RU2245718C2 - Method for pharmacological correction of endogenous intoxication in case of acute destructive pancreatitis - Google Patents

Abstract

FIELD: medicine, surgery.

SUBSTANCE: at the background of basic therapy in complex therapy of acute pancreatitis one should introduce ceruloplasmin to be applied at the dosage of 600-1000 mg/d for 5 d. If necessary, the course of ceruloplasmin introduction should be repeated. This method provides pancreatic tissues viability in case of pancreonecrosis by increasing efficiency of correction the endogenous intoxication and decreasing the number of complications in the course of therapy conducted.

EFFECT: higher efficiency of pharmacological correction.

3 ex

Description

The invention relates to medicine, in particular to surgery, and can be used to treat acute destructive pancreatitis.

Acute destructive pancreatitis takes 3rd place among acute diseases of the abdominal organs. Its course is characterized by a high frequency of complications leading to death. In 75% of cases, severe endotoxemia is noted, leading to the development of multiple organ failure syndrome, which determines the urgency of choosing the method of treatment (correction) of endotoxemia in patients with this pathology.

A known method of treatment of acute destructive pancreatitis, based on basic therapy:

- nasogastric drainage;

- local hypothermia;

- analgesia;

- the appointment of antispasmodics;

- infusion therapy in the regime of forced diuresis.

In severe cases, basic therapy is added:

- course administration of pancreatotropic drugs (octreatide, ribonuclease, cytostatics);

- antienzyme preparations (kontrikal, gordoks);

- rational antibacterial therapy (third generation cephalosporins, fluoroquinolines, carbapenems and metrogil);

- methods of extracorporeal detoxification (plasmapheresis, hemosorption, indirect electrochemical oxidation of blood (NPECHO));

- Surgery of a closed or open type.

There is no one method and drug effective in the treatment of acute destructive pancreatitis. During treatment, a choice and combination of means and methods of treatment are carried out depending on the severity of the course of the disease (Kostyuchenko A.L., Gurevich K.Ya., Lytkin M.I. “Intensive care of postoperative complications - a guide for doctors”, St. Petersburg, Ed. SpetsLit, 2000, p. 340-363).

The applied treatment regimens for destructive pancreatitis do not take into account the need for exposure to severe hypoxic-ischemia of the pancreas and the main organs and systems of detoxification and the occurring “oxidative stress”. Therefore, at present, among pancreatotropic drugs, drugs with antihypoxic and antioxidant properties come to the fore. The study of the possibility and assessment of the role of antihypoxic and antioxidant therapy in the complex treatment of destructive pancreatitis in order to increase the stability of ischemic organs and tissues during necrobiosis is relevant.

Closest to the proposed invention in technical essence and the achieved result is a method of treating destructive pancreatitis with complicated course, when the complex of basic therapy includes oral administration of the drug "Olifen" in a dose of 1.5-2 g / day for 10-21 days. The resorptive effect of Olifen includes the following effects:

- antihypoxic (release of the respiratory chain at the level of cytochrome C);

- antioxidant (inhibition of lipid peroxidation (LPO));

- immunomodulatory (improvement of the processes of cellular respiration of lymphocytes);

- hemocirculation (restoration of the zeta potential of red blood cells and other membrane effects that normalize the processes of vascular permeability and adhesion of formed elements);

- adaptogenic and trophic (increasing the energy potential of cells).

"Oliphene" blocks LPO processes, protecting cell membranes from destruction, and also improves microcirculation around foci of necrosis, enhancing tissue respiration and cell energy. Intensive therapy with the use of "Olifen" allows to achieve the resorption of small foci and the processes of melting and sequestration of large destruction zones under aseptic conditions (Vashetko R.V., Tolstoy A.D., Kurygin A.A., Stoyko Yu.M., Krasnogorov VB “Acute pancreatitis and pancreatic injuries: a guide for doctors”, St. Petersburg, publ. “Peter”, 2000, p.209-211).

The disadvantage of this method is the internal (non-parenteral) administration of the drug, which leads to a slow, delayed onset of the therapeutic effect and the inability to use it in the complicated course of pancreatic necrosis (the presence of toxic infectious delirium, ARF using artificial lung ventilation (ALV). In addition, the drug is synthetic compound (poly- (2,5-dihydroxyphenylene) -4-thiosulfate sodium.) With its use, the development of allergic reactions and hypotension, which makes it impossible zhnym its use in patients with necrotizing pancreatitis complicated by systemic organ failure with a predominance of AHF.

The problem solved by the invention is the expansion of the range of drugs used in the treatment of acute destructive pancreatitis.

The technical result from the use of the invention is to improve the quality of the course of pancreatic necrosis, expressed in reducing the degree of endogenous intoxication, as well as the exclusion of the development of allergic reactions due to the fact that the proposed drug is obtained from human blood and does not contain foreign components.

This result is achieved by the fact that against the background of the basic therapy in the complex treatment of acute destructive pancreatitis, ceruloplasmin is administered at a dose of 600-1000 mg / day for 5 days with possible repeated courses.

The method is as follows. Ceruloplasmin before administration is dissolved in 200 ml of physiological saline or 5% glucose and administered at a rate of 30 drops per minute according to the instructions for use of the drug. Ceruloplasmin is administered to the patient at a dose of 600-1000 mg / day for 5 days with possible repeated courses.

These conditions are optimal, since the drug in an amount of less than 600 mg does not have the desired therapeutic effect, and the excess of a single dose of the drug over 1000 mg is not described in the literature and possible side effects have not been studied.

Used ceruloplasmin is a protein secreted from human blood. This is the main blood antioxidant that binds superoxide radicals and prevents lipid peroxidation of cell membranes (Mashkovsky MD “Medicines”, Moscow, publishing house “Medicine”, 1993, v.2, p. 182-183).

The advantage of this method is that the drug is administered parenterally. Since ceruloplasmin is a human blood product, it does not cause allergic reactions, is well tolerated by patients, does not lead to the formation of phlebitis during administration. Being a natural antioxidant, ceruloplasmin enhances the body's defense against lipid peroxidation, stabilizes hemodynamics and does not cause a decrease in blood pressure at the time of infusion. The antihypoxic properties of ceruloplasmin are proven. The above advantages make it possible to use the drug in the treatment of patients with destructive pancreatitis complicated by systemic multiple organ failure (SPON) with the phenomena of acute respiratory failure (ARF) and acute heart failure (AHF).

Example 1. Extract from the medical history. Patient K., 70 years old, was undergoing treatment at MLPU City Hospital for Emergency Medicine in Nizhny Novgorod from 05.14.02 with a diagnosis of infected pancreatic necrosis; pancreatogenic abscess; parapancreatogenic, paracolytic phlegmon with abscess formation of retroperitoneal space. Spilled abacterial enzymatic peritonitis. External pancreatogenic fistula. On admission: blood α-amylase - 45.5 mg / ml, C-reactive protein - 120, total bilirubin - 26.4 μmol / l, total protein - 74.2 g / l, leukocyte intoxication index (LII) - 13 , 7, medium molecules - 0.6 units; prothrombin index - 41%, ESR - 10 mm / hour. The treatment: abactal - 800 mg / day, metrogil - 200 mg / day, octreatide - 0.3 mg / day, contracal - 100 thousand units / day, actovegin - 400 mg / day, 5-fluorouracil - 10 mg / day , pentoxifylline, fraksiparin, reopoliglukin, sibazon, diphenhydramine, ceruloplasmin - 600 mg / day in 200 ml of 0.9% sodium chloride intravenously for 5 days. By the 5th day of the therapy, there was a decrease in blood α-amylase to 9.4 mg / ml, C-reactive protein to 60, total bilirubin to 13.2 μmol / L, leukocyte intoxication index to 9.3, medium molecules to 0.3 units, total protein up to 59.5 g / l. At the same time, an increase in the prothrombin index was noted - 83%, ESR - 29 mm / hour. During the entire time of treatment, the patient underwent repeated operations (4 in total): bursoentoscopy, bursoscopy, drainage of the omental bursa, sequestrectomy. The patient was treated for 10 days at the intensive care unit. The total bed day was 56 days. Discharged in satisfactory condition with a completely healed wound.

Example 2. Extract from the medical history. Patient T., 46 years old, was admitted for treatment at MLPU City Emergency Hospital of Nizhny Novgorod 01/27/03 with a diagnosis of perforated gastric ulcer, acute renal failure. Concomitant diseases: coronary heart disease, myocardial infarction, postinfarction cardiosclerosis. He became acutely ill, there were spilled abdominal pains, lack of urine. On examination, the consciousness is clear, adequate, critical, distressed abdominal pain. Hemodynamics is stable. The abdomen is swollen, painful, mainly in the epigastric region, with positive symptoms of peritoneal irritation. In blood tests dated January 28, 03: hemoglobin - 103 g / l, leukocytes - 14.1 × 10 ⁹ / l, ESR - 66 mm / h, glucose - 6 mmol / l, total protein - 76.6 g / l, blood a-amylase - 54.6 mmol / L, AcAT / AlAT - 0.46 / 0.46, total bilirubin - 11.4 mmol / L, prothrombin index - 100%, urea - 29.4 mmol / L, creatinine - 0.178, K ⁺ / Na ⁺ - 6.6 / 132 mmol / L, leukocyte intoxication index - 20; medium molecules - 0.58. Operation - laparotomy, opening, tamponing, drainage of the stuffing box. Clinical diagnosis: focal fatty pancreatic necrosis, acute renal failure. In the early postoperative period, pneumothorax developed, for which microdrainage was performed on 01.28.03, and closed drainage of the right pleural cavity was performed on 01.30.03. Diuresis 1000-1500 ml with lasix stimulation. The course of the disease was complicated by the development of systemic multiple organ failure with a predominance of acute respiratory failure, acute heart failure, acute renal failure, endotoxemia of the I-II degree. On January 30, 2003, with the increasing effects of acute respiratory failure and acute heart failure, the patient was transferred to artificial lung ventilation. The intravenous drip of 1000 mg / day of ceruloplasmin was started. Against the background of intensive therapy with the use of iv infusions of ceruloplasmin, positive dynamics were noted during the disease and on 3.02.03, with satisfactory blood gas composition, stable hemodynamics, a clear mind, the patient was extubated and transferred to spontaneous breathing. Subsequently, in the course of treatment, the clinical manifestations of multiple organ failure syndrome were completely stopped in blood tests: hemoglobin - 100 g / l, leukocyte reduction - up to 10.2 · 10 ⁹ / l, glucose - 4.4 mmol / l, hypoproteinemia - 63 , 4 g / l, a decrease in blood α-amylase - up to 7.7 mmol / l and total bilirubin - up to 8.6 mmol / l. The effects of endotoxemia decreased: leukocyte intoxication index - 3.8 units, medium molecules - 0.26 units. An increased level of creatinine - 0.121 and urea - 20.3 mmol / l, but with a persistent tendency to decrease, remains. From the postoperative wound - without signs of infection. In a stable condition, the patient was transferred from the intensive care unit to the surgical department for further treatment. Bed-day in the intensive care unit - 14 days.

Example 3. Treatment of pancreatic necrosis without the use of ceruloplasmin. Extract from the medical history. Patient K., 63 years old, was treated at the MLPU City Emergency Hospital of Nizhny Novgorod from 05.20.02 to 05.07.02 with a diagnosis of infected pancreatic necrosis, retroperitoneal paracolic parapancreatic phlegmon. Received in serious condition of endotoxic shock with blood pressure of 70 mm Hg Clinically and by ultrasound - a picture of severe acute destructive pancreatitis. In blood tests: hemoglobin - 146 g / l, white blood cells - 7.1 × 10 ⁹ / l, ESR - 43 mm / h, C-reactive protein - 820, total protein - 75 g / l, total bilirubin - 22.0 mmol / l, prothrombin index - 83%, blood α-amylase - 31.7 mmol / l, AcAt / AlAT - 1.1 / 1.28, K ⁺ / Na ⁺ - 3.7 / 142 mmol / l, glucose - 6.9 mmol / l, urea 11.8 mmol / l, leukocyte intoxication index - 18.2, medium molecules - 0.68 units. Conducted conservative intensive therapy according to the accepted scheme. Stable positive dynamics were not observed. There was a deepening of endotoxemia and liver failure. In blood tests: leukocyte intoxication index - 97, medium molecules - 0.68, hypoproteinemia - 63 g / l, hyperbilirubinemia - 24.2 mmol / l, AcAT / AlAT - 1.33 / 0.46, prothrombin index - 82% hemoglobin - 100 g / l, ESR - 59-61 mm / hour. Mixed genesis encephalopathy was observed. Operation performed on 1.06.02: laparoscopy; sanitation of the abdominal cavity; bursomentostomy; sanitation, drainage of the stuffing bag. In the postoperative period, complex intensive therapy continued with the use of extracorporeal hemocorrection (3 plasmapheresis sessions, 7 sessions of indirect electrochemical blood oxidation), immunocorrection. Surgical treatment - programmed rehabilitation bursomentoscopy, sequestrectomy - only 8 operations. Despite the ongoing therapy, a sharp deterioration occurred in 06/25/02 — the formation of a small intestinal fistula with bleeding from the area of the pancreatic head. Stopping bleeding with conservative methods. On July 5, 02, repeated profuse bleeding from the splenic vein occurred. An operation was performed - laparotomy, vein ligation. Fatal outcome. Final diagnosis: infected pancreatic necrosis; pancreatogenic abscess; retroperitoneal abscess; paracolic, parapancreatic phlegmon on the right; small intestinal fistula; Arrosive bleeding from the splenic vein; portal hypertension; hypostatic pneumonia. Bed-day in intensive care unit - 22 bed-days, total bed-day - 48.

Claims (1)

A method for the pharmacological correction of endogenous intoxication in acute destructive pancreatitis, including basic therapy, characterized in that ceruloplasmin is administered at a dose of 600-1000 mg / day for 5 days in the complex treatment of acute destructive pancreatitis, with possible repeated courses.