monomer to fibrin polymer [Antioxidant therapy of acute pancreatitis / R. B. Mumladze, S. M. Chudnykh, IT T. Vasilyev, E. P. Tuvina // Annals of Surgery. 1997, №1, p. 67-70; Dubinsky N.V. Clinical and pathogenetic rationale for the use of antioxidant emoxipin in acute pancreatitis: author. dis. ... Cand. honey. sciences. 14.00.27 / Ukr. in-t improved doctors Kharkiv, 1991; Mashkovsky M. D. Medicinal products. Minsk, Belarus, 1987, p. 2, p. 289-290]. Such a multifaceted effect of emoxipin and its water solubility made it possible to use the drug in the complex therapy of acute pancreatitis, as well as to vary the methods of its targeted delivery.

In addition, as a result of experimental studies by the authors of the present invention, the ability of emoxipin to inhibit the action of phospholipase A2, previously unknown to those skilled in the art, was discovered, which allowed it to be used as part of a complex used in the claimed method, as well as an antiphospholipase preparation. . Since these results imply a fairly broad evidence base, they are issued in the form of a Eurasian application for invention simultaneously filed in the name of the same applicant.

Inhibition of lipolytic activity was also carried out with lidocaine. This drug belongs to acetanilide derivatives and, along with local anesthetic activity, has antiarrhythmic properties that are associated with a stabilizing effect on cell membranes, in particular myocardium. Studies in recent years have also revealed the presence of an antiphospholipase effect in lidocaine (for A2 phospholipase) [Litvinenko N. M., Kisel M. A. Endogenous Phospholipase A2 (structure and functions). Mn., Science and technology, 1991, p.270, Chikinev Yu. V. Use of alfatokoferol and lidocaine in the complex treatment of acute pancreatitis: Author. dis. ... Cand. honey. Sciences: 14.00.27. Novosibirsk, 1995, p. nineteen]. All this made it possible to include this water-soluble drug in the complex therapy of acute pancreatitis and the prevention of septic complications in acute pancreatitis.

The arising hypoxia of the tissues not only of the pancreas, but also of other organs and systems, accompanying acute pancreatitis, was the basis for use in complex therapy for acute pancreatitis of the antihypoxant, in particular, diavitol. The drug is a deproteinized serum hydrolyzate of cow embryos. Its multimodal effect is associated with the content of low molecular weight peptides, amino acids, intermediates of carbohydrate and lipid metabolism, glycolipids, nucleosides, trace elements and other components that have a multifunctional effect. Diavitol regulates energy processes in cells, stimulates trophic and reparative processes. [Eurasian Patent No. 000633, А61К 35/14, Β01Ό 61/14. The method of obtaining a biologically active drug from the blood of cattle and a pharmaceutical composition based on it with radioprotective, antioxidant, immunomodulating, wound healing and anti-herpetic activity / L.V. Plenina, S.V. Khlyustov, N.I. Fedorov et al. No. 199700388; declare 10/16/97; publ. 29.12.99 // Eurasian Patent Office. 1999, p. 1-14]

- 3 007473

Pentoxifylline was used as a means of improving microcirculation, the rheological properties of blood, reducing platelet aggregation and improving the supply of oxygen to tissues. The drug, in addition to the basic properties, has the ability to inhibit pro-inflammatory cytokines.

To correct the proteinase inhibitory imbalance and remove the excess of various biologically active substances appearing in the blood of patients with acute pancreatitis, the authors used biospecific hemosorption on Ovosorb. The antiprotease hemosorbent Ovosorb is an ovomucoid, covalently fixed in a polyacrylamide gel. It has the ability to selectively bind serine proteinases (trypsin, chymotrypsin, plasmin, elastase, etc.).

The above examples of specific drugs at the same time should not be construed as limiting, since other drugs belonging to the above groups and having similar activity are known to the person skilled in the art.

The authors conducted clinical trials of the proposed method, during which they studied the nature of the therapeutic effect of cytoprotective drugs in several groups of patients with different forms of acute pancreatitis.

Conservative-preventive therapy of acute pancreatitis was of a level nature, which was determined on the basis of the clinical and ultrasonographic characteristics of patients. Therefore, all patients were divided into groups according to the severity and timing of initiation of therapy.

Patients with interstitial pancreatitis, in addition to the standard combination therapy, received intravenous cytoprotectors (emoxipin, diavitol, pentoxifylline) and lidocaine intramuscularly. The perfusion rate through the mass exchanger was 40-60 ml / min with a session duration of 120-180 minutes. The choice of the dose of injected drugs was determined by the data obtained from the experimental part of the work. According to these results, the antioxidant drug 1% emoxipin was administered at a dose of 1.5 mg per kg body weight 2 times a day after 12 hours. The antihypoxant diavitol was administered once a day intravenously with an isotonic solution of sodium chloride at a dose of 2 mg per kg body weight. The duration of treatment was at least 7 days. The inclusion of these drugs in the scheme of basic therapy was carried out from the first hours the patient was in the hospital. In some patients, local administration of cytoprotective drugs was carried out.

The control group of patients with interstitial pancreatitis was patients who for one reason or another received only basic treatment.

The level of treatment in the group with necrotizing pancreatitis depended both on the morphological picture obtained when performing computed tomography and ultrasonographic research, and on the score obtained on the estimated severity scale of the patient’s condition, or was proposed by the authors [Eurasian Application No. 200400460 of 03/23/2004].

Patients with necrotizing acute pancreatitis were divided into several groups in which the following treatment was carried out.

1. The complex of cytoprotectors intravenously in doses of 3-10 mg per kg per day after 12 hours.

2. The complex of cytoprotectors intravenously in doses of 3-10 mg per kg of body weight per day after 12 hours in combination with hemosorption on Ovosorb.

3. The complex of cytoprotectors intravenously in doses of 3-10 mg per kg body weight per day after 12 hours and locally to the altered areas of the pancreas. The indications for local administration of these drugs were negative dynamics with dynamic ultrasound and clinical laboratory data, suspicion of infection and with the aim of preventing possible other complications, as well as the need to arrest further spread of destructive processes in the gland. This was carried out both with minimally invasive interventions under ultrasonographic control, and during laparoscopy.

When performing surgical interventions, pancreatic obkalyvaniye was performed during the operation, and then retroperitoneal or intra-salar delivery of drugs with cytoprotective action through microirrigators was performed for 5-8 days.

The control group included 49 patients with acute necrotizing pancreatitis who received only traditional therapy with the inclusion of the anti-protease drug Ovomin. Patients were also divided into two subgroups: with the presence or absence of local complications.

The effectiveness of the nature of the therapeutic effect of various cytoprotective drugs was evaluated according to clinical data, the dynamics of the most significant hematological and biochemical tests (at 1, 3, 7 days and thereafter every 7 days), as well as according to the dynamic ultrasound (invasive and non-invasive).

As noted above, according to the results of experimental studies and practice, the authors chose a cytoprotective complex based on pentoxifylline, diavitol, lidocaine / emoxipin, and third-generation cephalosporin as one of the preferred forms of the invention. According to the authors, the ability of pentoxifylline to change the plasticity of the erythrocyte, improves oxygen delivery, and in doses of more than 300 mg / day, a vasodilator and disaggregation effect is provided. In addition, the ability of pentoxifylline to inhibit the synthesis of the main trigger of proinflammatory cytokine tumor necrosis factor is achieved anti-inflammatory effect, which is complemented by the ability of lidocaine to reduce the activity of phospholipase A2 and the antioxidant properties of emoxipin. In this case, the antibacterial effect is realized by the use of third-generation cephalosporins with a broad spectrum of action and good penetration into the retroperitoneal fat and pancreas.

In general, a method of treating pancreatitis and preventing septic complications of acute necrotizing pancreatitis is as follows.

On the basis of the patient's diagnosis, the scheme of drug treatment and prophylaxis is determined, for which purpose the cytoprotective complexes to be administered, their composition, the sequence of administration, the number of administrations of each complex, doses, etc. In some cases, for the treatment and prevention of a single injection of a single complex.

To ensure continuous delivery of drugs from the composition of the cytoprotective complex (s) under aseptic conditions under local anesthesia with a 0.25% solution of novocaine, the left femoral artery is catheterized according to Seldinger-Edman. Angiographic catheter type "Cobra" with a diameter of 2.5 mm under fluoroscopic control with the introduction of 76% urografin is carried out in the celiac trunk (during treatment) or the superior mesenteric artery (with prophylaxis). On the skin of the thigh a catheter is fixed with a wide sticker of adhesive tape. The catheter is connected to the cannula of the syringe inserted into the infusion pump.

Each drug is injected with an infusion pump from a 10 ml syringe, while solutions of pentoxifylline and emoxipin use ready-made 10 ml each, and dilute the solution of lidocaine and antibiotic in 0.9% NaCl to 10 ml.

Twice during the day, heparin is administered to prevent thromboembolic complications and to maintain the patency of the catheter. The multiplicity, duration and speed of administration are presented in the table.

The multiplicity, duration and speed of drug administration in

The drug dose. Duration of administration, h. The rate of injection, ml / h. Cefalosporin, 1 g 2 five Pentoxifylline, 10 ml 3 3.3 Emoxipin, 1% -10ml 2 five Lidocaine, 2% -4 ml 2 five Cefalosporin, 1 g 2 five Pentoxifylline, 10 ml 3 3.3 Heparin, 5000 Ed. 0.5 20 Emoxipin, 1% -10ml 2 five Lidocaine, 2% -4 ml 2 five Cefalosporin, 1 g 2 five Pentoxifylline, 10 ml 3 3.3 Heparin, 5000 Ed. 0.5 20

Catheterization (celiac trunk or superior mesenteric artery) is performed 1-2 days from the patient’s admission and drugs are administered for 5-7 days, after which, under aseptic conditions, the catheter is removed and a pressure bandage is applied for 12-24 hours. reani mation.

This technique was applied in the treatment of 17 patients hospitalized in the intensive care unit of the 9th city clinical hospital (GKB) in Minsk. The average age in the group is 44 years old [2773], males 9, females 8. The average score of weight is 4.70 Kapsop [1-10]. From 17 patients purulent complications

- 5 007473 nenyi developed in 1 (5.8%), one died on the third day from receipt from the phenomena of multiple organ failure (5.8%).

Below the invention is explained on some examples of implementation, which serve solely to illustrate the advantages and advantages of the proposed method, and not to limit the scope of the claims of the applicant.

Example 1

Patient E., born in 1940, was admitted to the intensive care unit and intensive care unit of the 9th Minsk city clinical hospital with a diagnosis of acute pancreatitis (blood amylase when receiving 640 U).

Clinical diagnosis: Acute necrotizing pancreatitis. Parapancreatitis. Omentobursit.

Objectively: the state is grave. Dyspnea at rest 24 '. Complaints of weakness, encircling pain at the top of the abdomen. Vesicular breathing. The abdomen is swollen, painful in the epigastrium. HELL = 180/100 mm Hg Art., pulse 70 ', temperature 38.1 ° C.

In general, blood tests: Hb 118 g / l, erythrocytes 3.68, leukocytes 15.5, stab 12%, segmented nucleus 70%, lymphocytes 12%, monocytes 2%.

In the biochemical analysis of blood: bilirubin 22 μmol / l, urea 7.5, total protein 56 g / l, glucose 6 mmol / l, ALT 23, AST 26, sodium 152, potassium 6.2, calcium ionized 0.9, chlorides 112

The oxygen partial pressure in capillary blood is 59.7 mm Hg, the buffer bases are 3.7 mmol / l.

The prognostic score of gravity on Jaapzop = 4.

On the day of admission (1st day): ultrasound examination of the abdominal organs: liver + 4.5 cm, homogeneous, echo (+ +), biliary tract is normal. Pancreas 34 - 25 - 27 mm, heterogeneous, echogenicity (+ +), in the head and body areas of destruction of 13 and 37x22 mm, anteriorly from the gland with an infiltration of 27 mm, in the omental bag a meager amount of fluid, in the abdominal cavity effusion.

2nd day: catheterization of the celiac trunk for continuous infusion of a complex of drugs - emoxipin, lidocaine, cephalosporin, diavitol.

4th day: the catheter from the celiac trunk is removed.

Objectively: the state of moderate severity, dyspnea at rest 20 ', vesicular breathing, abdomen moderately swollen, slightly painful in the epigastrium, where the infiltration is palpated. HELL 170/100, heart rate 76, temperature 36.6 ° C. Peritoneal symptoms are not.

7th day: Ultrasound examination of abdominal organs: there is no effusion in the abdominal cavity. Pancreas 33-27-22 mm, a cyst forms in the body. In the stuffing bag infiltrate 20 mm.

27th day: in blood tests: НЬ 135 g / l, erythrocytes 4.1, leukocytes 6.5, stab 5%; bilirubin 12.3, urea 5.0, total protein 76 g / l, glucose 4.9, potassium 5.0 mEq / l, ALT 25, AST 31.

The patient was discharged without complications for 33 days.

Example 2

Patient M., born in 1980, was admitted to the surgical hepatology department of the 9th Minsk city clinical hospital with a diagnosis of acute pancreatitis.

Clinical diagnosis: acute necrotizing pancreatitis. Omentobursit. Paracolite on the right and left. Mesocolitis Pleurisy on the left.

2nd day: transferred to the intensive care and resuscitation department.

Objectively: the state is grave. Dyspnea at rest 24 '. Complaints of weakness, encircling pain at the top of the abdomen. Vesicular breathing. The abdomen is swollen, painful in the epigastrium. Blood pressure is not determined, the pulse 124 ', the temperature of 36.7 ° C.

In general, a blood test: НЬ 147 g / l, Ηΐ 46 mm, leukocytes 19.3, band 70%.

In the biochemical analysis of blood: bilirubin 13 μmol / l, urea 6.0, ALT 54, AST 48, calcium ionized 0.9, amylase 507 U.

The partial pressure of oxygen in capillary blood is 37 mm Hg, the buffer bases are 11 mmol / l deficient.

The prognostic score of gravity on Jaapzop = 7.

Ultrasound of the abdominal organs: liver + 3.4 cm, portal vein 10 mm, choledoch 4 mm, gallbladder 81x22 mm; pancreas 69 - 32 - 36 mm. In the body there is necrosis 61x20 mm, infiltration anteriorly 28 mm, posterior 22 mm, in the omental bag 150 ml of fluid.

In the paracolon on the right, the liquid balloon to the anterior surface of the awn is 32 mm thick, the wall of the intestine is intact. In the paracolon on the left is a liquid strip with a thickness of 8 mm. In mesocolon infiltrate 20x15 cm, with areas of loosening and compaction. In the left pleural cavity fluid.

The complex of therapy includes biospecific hemosorption on Ovosorb sorbent.

Day 4: Catheterization of the superior mesenteric artery for continuous infusion of a complex of drugs - emoxipin, lidocaine, cephalosporin, pentoxifylline.

10th day: the catheter is removed from the superior mesenteric artery.

Objectively: the state of moderate severity, dyspnea at rest 20 ', vesicular breathing, abdomen moderately swollen, slightly painful in the epigastrium, where the infiltration is palpated. HELL 120/80 mm Hg, pulse 84, temperature 35.8 ° C. Peritoneal symptoms are not.

- 6 007473

Day 17: Blood tests: HB 97 g / l, erythrocytes 3.0, leukocytes 8.0, stab cells 13%; bilirubin 16, urea 4.6, total protein 65 g / l, glucose 3.0, potassium 4.4 meq / l, ALT 62, AST 72.

Day 25: Ultrasound examination of abdominal organs. There is no abdominal effusion. Paracolite right and left no. Infiltration in the omental bag decreased, the liquid component increased.

The patient was discharged without complications for 33 days.

Example 3

Patient 3., born in 1958, was admitted to the pulmonary department of the 9th Minsk city clinical hospital with a diagnosis of acute post-traumatic right-sided pneumonia.

Clinical diagnosis: acute necrotizing pancreatitis. Parapancreatitis. Parakolit left. Left-sided lower lobe pneumonia. Pleurisy on the left. Intoxication delirium.

Objectively: the state is grave. Dyspnea at rest 36 '. Complaints of poor health, shortness of breath, back pain. Vesicular breathing. The abdomen is not swollen, painful in the epigastrium. HELL = 160/90 mm Hg, pulse 100 ', temperature 39.5 ° C.

In general, a blood test: НЬ 152 g / l, erythrocytes 3.68, leukocytes 7.2, stapled 14%, segmented nucleus 77%, lymphocytes 6%, monocytes 3.

In the biochemical analysis of blood: bilirubin 65 μmol / l, urea 6.4, total protein 57 g / l, glucose 12.1 mmol / l, ALT 148, AST 220, sodium 141, potassium 3.8, calcium ionized 0.96 chlorides 102.

Waikoi prognostic score = 6.

Day 2: Ultrasound examination of abdominal organs: the liver is enlarged, homogeneous, echogenicity (+ + +), the biliary tract is normal. The pancreas is not visualized. Spleen without features. The kidney contour is blurred; stones in the right kidney lumbar system are up to 5-6 mm.

Diagnostic laparoscopy. Conclusion: pancreatic necrosis, fatty hepatosis, intestinal paresis.

Transferred to the intensive care and resuscitation department, where the complex of infusion therapy includes lidocaine, emoxipin, pentoxifylline, antibiotics, biospecific hemosorption on Ovosorb sorbent.

9th day: chest X-ray, conclusion - left-sided n / lobar pneumonia.

10th day: control ultrasound: liquid accumulation of 130x27 mm along the left side canal. The wall of the adjacent descending colon is not changed. In the left pleural cavity fluid.

17th day: aspirated debridement of the paracolite on the left, fluid taken to study the presence of microflora. Answer for 23 days: no growth.

22nd day: objectively: the state is satisfactory, there is no dyspnea at rest, vesicular breathing, the stomach is not swollen, soft, painless, there are no data for paracolith.

HELL 120/80, pulse 80, temperature 36.6 ° C. Peritoneal symptoms are not.

In blood tests: Hb 88 g / l, erythrocytes 2.6, leukocytes 6.2, stab 8%; bilirubin 12, urea 4.6, total protein 66 g / l, glucose 7.0, potassium 4.3 mEq / l, ALT 48, AST 59.

The patient was discharged without complications on the 28th day.

Example 4

Patient K., born in 1939, was admitted to the Department of Surgical Hepatology of the 9th Minsk City Clinical Hospital with a diagnosis of acute pancreatitis.

Clinical diagnosis: acute biliary necrotizing pancreatitis. Parapancreatitis. Enzymatic peritonitis. Chronic calculous cholecystitis.

Objectively: the state of moderate severity. Complaints of pain in the epigastrium and right hypochondrium. Vesicular breathing. The abdomen is not swollen, painful in the right hypochondrium. HELL = 130/80 mm Hg, pulse 88 ', temperature 37.0 ° C.

In general, a blood test: Hb 138 g / l, erythrocytes 3.78, leukocytes 13, stacked 18%, segmented nucleus 62%, lymphocytes 16%, monocytes 4%.

In the biochemical analysis of blood: bilirubin 20.5 μmol / l, urea 11.4, total protein 47 g / l, glucose 6 mmol / l, ALT 106, AST 110, sodium 137, potassium 3.9, calcium ionized 0.93 , chlorides 110.

Vapkoi prognostic score = 6.

Day 2: Ultrasound examination of abdominal organs: the liver is homogeneous, the gallbladder is 80x40 mm, there are many small stones in the lumen. Pancreas 28-14-27 mm, echo (+ +).

3rd day: laparotomy. Cholecystectomy. Drainage of the abdominal cavity and omentum bag.

4th day: catheterization of the celiac trunk for continuous infusion of a complex of drugs - emoxipin, lidocaine, thienam, pentoxifylline.

6th day: biospecific hemosorption on Ovosorb sorbent is included in the therapy complex. Radiography of the abdominal cavity. Conclusion: bilateral hydrothorax.

8th day: the catheter is removed from the celiac trunk.

Day 20: in blood tests: НЬ 109 g / l, erythrocytes 3.5, leukocytes 5.2, stab 5%; bilirubin 14, urea 3.1, total protein 70 g / l, glucose 6.5, potassium 4.9 meq / l, ALT 14, AST 19.

- 7 007473

23rd day: objectively: the state is satisfactory, there is no shortness of breath, vesicular breathing, the abdomen is not swollen, it is not very painful in the epigastrium. HELL 120/80, heart rate 76, temperature 36.6 ° C. Peritoneal symptoms are not.

The patient was discharged without complications on the 24th day.

Example 5

Patient V., born in 1951, was admitted to the Department of Surgical Hepatology of the 9th City Clinical Hospital with a diagnosis of acute pancreatitis.

Clinical diagnosis: acute necrotizing pancreatitis. Omentobursit. Paracolite on the right and left. Mesocolitis Pleurisy on the left.

On the day of admission (1st day): transferred to the intensive care unit and reanimation.

Objectively: the state is grave. Dyspnea at rest 24 '. Complaints of weakness, encircling pain at the top of the abdomen. Vesicular breathing. The abdomen is swollen, painful in the epigastrium. Blood pressure is not determined, the pulse 124 ', the temperature of 36.1 ° C.

In general, a blood test: НЬ 148 g / l, Н1 46 mm, leukocytes 19.4, stabbed 67%.

In the biochemical analysis of blood: bilirubin 33 μmol / l, urea 7.1, ALT 54, AST 48, calcium ionized 0.9, amylase 902 ED.

Oxygen partial pressure in capillary blood 34 mm Hg, buffer bases deficiency

II mmol / l.

The prognostic score of gravity in Wakop = 7.

Ultrasound examination of abdominal organs: liver + 3.4 cm, portal vein 11 mm, choledoch 4 mm, gallbladder 82x26mm, pancreas 61 - 34 - 39. 37x21 mm in body necrosis, anterior infiltration 27 mm, posterior 21 mm, in omentum bag of 250 ml of liquid.

In the paracolon on the right, the liquid balloon to the anterior surface of the awn 30 mm thick, the intestinal wall is intact. In the left paracolon liquid strip thickness of 6 mm. In mesocolon infiltrate 182x153 mm, with areas of loosening and compaction. In the left pleural cavity fluid.

Catheterization of the celiac trunk for continuous infusion of sequentially cytoprotective complex I (solutions of III or IV generation cephalosporin, emoxipin as an antioxidant and as an antiphospholipase preparation, diavitol, pentoxifylline) and III (cephalosporin solutions

III or IV generation, emoxipin as an antioxidant and as an antiphospholipase preparation, diavitol as an antihypoxant and as a drug regulating metabolic processes of cells, pentoxifylline).

2nd day: biospecific hemosorption on Ovosorbe sorbent is included in the therapy complex.

7th day: the catheter is removed from the celiac trunk.

Objectively: the state of moderate severity, dyspnea at rest 20 ', vesicular breathing, abdomen moderately swollen, slightly painful in the epigastrium, where the infiltration is palpated. HELL 120/80 mm Hg, pulse 84, temperature 36.8 ° C. Peritoneal symptoms are not.

Day 13: in blood tests: HB 97 g / l, erythrocytes 3.0, leukocytes 8.0, staple 13%; bilirubin 16, urea 4.6, total protein 65 g / l, glucose 3.0, potassium 4.4 meq / l, ALT 62, AST 72.

Day 18: Ultrasound examination of abdominal organs. There is no abdominal effusion. Paracolite right and left no. Infiltration in the omental bag decreased, and the liquid component decreased.

The patient was discharged without complications on the 30th day

Thus, the results show the effectiveness of medical treatment of pancreatitis and prevention of complications of acute necrotizing pancreatitis in accordance with the claimed method, including the effectiveness of the impact on the barrier function of the intestine for the prevention of septic complications of acute pancreatitis.

Literature.

1. Nepgu W.L. BG \\ ъ.Μ.Ό., Pa1s1dN V. Kep! III, Μ.Ό. Asi1e Rapstea! Yk: Mapadetep! og ssrBsaIpd πGesyop. Tke Ashepsap Guide, 2000, 66: 145-152.2. Kgateg KM, Leuu N. Rtorkuyasis apyyuysk Gogueuyuet asi! Erapstey! To:! Kek Led1spshpod oG anga. Rkagtaso! Kagaru.1999; 19: 592-602.

3. 8yashu V., Ketrrashep E., Riolakkashep R., e! A1 .: Eag1u apyYoys! Gea! Tep! sh asi! e pesgoBhtd rapsteyyk. Fuck 1995; 346: 663-667.

4. \ Walecke1. Apy a11 .: IAR Syjekpek Gog! Ke 8iks1sa1 Mapadetep! og Asi! e RapsgeaShk. Rapsgeal 2002; 2: 565-573

5. Yieep E.E.T., Nor HU.ST. Lapde Ι.Ε., W.Sh.N. Sop! GoShey Skshsa1! P1 oG kolesuye yesop! Atssayop Gogh! Kea gea! Tep! oh keuet asi! e rapsteyyk. App 8gd 1995; 222: 57-65.

6. K. Takeya, I. Uataisy, K. 8k1Biua, M. 8patita, Υ. M1kat1, 8. Ma! Kipo. Weepy Sippioik Vegüp1 Ag1eg1a1 Shikyup og Progamee [Pyyogi Apy ApoYoisch! Mapadetep! OG Asi! e Jesgok / td Rapstayyk. Rapsgea! 2001; 1: 668-673.

7. It goes to the train; M.W. Mac; Mekte! Υππγ; KtaP Biek; N. Ike! Poppy; Nkp Kosaa1kap. Repe! Ha! Ju og Megorepet apy Segorkp sh! O Rapsteis Tkkie Sketch! Soigke oG Ehreptep! A1 Asi! E RapsgeaShk. Rapsgeac. 2002; 24: 264-268

- 8 007473

8. Tkotak 1. But \ tagy. MB. Basy. Mskaye1 V. Tetr1e, MB. Ргорку1аскс Apikuksk Liegeg 1N with you! Ogopood oG 1GesTsi ny sgok1k 8η 8euege Asi! E Rapsgeyjk. ί At So11 Sigd. Wo1. 195. Νο. 6. Beseter 2002. p759767.

9. Ссаса1ке. B .. Zakag A .; Zyen R.; How! EShsh. WITH.; Ziobp V .; God N .; Wha K. Asi! E rapsgeayik apy bac! Epa1! Gapkosos! Jupe. B1Deck! Gee Bieakek apj Zaepsek. ν. 46. Bkie 5. p.1127-1132.

10. The first K. K. W ectt. Rkb. AKYR. Bopp teloag. Rkb. ΑΚΝΡ. apy Nahsu A11ep. ΑΚΝΡ. Si! BookGypsyop ίη Cr111sa11u III Rayep! To: A Ketlee \\ · og! Ke Bkegakie. Atepsap 1oita1 oG Spisa1 Saga. May 1997 ^ o1. 6. No. 3. p. 204-209.

11. Vak11 1. Atta. Kole og! Ke sy! r 1Be Co-ogk oG Ze'e ege Asi! e Rapsgeayik. Rapsgeac 2003; 26 (2): 122,129.

12. Kosyog MA. Kosyog N .. Si1au Ζ .. Sokse O. Tke eGGess! To og rep! Okhuy11she op bas! Épa1 1gapk1osayop ayeg t! Ek! Ta1 ok! Ryosyop. Zkosk. 2002 Hades 18: 148-51.

13. 8 Midekakdek1; З1шр наД. Sheg [ptggu t Asi! E Rapsgeayik apy M1ydayayop byi Supipioik Ag! Epa1 ItGikyup oG an Apyylois νίη! 1e Zirepog Mekep! Ops Ag! Egu. Rapsgeac 2001; 23: 204-211

14. Zakya ^ a! N. Kaktap apy a11 .: 1p! Ekyp1 NuroregGpkyup Sop! Py! Ek! O Xi! Vateg Bayige sh 8e \ 'ege Asi! E Rapsgeayyk. 1oita1 og Sak! Gosh! Ek! Ta1 Zigdeg. №1. 7. No. 1.2003.

15. E.S. Slc. 8.B. Ra! E1. R.K. Skye \\ '1sk. S. ^ agygk !. A. Siggu. S.B. Sag1cop. S1i! Atshe yergBakop GassH! A! Ek! Itoig pesgokB Gus! Og tyyisy byas! Épa1! Si! 2003; 52: 224-230.

16. T. ΙζίΚοιΙζίΚ S1i! Atshe ktayk / ek t! Ek! Ta1 regteyyu apy gayisek rapsgeays shGeskop asi! E ehreptep! A1 rapsgeayyk 1 Sak! Gots! Ek! Sigd 1997 grades; 1 (1): 40-47.

17. V. 1. Atta; R. Vichdegai; R. Na \ gkeu; M.1. MSMOP Tack Ea1u 1psgeake t 1p! Ek! Ta1 Regteyuyu apy Zuk! Et1s Epoy! Ohsh Ehrokige t Rayep! K \ νί11ι See Ee Asi! E Rapsgeyyk 1k №! Akkoa! Her \\ 'kk Zook! Et1s you! Epa1 Tgap1osayop: Molesiig [pteydakop oG M1sgo1-11 βΛ w! 1e Vloi. Rapsgeac 2003; 26 (1): 18-22.

Claims (12)

CLAIM 1. A method for the treatment of pancreatitis by catheterization of the celiac trunk and continuous regional arterial infusion of a complex of drug solutions based on an antibiotic and an antienzyme preparation. characterized in that. that at least one cytoprotective complex is administered as a complex of drug solutions. composed of at least one broad-spectrum antibiotic. at least one antioxidant. at least one anticytokine drug. at least one antihypoxant and as an antiferment preparation of at least one antiphospholipase preparation. while the complex is administered continuously for 5-7 days. 2. A method for the prevention of septic complications of acute necrotizing pancreatitis by catheterization of the superior mesenteric artery and continuous regional arterial infusion of a complex of drug solutions based on an antibiotic and an antienzyme preparation. characterized in that. that at least one cytoprotective complex is administered as a complex of drug solutions. composed of at least one broad-spectrum antibiotic. at least one antioxidant. at least one anticytokine drug. at least one antihypoxant and as an antiferment preparation of at least one antiphospholipase preparation. while the complex is administered continuously for 5-7 days. 3. The method according to any one of claims 1 or 2. characterized in that. that cytoprotective complex I. is introduced as a cytoprotective complex. in which a III or IV generation cephalosporin solution is chosen as an antibiotic. as an antioxidant choose a solution of emoxipin. as an antihypoxant, a solution of diavitol is chosen. pentoxifylline is chosen as the anticytokine drug. as an antiphospholipase preparation, a solution of emoxipin is chosen. 4. The method according to any one of claims 1 or 2. characterized in that. that the cytoprotective complex II is introduced as a cytoprotective complex. in which a third or fourth generation cephalosporin solution is selected as an antibiotic. as an antioxidant choose a solution of emoxipin. as an antihypoxant, a solution of diavitol is chosen. pentoxifylline is chosen as the anticytokine drug. as an antiphospholipase drug, lidocaine is chosen. 5. The method according to any one of claims 1 or 2. characterized in that. that a cytoprotective complex III is introduced as a cytoprotective complex based on cytoprotective complex I and at least one drug. regulating the metabolic processes of cells. 6. The method according to any one of claims 1 or 2. characterized in that. that as a cytoprotective complex, a cytoprotective complex IV is introduced based on the cytoprotective complex II and at least one drug. regulating the metabolic processes of cells. 7. The method according to one of claims 5 or 6. characterized in that. that as a drug. regulating the metabolic processes of cells. Diavitol is administered. - 9 007473 8. The method according to any one of claims 1 to 7, characterized in that at least two different cytoprotective complexes I, II, III and IV are sequentially administered as a complex of drug solutions. 9. The method according to any one of claims 1 to 8, characterized in that diavitol-gel is additionally administered by probe. 10. The method according to any one of claims 1 to 8, characterized in that an omegatriene is additionally administered by probe. 11. The method according to any one of claims 1 to 8, characterized in that diavitol gel and omegatriene are administered via the probe. 12. The method according to any one of paragraphs. 1-11, characterized in that they additionally carry out hemosorption on Ovosorb.