RU2496493C1 - Method for prevention of acute postoperative pancreatitis - Google Patents

Abstract

FIELD: medicine.

SUBSTANCE: invention refers to medicine, namely to surgery, and may be used for prevention of acute postoperative pancreatitis. For this purpose, the underlying background therapy is combined with intravenous bolus administration of dalargin 0.002 g and the antioxidant thioctic acid depending on a risk level of the complication measured in terms of the area of intervention in abdominal operations. A high risk level requires thioctic acid to be administered in a dose of 600 mg intravenously drop-by-drop 1 hour before the operation and on the following day, and thioctic acid in a dose of 300 mg on the third day intravenously drop-by-drop. In a moderate risk level thioctic acid is administered intravenously drop-by-drop in a dose of 600 mg 1 hour before the operation and in a dose of 300 mg on the following day. And in a low risk level, thioctic acid is administered intravenously drop-by-drop in a dose of 300 mg 1 hour before the operation.

EFFECT: method enables the more effective prevention of acute postoperative pancreatitis ensured by the combined use of drugs with antisecretory and antioxidant activity.

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Description

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

The increase in the frequency of acute postoperative pancreatitis (AKI) is due to an increase in the number of complex and traumatic operations on the organs of the "upper floor" of the abdominal cavity. More often, postoperative pancreatitis develops after interventions on the pancreas itself, bile ducts, duodenum and spleen. Mortality in destructive forms of AKI is 50-85%. Timely diagnosis of this dangerous complication is difficult due to the abrasion of the clinical picture against the background of the underlying disease and previous surgery.

In recent years, pancreatic exocrine function blockers - sandostatin, octreotide (Shevchenko Yu.L., Vetshev P.S., Stoyko Yu.M., Levchuk A.L., Stepanyuk I.V.) have been widely used for prevention and in the complex treatment of AKI. The role of sandostatin in the prevention and complex treatment of acute postoperative pancreatitis // Annals of surgical hepatology. - 2008. - No. 3. - 82 pp. 23. Kassel B., Kau J. Zymogens of proteolitic enzymes // Science. - 1973. - Vol. 180).

Despite the improvement of medical equipment and the use of high-tech research methods, in the modern literature there is not enough data to draw up a diagnostic program for their consistent use in AKI. There is also no information about the effectiveness of the use of preventive measures in the pre- and postoperative periods to prevent the development of AKI.

It is worth noting that not in every work the effectiveness of research is given using the rules of evidence-based medicine. (24.P.lmariani A. Pharmacological Prevention of Post-ERCP Pancreatitis: Where Therapy is Best // J. Pancreas (Online). - 2003 - Vol.4, - N 1. - P.68-74. 022-1027 )

The pathogenesis of the early period of postoperative pancreatitis remains the subject of further scientific research. The mechanism that triggers a cascade of pathological reactions in this pathology remains debatable. In scientific papers, more attention is paid to hemocirculatory disorders in the pancreas and activation of lipid peroxidation (LPO) processes. It is believed that free radicals can have a direct proteolytic effect.

Given a new look at the pathogenesis of the early stage of AKI, work continues on the development of effective methods for the prevention of AKI.

In recent years, work has appeared on the prevention of acute postoperative pancreatitis in patients after operations on the organs of the upper floor of the abdominal cavity using antioxidants.

A known method for the prevention of acute postoperative pancreatitis proposed by Wollschlager S et al. The author recommends oral administration of 40 mg of prednisolone and 200 mg of allopurinol to inhibit oxidative processes before surgery.

This method has the following disadvantages: the use of glucocorticoid hormone is associated with a number of side effects characteristic of drugs of this group. Allopurinol, inhibiting xanthine oxidase. It does not affect other, more significant mechanisms of the formation of reactive oxygen species. In their study, the authors themselves indicated the low efficiency of the proposed method. (A prospective, randomized, placedo-controlled trial of prednisone and allopurinol in tne prevention of ERCP-induced pancreatitis. // Budzynska A, Marek T, Nowak A, Kaczor R, Nowakowska-Dulawa E / Endoscopy 2001 Sep; 33 (9): 766-72).

In order to prevent AKI after endoscopic retrograde pancreatocholangiography (ERCP), the use of IL 10 (Interleukin 10 reduces the incidence of pancreatitis after therapeutic endodoscopic retrograde cholangiopancreatography. // Deviere J, Le Moine O, Van Laethem JL, Eisendrath P, Ghiliain A Cohard M. Gastroenterology 2001 Feb; 120 (2): 498-505). The proposed drugs have a number of serious side effects and for preventive purposes cannot be applied to all patients. In addition, the cost of treatment is significantly exceeded, which limits the use of this method.

Closest to the claimed invention is a method for the prevention of postoperative pancreatitis (Shabanov V.V. "Acute postoperative pancreatitis: aspects of early phase pathogenesis and prevention (clinical and experimental research)" // Abstract of thesis, MD, Doctor of Medicine - Samara 2007. - 40 C.), taken by us as a prototype, consisting in the introduction of a CSR inhibitor - allopurinol. The drug was administered orally in two doses - 1/2 dose at bedtime on the eve of the day of surgery and 1/2 dose in the morning, 3 hours before surgery, at the rate of 50 mg / 10 kg of patient body weight. An analysis of the risks of developing acute postoperative pancreatitis in patients after laparoscopic cholecystectomy in the presented study revealed that the use of allopurinol for the prevention of acute postoperative pancreatitis in performing less traumatic operations, such as laparoscopic cholecystectomy, has shown sufficient effectiveness. However, the author himself comes to the conclusion that the use of this drug in patients with a high risk of postoperative pancreatitis is ineffective, which limits the use of this method of AKI prevention.

In order to increase the effectiveness of the prevention of acute postoperative pancreatitis, we propose a method based on a combination of the use of a drug with antisecretory activity and an antioxidant.

The invention is aimed at solving the problem of developing a method for the prevention of AKI depending on the degree of risk of its development, taking into account the pathogenesis of the early phase of acute pancreatitis, indicating the doses of the drugs used, the duration and frequency of their administration.

The solution to this problem provides our proposed method for the prevention of acute postoperative pancreatitis in operations on the abdominal organs, based on the combined use of an antioxidant - thiocic acid ("espa-lipon") with a drug with antisecretory activity - "dalargin", which allows to increase the effectiveness of the prevention of acute postoperative pancreatitis.

To achieve a technical result, a method has been developed for the prevention of acute postoperative pancreatitis, including basic therapy and an antioxidant, characterized in that thioctic acid is used as an antioxidant, used depending on the "risk" of complications, which is determined primarily by the area of intervention during operations on abdominal organs: pancreatic surgery - “high risk”, surgery on organs anatomically bordering the pancreas - “medium risk”, organ surgery ie related to the RV - "low risk." With a "high" risk, thioctic acid is administered 600 mg intravenously 1 hour before the operation and the next day, on the third day - 300 mg thioctic acid intravenously, with an "average" risk 600 mg thioctic acid intravenously an hour before surgery, the next day - 300 mg of thioctic acid intravenously, at a "low" risk level, 1 hour before surgery, 300 mg of thioctic acid are administered intravenously, and at the same time as thioctic acid, 0.002 g of dalar is used gina intravenously.

The method was carried out as follows: the effectiveness of AKI prevention was analyzed in 165 patients who were hospitalized in the surgical department of the SOGMA KB for inflammatory, chronic surgical diseases and oncopathology of the abdominal organs from 2010 to 2011. To solve the tasks, the patients were divided into two groups: the main group - 60; comparison group (control) - 105.

To determine the frequency of AKI and mortality depending on the area of intervention, patients were divided into three subgroups of the risk of developing AKI: subgroup I - patients after pancreatic surgery with "high risk"; Subgroup II - after operations on the abdominal organs, anatomically bordering the pancreas with “medium risk”; Subgroup III - patients after surgical interventions on the abdominal organs that are not anatomically related to the pancreas with a “low risk”.

The patients of the comparison group (n = 105) were given prophylaxis according to the scheme: 0.002 g of dalargin intravenously, 1 hour before surgery and in the next 2 days after surgery - I subgroup; 0.002 g of dalargin intravenously jet 1 hour before the intervention and the next day - II subgroup; 0.002 g of dalargin intravenously jet 1 hour before surgery once - III subgroup.

Patients of the main group (n = 60) are also divided into three subgroups (I - "high risk", II - "medium risk", III - "low risk"), in which prophylaxis was carried out according to the scheme: with a "high" risk level, thioctic 600 mg of acid is administered intravenously drip 1 hour before the operation and the next day, on the third day - 300 mg of thioctic acid intravenously, with an "average" risk - 600 mg of thioctic acid intravenously 1 hour before the operation, the next day - 300 mg of thioctic acid intravenously, with a "low" risk level for 1 hour before surgery, 300 mg of thioctic acid is administered intravenously, in addition, simultaneously with the administration of thioctic acid, 0.002 g of dalargin is administered intravenously.

The effectiveness of the use of a drug with antisecretory activity in combination with antioxidants in these groups of patients was assessed using laboratory tests (determining the activity of enzymes: amylase and blood lipase, urine diastases. Moreover, as an express method, a qualitative test was performed to detect trypsinogen-2 in urine - "actim Pancreatitis".) and instrumental (ultrasound, CT) research methods. The actim Pancreatitis test is based on immunochromatography. In this case, two different types of monoclonal antibodies with recognition of human trypsinogen-2 were used. This test allowed 80% of patients to detect AKI at an early stage of the disease. A marker of the degree of LPO activity in the patient's body was the concentration of malondialdehyde (MDA) in the blood.

In the study groups, an assessment of the concentration of MDA in the blood, the incidence of AKI, depending on the amount of surgery and overall mortality, was carried out. The research results are presented in tables No. 1 and 2.

The results of the analysis in the comparison group.

Table number 1. Subgroup amount AKI frequency Mortality abs. % abs. % I subgroup fifteen 2 13.3 one 6.67 II subgroup 65 5 7.7 one 1,53 III subgroup 25 one four 0 0 Total 105 8 7.6 2 1.9

The incidence of AKI of pancreatitis in the comparison group was 7.6% (n = 8), the total mortality rate was 1.9% (n = 2), the concentration of MDA in the blood was 1.24 ± 0.22 μmol / L (at a rate of 0 , 31 ± 0.02 μmol / L).

The results of the analysis in the main group.

Table number 2. Subgroup amount AKI frequency Mortality abs. % abs. % I subgroup 10 one 10 0 0 II subgroup 35 one 2.86 0 0 III subgroup fifteen 0 0 0 0 Total 60 2 3.33 0 0

The incidence of AKI of pancreatitis in the main group was 3.33% (n = 2), mortality - 0% (n = 0), the concentration of MDA in the blood was 0.76 ± 0.2 μmol / L.

Results: the use of the developed preventive schemes using thioctic acid and a drug with antisecretory activity allowed to reduce the incidence of AKI from 7.6% to 3.33%, and the total mortality rate from 1.9% to 0%.

The combined use of "dalargin" and thioctic acid ("espa-lipon") will reduce the concentration of lipid peroxidation products (malondialdehyde) by 37% and obtain a statistically significant improvement in the results of AKI prophylaxis.

The results of comparing the incidence of AKI in both groups are evidence of the effectiveness of the proposed method for the prevention of this complication.

According to the information available to the authors, the set of essential features characterizing the essence of the claimed invention is not known, which allows us to conclude that the invention meets the criterion of "novelty."

According to the authors, the essence of the claimed invention should not be obvious to specialists from a known level of medicine, since it does not reveal the above possibility of obtaining a method for reducing the incidence of acute postoperative pancreatitis, including basic therapy and an antioxidant, characterized in that thioctic acid is used as an antioxidant (“Espa-lipon”), in basic therapy, “dalargin” is administered depending on the volume and nature of the surgical intervention, which allows us to conclude that the criterion of "inventive step".

The set of essential features characterizing the essence of the invention can be repeatedly used in medicine to obtain a result that is an easy, affordable and effective way to prevent AKI by using the properties of the drugs used: blocking the production of IBS by an antioxidant, inhibiting the development of the cytokine cascade by a drug with antisecretory activity, in addition, the properties of dalargin as an anti-ulcer drug are widely known, so we can conclude that tvii invention to the criterion "industrial applicability".

We provide a description of three clinical observations:

Example 1

Patient B., 1935 g / r, and / b No. 6019, 10/25/2011, was routinely admitted to the surgical department with a diagnosis of PCES. Recurrent multiple choledocholithiasis. Condition after percutaneous transhepatic cholangiostomy. From the anamnesis: In 1984, cholecystectomy was performed from access according to Kocher. 08/12/11, in the Republican Clinical Hospital produced ChCHS about obstructive jaundice. At admission: a state of moderate severity. Body temperature is normal. The skin and visible mucous membranes of normal color. The vesicular breathing, no wheezing. NPV 18 min Heart tones are clear, the rhythm is correct. Heart rate 80 beats / min, blood pressure 110/80 mm Hg The tongue is wet. The abdomen is soft, not swollen, symmetrical, participates in breathing evenly. In the right hypochondrium of the cholangiostoma. Peristalsis is heard, satisfactory. There is no dullness in the sloping places of the abdomen. Palpation of the abdomen is painless. There are no symptoms of peritoneal irritation. Physiological settings are not broken. When performing fistulography, 2 calculi were revealed 10 * 8 and 8 * 6 mm in the terminal department of hepaticoholedoch. According to abdominal ultrasound, biliary hypertension with an expansion of the common bile duct up to 16.5 mm. In the lumen of hepaticoholedoch drainage. Laboratory indicators: OAK - erythrocytes - 3.79 * 10 ¹² / l, white blood cells - 7.4 * 10 ⁹ / l, hemoglobin - 123 g / l, s / I - 5.2 * 10 ⁹ / l, platelets - 247 * 10 ⁹ / l; Biochemical blood test - amylasemia - 52.7 U / L, total bilirubin 12.12 umol / L, glycemia - 5.41 mmol / L; coagulogram-prothrombin index 84%, fibrinogen - 3.4 g / l. Concomitant pathology: coronary heart disease. The angina is stable. FKSH. Postinfarction cardiosclerosis. Hi. Hypertension of the III degree, risk 4 (very high). The situation is described as a "high risk" of AKI, and therefore, on the day of surgery - November 1, 2011, prophylaxis was carried out according to the scheme: 600 mg of thioctic acid per 250 ml of isotonic sodium chloride iv solution 1 hour before surgery , in a similar dosage on the next day, on the third day, the dose is reduced to 300 mg of thioctic acid per 250 ml of isotonic sodium chloride solution - iv / c; The volume intervention was performed - fibrogastroduodenoscopy, endoscopic retrograde cholangiography. Endoscopic papillosphincterotomy, extraction of hepatic choledoch calculi. CHNVVJP. Using a Dormia basket, two stones were extracted into the lumen of 12p / gut. The calculus of a smaller caliber, due to severe pneumobilia, was not found and removed. External drainage of the bile ducts was transferred to the external-internal. In the postoperative period she received infusion, antisecretory, antispasmodic, hemostatic and analgesia according to indications. On the 3rd day, due to incomplete debridement of the bile ducts, a control fistulogaph was supposed to be performed to resolve the issue of removing the external-internal drainage and calculus extraction, which was performed on November 3, 2011, and the previously used prophylaxis scheme was again used. Produced by FGDS. Antegrade over-drainage cholangiography. Endoscopic extraction of calculus of the terminal department of hepaticoholedoch. Removal of external-internal drainage of the bile ducts.

The postoperative course is smooth, without a pain symptom, without septic disorders and pathological changes in laboratory blood parameters. On the 5th day, the patient in satisfactory condition was discharged from the hospital.

Example 2

Patient B., 50 years old, and / b No. 5584, was admitted to a surgical hospital with a diagnosis of cholelithiasis. Chronic calculous cholecystitis. Concomitant pathology: Hypertension II Art., Risk 3 (high)

From the anamnesis: periodically pain in the right hypochondrium and epigastrium

Surveyed on an outpatient basis - laboratory indicators of blood and urine within the physiological norm.

Consulted by a therapist, anesthetist - no contraindications to planned surgical intervention have been identified.

12.10.10, 1 hour before surgery - laparoscopic cholecystectomy - carried out prophylaxis according to the scheme corresponding to the "average risk" of AKI.

Macro drug: Gall bladder 7 * 2 cm, wall 0.1 cm, in the cavity of the bladder there are a lot of stones with rounded shape with a diameter from 0.4 to 1.0 cm.

The postoperative course is smooth. The seams are removed.

In satisfactory condition she was discharged from the hospital on the 4th day.

Example 3

Patient B., 18 years old, and b / w No. 5710 was admitted on an emergency basis with a preliminary diagnosis: Acute appendicitis

From the anamnesis: I did not take pain for 12 hours, I did not take any anesthetics on my own, and in connection with the intensification of the pain, I turned to an ambulance, which I was taken to the on-call clinic, hospitalized in the surgical department.

Objectively upon examination: a state of moderate severity. NPV 16 in min, pulse 70 in min, BP 120/80 mm Hg

The abdomen is soft, not swollen painful in the right iliac region. Peristaltic noises are heard, sonorous. Symptoms of Rovzing, Sitkovsky, Bartomier-Michelson, Voskresensky are positive. There are no peritoneal symptoms. Stool and urination are not broken.

Laboratory data: UAC erythrocytes 4.95 * 10 ¹² / l, white blood cells 6.6 * 10 ⁹ / l, hemoglobin 151 g / l, platelets - 211 * 10 ⁹ / l;

Blood biochemical analysis - glycemia - 5.0 mmol / l, amylase - 133 U / l, AST-23e, ALT-17e; urinalysis is the norm.

Diagnosed with acute appendicitis. The diagnosis is an indication for emergency surgical treatment in the amount of appendectomy. In order to prevent AKI, a “low risk” regimen has been assigned. On 10.10.10, an appendectomy was performed. Macro drug: vermiform appendix 8 * 0.5 cm - catarrhal appendicitis.

Postoperative course without features. The sutures were removed on the 7th day, the wound healed by primary intention. The patient was discharged from the hospital on the 7th day in a satisfactory condition.

Thus, based on our experience, the most effective method for the prevention of AKI is the use of a drug with antisecretory activity (dalargin) in combination with an antioxidant (thioctic acid) in a dosage corresponding to the “risk degree” of AKI. The results of the study indicate that adequate preoperative preparation, determining the degree of risk of AKI development (“low”, “medium” and “high”) before the main surgical intervention, allow you to choose an effective AKP prophylaxis program according to the proposed method, avoid and interrupt in the early stages of development, such a formidable postoperative complication as pancreatitis.

Claims (1)

A method for the prevention of acute postoperative pancreatitis, including basic therapy and an antioxidant, characterized in that thioctic acid is used as an antioxidant, used depending on the "risk" of the development of the complication, determined by the intervention area during operations on the abdominal organs: with a "high" risk thioctic acid is administered at a dose of 600 mg intravenously 1 hour before the operation and the next day, on the third day - 300 mg thioctic acid intravenously, with an “average” risk level - 600 mg of thioctic acid intravenously 1 hour before the operation, the next day - 300 mg of thioctic acid intravenously, with a “low” risk 1 hour before surgery, 300 mg of thioctic acid are administered intravenously, in addition simultaneously with the administration of thioctic acid 0.002 g of dalargin intravenously.