RU2291708C2 - Agent for treatment and prophylaxis of acute pancreatitis and methods for its using - Google Patents

Abstract

FIELD: medicine, surgery.

SUBSTANCE: invention relates to treatment and prophylaxis of acute pancreatitis in humans and agent used for this aim. Agent represents serum against true viper venom. Method involves preliminary administration in a patient of anti-histamine preparation and in 30 min serum is administrated. Serum is diluted with physiological solution and administrated by intravenous route by drops being firstly in dose 0.1 ml, then in 10 min in dose 0.25 ml, and then in 15 min - the remainder dose. In treatment of acute pancreatitis method involves administration of serum in dose 450 AE diluted in 300 ml of physiological solution in the first day, 300 AE of serum diluted in 200 ml of physiological solution in the second day and 150 AE of serum diluted in 100 ml of physiological solution in the third day. Prophylaxis of acute pancreatitis in humans is carried out by administration of 150 AE of seum diluted in 100 ml of physiological solution. Invention provides inhibition of enzymatic activity of pancreas that enhances effectiveness of treatment in case of severe forms of pancreatitis in edema and necrosis stage also, and promotes to prophylaxis of acute pancreatitis after direct surgery operations on pancreas and carrying out endoscopy in cholangiopancreatography procedure.

EFFECT: enhanced effectiveness of treatment and prophylaxis, valuable medicinal properties of agent.

3 cl, 4 ex

Description

The invention relates to medicine, namely to surgery, and can be used for the treatment and prevention of acute pancreatitis.

A known method of treating acute pancreatitis using 5-fluorouracil. The method consists in the intravenous administration of 5-fluorouracil at a dose of 3-5 mg / kg of the patient’s body weight after 4 hours for 2-3 days and is aimed at inhibiting the synthesis of pancreatic enzymes and suppressing inflammatory mediators (Laptev V.V. and Pivazin G.A. Cytostatics in the treatment of acute postoperative pancreatitis. - "Surgery", 1988, No. 9, S. 144-145).

The disadvantage of this method is the toxicity of 5-fluorouracil, the manifestations of which include changes in the protein spectrum of blood serum and potassium ions in red blood cells, inhibition of erythrocyte and neutrophilic bone marrow growth, degenerative changes in the small intestine mucosa with subsequent dyspeptic disorders and a decrease in the secretory acid-forming function of the stomach.

The closest known method is the use of octreotide (sandostatin) for the treatment and prevention of acute pancreatitis. Octreotide is a derivative of the natural hormone somatostatin, but has a more powerful and long-lasting (up to 8-12 hours) action. Available in ampoules and vials for subcutaneous and intravenous administration. Octreotide in a daily dose of 300-600 μg suppresses exocrine pancreatic function, having an inhibitory cytoprotective effect, inhibits the synthesis of enzymes, vasoactive peptides and amines. Octreotide is administered intravenously at a dose of 100-200 mcg 3 times a day. The criterion for drug withdrawal is the normalization of amylase activity in the blood and / or urine and the transfer of the patient to enteral nutrition (Filimonov M.I., Gelfand B.R. et al. Experience with octreotide in destructive pancreatitis. Losev SV, Fedenko V. B. The use of octreotide for the prevention of pancreatitis during RCHP - “Experience in the clinical use of OCTREOTID”, collection of articles No. 2, Farm-Sintez CJSC. M., 2003, p.5-6, 12-13).

In addition to the existing advantages, the use of octreotide has the following disadvantages:

- octreotide does not have a significant effect on the indices of the blood inhibitory system: general antitryptic activity and level of alpha-2-macroglobulin. Under these conditions, alpha-2-macroglobulin associated with trypsin retains kininogenase activity, thereby reducing the effect of neutralization of active enzymes, therefore, blood circulation in the microvasculature does not improve, and this contributes to the progression of the pathological process;

- octreotide increases the tone and contractility of the sphincter of Oddi, resulting in a delay in pancreatic secretion in the duct system, which enhances hypertension syndrome and promotes the release of active enzymes into the pancreatic tissue and enhances autocatalytic processes;

- Octreotide is an expensive drug, which makes it inaccessible to the bulk of patients.

The task to which the invention is directed is to increase the effectiveness of treatment and reduce its cost.

The technical result from the use of the proposed solution is to suppress the enzymatic activity of the pancreas, due to which there is a relief of the pathological process and improvement of treatment results.

The specified technical result is achieved by the fact that for the treatment and prevention of acute pancreatitis use serum against the venom of the viper ordinary.

There is no information in the information sources about such use of serum.

The essence of the invention lies in the fact that in a method of treating acute pancreatitis, including drip intravenous administration of a drug, according to the invention, the patient is administered serum against venom of the viper ordinary on the first day in the amount of 450 AU, diluted in 300 ml of saline, on the second day in the amount of 300 AE diluted in 200 ml of saline and on the third day 150 AU, diluted in 100 ml of saline, and the introduction of serum is carried out in parts: first 0.1 ml, then after 10 minutes 0.25 ml of this drug, then after 15 minutes - about tal dose, at the same time every day for 30 minutes before the introduction of patient serum gives an antihistamine. The technical result is also achieved by the fact that in the method for the prevention of acute pancreatitis, including drip intravenous administration of the drug, according to the invention, the patient is administered serum against the venom of the viper ordinary in the amount of 150 AU, diluted in 100 ml of saline, and the introduction of serum is carried out in parts: first 0.1 ml, then after 10 minutes 0.25 ml of this drug, then after 15 minutes - the rest of the dose, while 30 minutes before the introduction of serum, the patient is given an antihistamine.

The rationale for the possible use of serum against the venom of the viper vulgaris was the similarity in the content of hemolytic and proteolytic enzymes in the venom of snakes (such as the viper vulgaris) and in the pancreas of man. The clinic for acute pancreatitis, manifested by severe toxemia and hemodynamic disorders, also largely resembles a clinic for snake venom poisoning. Experimental studies have confirmed these data, and the use of serum against the venom of the viper ordinary has been effective. All this taken together predetermined the use of serum in the treatment of severe forms of pancreatitis (both in the stage of edema and in the stage of necrosis). The serum is commercially available and is a protein fraction of the blood serum of horses containing specific immunoglobulins that is hyperimmunized with venom of the ordinary viper, purified and concentrated by peptic digestion and salt fractionation (“INSTRUCTIONS on the use of serum against the venom of the ordinary viper horse purified concentrated liquid”).

A method of treating acute pancreatitis is as follows. After a diagnosis of acute pancreatitis is established by a patient with all modern methods, including laparoscopy (examination of the abdominal cavity using a video endoscope), the existing abdominal effusion (which accompanies this disease) is eliminated and drainage tubes are brought into the free abdominal cavity. According to the instructions, previously (in 30 minutes), the patient is given prednisone or any other antihistamine (dimidrol, pipolfen) in order to reduce the risk of anaphylactic shock on the introduction of serum. On the first day, serum is added against venom of the viper ordinary in the amount of 450 AU diluted in 300 ml of saline, on the second day in the amount of 300 AU diluted in 200 ml of saline, and on the third day, 150 AU diluted in 100 ml of saline, with the introduction of serum carried out in parts: first 0.1 ml, then after 10 minutes 0.25 ml of this drug, then after 15 minutes - the rest of the dose. Patients after treatment note an improvement in their general condition: first of all, the pain syndrome stops, vomiting stops, intestinal paresis decreases, blood counts normalize.

Example 1. Patient T., 42 years old, medical history 14463, was admitted to the clinic 02.08.03 1 hour after the illness after drinking plenty of alcohol with complaints of pain in the upper abdomen of considerable strength and intensity of herpes zoster, numerous vomiting, not giving relief. The pains progressively intensified, and the patient was forced to call an ambulance. The patient's condition is serious, the color of the skin is pale. During the examination, there was twice vomiting of abundant gastric contents without signs of blood. Moderate shortness of breath up to 22 breaths per minute. Pulse up to 98-100 beats per minute, blood pressure 100 to 60 mm Hg The abdomen is moderately swollen, palpation sharply painful. Preliminary diagnosis: the patient has a picture of peritonitis, a shock of 1-2 degrees, most likely due to pancreatic necrosis. After a 2-hour detoxification therapy and blockade of the round ligament with a solution of novocaine 1/4% 250 ml, a consultation was held. Taking into account the obtained analyzes: amylase activity 1090 g / l · h at a rate of 220 g / l · h, blood test - leukocytosis with a shift of the rods to 28, it was decided to perform diagnostic laparoscopy. Laparoscopy results: up to 2500 ml of hemorrhagic fluid in the abdominal cavity, no fatty plaques, retroperitoneal tissue infiltrated with serous-hemorrhagic fluid. The pancreas is enlarged in size throughout the dark cherry color with patches of necrosis. Three drains have been brought into the small stuffing bag, into the subhepatic space and into the small basin. Conclusion: hemorrhagic pancreatic necrosis, enzymatic hemorrhagic peritonitis, aseptic enzymatic cellulitis of retroperitoneal fiber. In this regard, it was decided to carry out specific treatment with serum against the venom of the viper ordinary. 30 minutes before the administration of serum, the patient was given an injection of dimidrol subcutaneously in an amount of 2 ml. after which specific therapy with anti-snake serum against venom of the viper ordinary at a dose of 450 AU (three ampoules), diluted in 300 ml of saline intravenously, dropwise: first 0.1 ml, after 10 minutes 0.25 ml and after 15 minutes the rest of the serum dose . There was no reaction to the administration of serum. The patient noted a decrease in pain and fell asleep. Within 2 hours, a decrease in paresis was observed. The abdomen gradually became less swollen during 10-12 hours, soft on palpation, the symptoms of peritoneal irritation ceased to be detected. A sharp decrease in the amount of effusion was noted compared with the course of the postoperative period in patients using sandostatin. On the second day, the patient was administered 300 AE (two ampoules) of serum diluted in 200 ml of saline with prior administration of prednisolone at a dose of 60 mg. Serum was administered in portions as described above. On the third day, 150 AE (one ampoule) of serum was administered, taking all precautions against complications of serum administration indicated above.

The patient's condition gradually progressively improved and on the 29th day the patient was discharged in satisfactory condition.

Example 2. Patient V., 69 years old, medical history 786. A patient 2 years ago had a planned cholecystectomy for cholelithiasis using the laparoscopic method. Was admitted to the hospital with complaints of periodic pain in the right hypochondrium, especially after eating fatty foods. Given the history of gallstone disease (the presence of small calculi), narrowing of the terminal portion of the common bile duct was not ruled out. Pancreatography was performed, after which the patient developed a picture of acute pancreatitis. Complex treatment was carried out, including infusion therapy, antibacterial, antispastic, antienzyme (sandostatin 100 μg three times a day). The condition did not tend to improve. By the end of the third day, the patient in the epigastrium began to determine the infiltrate and the patient was transferred to the intensive care unit, where she underwent the entire complex of treatment aimed at stopping the pathological process. Despite the therapy, the patient's condition continued to worsen: body temperature increased to 38.7 degrees, blood leukocytosis increased with a shift of the stab core, parapancreatic infiltrate increased in size, after the consultation, the patient decided to operate. 12/09/03, under general anesthesia, a median laparotomy was performed, followed by an audit of the pancreas and abdominal organs. The abdominal cavity was drained through separate incisions, and sutures were placed on the median postoperative wound. Postoperative diagnosis: total infected mixed pancreatic necrosis, parapancreatic infiltrate, forming subhepatic abscess, local serous-purulent peritonitis. Given the unfavorable course and lack of effect of conservative therapy, including sandostatin, it was decided to conduct treatment with serum against viper venom as usual. On the first day, 30 minutes after the administration of the antihistamine, 450 AE (three ampoules) was administered, on the second day - 300 AE (two ampoules), on the third day - 150 AE (one ampoule). The condition began to improve progressively and on day 9 the patient was transferred from the intensive care unit to the general ward. Gradually, the necrotic tissues (sequestration and detritus) left, and the patient in satisfactory condition was discharged home on day 39. In this case, we are again convinced that sandostatin is not always effective, even with its early use. Thus, the effectiveness of a specific serum against the venom of an ordinary viper, which is used not only in the stage of enzymatic toxemia (the first period of the development of the disease), but also in the second period of the development of the disease (in conditions of infected pancreatic necrosis) is visible.

Prevention of the development of acute pancreatitis is necessary after direct operations on the pancreas and during endoscopic retrograde cholangiopancreatography (ERCP). The possibility of developing pancreatitis is explained by a trauma to the duct system due to increased pressure during injection of a contrast medium, as well as high osmolarity of radiopaque substances.

A method for the prevention of acute pancreatitis is as follows.

The patient is given an antihistamine drug and after 30 minutes they begin to administer serum against the venom of the viper ordinary in the amount of 150 AU, diluted in 100 ml of saline. The introduction of serum is carried out in parts: first 0.1 ml, then after 10 minutes 0.25 ml of this drug, then after 15 minutes the rest of the dose.

The need for the use of serum in order to prevent acute pancreatitis during ERCP can be clarified by the following example.

Example 3. Patient Ch., 57 years old, medical history 838, diagnosed with a malignant tumor of the retroduodenal part of the common bile duct, was admitted to the hospital on 10.10.04 for ERCP to clarify the diagnosis and possible surgical treatment. Given the presence of a tumor in the common bile duct, the likelihood of developing acute pancreatitis after this study (the introduction of contrast under pressure into the common bile duct and pancreatic duct) is very high. In order to prevent acute pancreatitis, it was decided to use a specific serum against the venom of the common viper. To this end, 2 hours before the study, 150 AE serums were introduced intravenously, diluted in 100 ml of saline: at the beginning of 0.1 ml of the substance, after 10 minutes 0.25 ml of this drug, then after 15 minutes the rest of the dose. To prevent any reactions to serum 30 minutes before its administration, an injection of diphenhydramine in an amount of 2 ml was made. 2 hours after the introduction of serum in this way was performed ERCP contrast "Omnipack". Despite the fact that there was a tumor of the terminal portion of the common bile duct and increased pressure was created in the pancreatic duct with ERCP, nevertheless, with the use of serum, this did not lead to the development of acute pancreatitis. The patient felt quite satisfactory, no pain syndrome was detected, there was no increase in pancreatic enzymes, as one of the main signs of acute pancreatitis.

Example 4. Patient A., 70 years old, medical history No. 8, was admitted to the clinic on 4.01.2005 with a diagnosis of malignant tumor of Vater papilla, obstructive jaundice with complaints of general weakness, loss of appetite, skin itching, jaundice. From the anamnesis it was found that in July 2004, an increase in body temperature up to 38 g was noted. and itchy skin. These symptoms were observed for a short time and the patient did not attach any particular importance to this, and did not consult a doctor. I felt worse from December, when my body temperature rose again to 39 gr., Itchy skin appeared and jaundice began to grow progressively. The studies of FGS and spiral computed tomography made it possible to determine the tumor of the ampullar section of the common bile duct with the transition to the Vater's nipple region. A biopsy of Vater's nipple confirmed the diagnosis. It was decided to carry out a radical operation pancreatoduodenal resection. In order to prevent postoperative pancreatitis, an hour before the operation, the patient was injected with subcutaneous injection of dimidrol in the amount of 2 ml, after which, after 30 minutes, a specific anti-snake serum was injected dropwise against the venom of the ordinary viper - initially 0.1 ml, after 10 minutes 0.25 ml, after 15 minutes - the remaining dose in the amount of 150 AU. There was no reaction to the administration of serum. The operation was performed on January 12, 2005. The postoperative period was uneventful, an increase in amylase activity (the main sign of pancreatitis) was not observed, and there was no pain. The patient in satisfactory condition was discharged on January 31, 2005.

Such a preventive measure was taken in 31 patients and in no case was there any development of signs of acute pancreatitis. Thus, the use of serum against viper venom is an effective means of preventing acute pancreatitis during operations on the pancreas and endoscopic retrograde pancreatocholangiography.

Claims (3)

1. The use of serum against venom of the viper ordinary as a means for the prevention of acute pancreatitis in humans or the treatment of acute pancreatitis in humans, except for pancreatitis caused by venom of the viper. 2. A method for the treatment of acute pancreatitis in humans, in addition to venom viper ordinary, including drip intravenous administration of a drug, characterized in that serum is administered against venom viper ordinary on the first day in an amount of 450 AU diluted in 300 ml of saline, on the second day in 300 AE diluted in 200 ml of saline, and on the third day, 150 AE diluted in 100 ml of saline, and the introduction of serum is carried out in parts: first 0.1 ml, then after 10 minutes 0.25 ml of this drug, then after 15 minutes the rest dose, and every day 30 minutes before the introduction of serum, the patient is given an antihistamine. 3. A method for the prevention of acute pancreatitis in humans, including drip intravenous administration of a drug, characterized in that the serum is administered against the venom of the ordinary viper in the amount of 150 AU diluted in 100 ml of saline, and the introduction of serum is carried out in parts: first 0.1 ml, then after 10 minutes, 0.25 ml of this drug, then after 15 minutes the rest of the dose, and 30 minutes before the administration of serum, the patient is given an antihistamine.