RU2762120C1 - Method for endoscopic hemostasis of bleeding gastroduodenal ulcer - Google Patents

Abstract

FIELD: medicine.

SUBSTANCE: invention relates to medicine, in particular to emergency surgery, and concerns the possibility of endoscopic hemostasis of a bleeding gastroduodenal ulcer. As a hemostatic agent, "Algistab" is used, which is applied to the source of ulcerative bleeding using a pneumatic insufflator. In this case, the amount of the applied drug "Algistab" is calculated by the formula: m=(0.7хD), where m is the amount of the drug "Algistab" (g), D is the diameter of the ulcer (cm).

EFFECT: method allows to enhance the hemostatic effect and shorten the healing time of gastric and duodenal ulcers.

1 cl, 1 tbl, 2 ex

Description

The invention relates to medicine, in particular to emergency surgery, and concerns the possibility of endoscopic hemostasis of a bleeding gastroduodenal ulcer.

The problem of treating gastrointestinal bleeding is an urgent problem in modern clinical practice. More than half of the cases of gastroduodenal bleeding occur in bleeding ulcers of the stomach and duodenum (duodenal ulcer) [Kachmazova A. V., Gioeva Z.A. Clinical and endoscopic assessment of gastrointestinal bleeding of ulcerative etiology // Norwegian Journal of the International Science. - 2020. - No. 39 (2). - S. 41-43].

The generally recognized leading method of treatment of gastroduodenal ulcers complicated by bleeding is endoscopic hemostasis in combination with hemostatic, antiulcer and anti-Helicobacter therapy. The use of methods for endoscopic stopping of gastroduodenal bleeding makes it possible to achieve final cessation of ulcerative bleeding in 79-97% of patients. However, the frequency of recurrence of hemorrhage even after successful stopping of bleeding reaches 10-46% of patients [Cherednikov E.F, Barannikov., S.V., Zhdanov A.I et al. Combined use of biologically active hemostatic and granulated sorbent in endoscopic cytoprotective hemostasis in patients with bleeding gastroduodenal ulcers // International journal of biomedicine.-2020.-Vol.10, N2.-P 129-132].

All methods of endoscopic hemostasis, depending on the type of effect on the source of bleeding, are divided into: injection, thermal, mechanical, application, etc. [Garelik P.V., Areshchenko K.V., Dubovshchik O.I., Marmysh G.G. ., Chervakova O. V., Shevchuk D. A. Gastroduodenal bleeding: the results of endoscopic hemostasis in a specialized city center // In the collection: actual problems of medicine, materials of the annual final scientific and practical conference. - Grodno, 2019. - P.142-145]. Thermal endohemostasis methods: mono-, bi- and multipolar electrocoagulation, argon-plasma coagulation, thermocouterization, laser photocoagulation, etc. have a damaging effect on the source of hemorrhage, which can lead to bleeding, as well as to perforation of the organ wall. When using injection methods, the infiltrate dissolves quickly, which leads to the resumption of hemorrhage. Methods of clipping vessels in an ulcer have significant technical limitations in hemostasis from chronic callous ulcers, in addition, 3-4 days after endohemostasis, the clip can be rejected, which leads to profuse recurrent bleeding [Lebedev N.V., Klimov A.E., Moroz V.A. Gastroduodenal bleeding. - M .: Publishing house BINOM, 2015. – 232 p.].

The known method of endoscopic hemostasis in gastro-duodenal bleeding by injecting the source of hemorrhage with a liquid to stop capillary bleeding "Hemostab" followed by argon plasma coagulation [RF Patent No. 249800]. The disadvantage of this method is the high cost of equipment required for medical endoscopy.

A known method for stopping ulcerative bleeding by applying to the source of hemorrhage powdered hemostatic systems Hemospray, EndoClot. However, these drugs are extremely expensive, which limits their clinical use [Vitali F., Naegel A., Atreya R., Zopf S., Neufert C., Siebler J., Neurath MF, Rath T. Comparison of Hemospray® and Endoclot ™ for the treatment of gastrointestinal bleeding. World J Gastroenterol.– 2019. – No 25 (13) .– P. 1592-1602].

Closest to the developed method is a method of treating gastroduodenal bleeding with endoscopic insufflation of helevin [Cherednikov EF Complex treatment of gastroduodenal ulcers using gel sorbents (clinical and experimental study): dis .... Dr. med. sciences. - 1998. - 210 s]. Disadvantages of the prototype: helevin does not have pronounced hemostatic properties, when used in the form of monotherapy, endoscopic hemostasis is short-lived, with possible recurrence of hemorrhages; helevin does not possess additional biological properties, which makes it impossible to influence the etiopathogenetic factors in the development of bleeding gastroduodenal ulcers. The specified method of treatment is close to the proposed, therefore, can be considered as a prototype.

Known hemostatic agents with multicomponent action. One of the effective hemostatic agents used in clinical practice is the powdered hemostatic algistab. Algistab is used as a local hemostatic when removing teeth, as well as removing dental deposits, curettage of periodontal pockets, removal of exostoses of alveolar processes, gingivectomy, microtraumas of the gums after taking dental impressions [Instructions for use "Material dental hemostatic antiseptic" Algistab "according to TU 9 49908538-2010 RU No. FSR 2010/08831 dated 10.09.2010 ". Found 02/05/2021 on the Internet at: http://omegadent.ru/catalog/gemostatiki]. On contact with blood, algistab forms a thick gel that puts pressure on the capillaries, keeping blood clots in place. Iodoform and methyl parahydroxybenzoate, which are part of the drug, give it antiseptic properties and increase its shelf life. Thus, the material dental hemostatic antiseptic algistab has the following properties: hemostatic activity, pronounced adhesive properties, hydrophilicity, the ability to turn into a thick hydrogel when applied to a bleeding surface, antiseptic properties, a powdery release form, which determines the possibility of its use in a new direction - for endoscopic hemostasis of a bleeding gastroduodenal ulcer.

Starting our own research, we did not find any works concerning the use of algistab for endoscopic stopping of gastroduodenal bleeding of ulcerative etiology.

It is proposed to use the powdered hemostatic agent algistab in a new direction - to stop bleeding from the gastroduodenal ulcer.

The technical result to be achieved by this invention is to improve the quality of treatment of patients with bleeding gastroduodenal ulcers by increasing the reliability of endohemostasis, reducing the frequency of recurrent bleeding, improving the timing and quality of healing of gastroduodenal ulcers.

To achieve the technical result, an in vivo experiment was carried out to study the possibility of using the powdered hemostatic agent algistab in the endoscopic treatment of simulated bleeding stomach defects.

An in vivo experiment was performed on 10 laboratory animals (dogs) weighing from 7 to 10.5 kg. The study was based on the previously described model of an experimental bleeding stomach defect [Cherednikov EF, Gryaznov VN, Baev VE, Gaponenkov DG. Modeling a bleeding stomach ulcer // Problems of forensic medicine and clinical practice. - Voronezh. - 1994. - S. 17-18].

The model of a bleeding stomach defect was reproduced as follows: animals under intravenous anesthesia (zoletil 100 - 7.5 mg / kg) during esophagogastroscopy were injected with 96% ethyl alcohol in an amount of 3.0 ml into the submucosal layer of the antrum of the animal's stomach. After that, vincristine (0.01 mg / kg of animal weight) was injected intravenously. On the 3-4th day after the injection of ethyl alcohol, the animals showed the development of a typical defect of the mucous-submucosal layer of the stomach 1.0 cm in diameter, rounded, the edges were edematous, infiltrated, the bottom was closed with fibrin and necrotic tissues. Bleeding from the area of the defect was reproduced by mechanical trauma to the bottom of the defect with biopsy forceps. In order to increase bleeding, a solution of heparin (100 U / kg of animal weight) was injected intravenously.

In experimental bleeding stomach defects, bleeding was stopped by pneumo insufflation of powdered algistab in an amount of 0.7 g from a distance of 1.0-1.5 cm from the surface of the simulated bleeding stomach defect. Control gastric defects were not treated and were used to assess the time of spontaneous stopping of bleeding and the timing of healing. Two hours after the esophagogastroscopy, the animals were given drink and dry food. Each animal underwent dynamic endoscopy with an interval of 2 days to visually assess the healing processes of the experimental and control defects. The results of the experiment were assessed according to the following indicators: the time of hemostasis, the presence of repeated bleeding, the timing and quality of healing of the simulated gastric defects. The results of the experimental study are presented in the table.

Experimental studies to study the hemostatic effect of powdered algistab in hemorrhages from simulated bleeding defects of the stomach in dogs showed that after pneumo-insufflation of powdered algistab, the time to achieve hemostasis in experimental defects was 6.0 (4.0; 8.0) sec at p <0, 01. It was noted that immediately after pneumo-insufflation, algistab was tightly fixed in the area of the bleeding defect, turning into a soft-elastic hydrogel. To assess the reliability of fixation of algistab to the surface of the gastric defect, a test was carried out by attempting to remove it with a stream of saline injected through an endoscopic catheter. The test showed that algistab was retained in the form of a hydrogel on the surface of the defect and its partial or complete removal from the defect was not observed. This circumstance made it possible to establish a new property of the drug algistab - strong fixation to the gastric mucosa.

Table - The effectiveness of the use of powdered hemostatic agent algistab in the endoscopic treatment of experimental bleeding stomach defects

Indicators Experience Me (Qw; Qn) Control Me (Qw; Qn) P-value Stop time
bleeding (sec) 6.0 (4.0; 8.0) 26.0 (25.5; 32.5) p <0.01 Abatement of inflammatory phenomena (days) 3.2 (3.4; 4.2) 9.0 (9.0; 10.0) p <0.01 Cleansing ulcers (days) 2.8 (2.5; 4.0) 6.2 (5.8; 6.4) p <0.01 The appearance of granulations (days) 3.0 (3.0; 4.0) 6.0 (6.2; 7.0) p <0.01 Epithelialization onset (days) 4.0 (3.2; 5.0) 9.0 (9.0; 10.0) p <0.01 Healing of ulcers (days) 8.2 (8.2; 8.5) 14.0 (12.0; 16.0) p <0.01

During dynamic endoscopic monitoring, it was noted that no complications or repeated bleeding were observed in the experimental defects, i.e. in them, hemostasis was reliable and final.

The stop of bleeding in the control was 26.0 (25.5; 32.5) sec (p <0.01). At the same time, in the control defects, 3 episodes of renewed hemorrhage were noted in the form of the appearance of clots or hematin at the bottom of the defect. Episodes of renewed bleeding in the control stopped on their own and did not require additional intervention.

Dynamic esophagogastroscopy of laboratory animals made it possible to establish that algistab remained on the surface of defects for up to 5-6 days, creating optimal conditions for reparative regeneration in experimental stomach defects. As can be seen from the data in the table, in the experimental defects, the inflammatory phenomena were less pronounced compared with the control and subsided by 3.2 (3.4; 4.2) days (p <0.01), the cleansing of the defects from fibrin and hematin was already taking place. on day 2.8 (2.5; 4.0) (p <0.01). The onset of the appearance of granulations was noted on day 3.0 (3.0; 4.0) (p <0.01), and marginal epithelialization was observed on day 4.0 (3.2; 5.0) (p <0.01 ). Experienced defects healed on 8.2 (8.2; 8.5) days (p <0.01) in 80.0% with the formation of a tender scar. The studies carried out made it possible to establish a new property of the drug algistab - the ability to shorten the time and improve the quality of healing of bleeding gastroduodenal ulcers.

In control defects, inflammation subsided by 9.0 (9.0; 10.0) days (p <0.01), ulcers were completely cleared of fibrin and hematin by 6.2 (5.8; 6.4) days ( p <0.01), the appearance of granulations occurred on 6.0 (6.2; 7.0) days (p <0.01). Control gastric defects completely healed in dogs on 14.0 (12.0; 16.0) days (p <0.01), and the healing of control ulcers in 90.0% occurred with the formation of a scar that grossly deforms the stomach wall.

The technical result is achieved by the fact that when carrying out therapeutic endoscopic hemostasis by pneumo-insufflation of powdered hemostatic agents on a bleeding gastroduodenal ulcer, it is new that the drug algistab is used as a hemostatic agent, which is applied using an endoscopic insufflator to a bleeding ulcerative defect in an amount determined using empirical of the established formula: m = (0.7xD), where: m is the amount of the drug algistab (g), D is the diameter of the ulcer defect (cm), from a distance of 1.0-1.5 cm from the surface of the source of hemorrhage. The use of the developed method makes it possible to obtain a new effect unknown from the prior art: increasing the reliability of endohemostasis, reducing the frequency of recurrent bleeding, cytoprotective effect, fixing the drug on the surface of ulcers for up to 5-6 days, improving the timing and quality of healing of gastroduodenal ulcers.

Clinical studies included 45 patients with gastroduodenal bleeding of ulcerative etiology, who were treated at the Voronezh City Specialized Center for the Treatment of Patients with Gastrointestinal Bleeding at the clinical base of the V.G. N.N. Burdenko of the Ministry of Health of Russia at BUZ VGKBSMP No. 1.

The effectiveness of treatment of patients was assessed by clinical, endoscopic and laboratory indicators: the criteria for the reliability of hemostasis (no signs of resumption of hemorrhage after endoscopic hemostasis according to the developed method), the frequency of recurrence of hemorrhages, prevention of emergency operations and mortality rates.

All patients, depending on the complex of therapeutic measures, were divided into two equivalent groups: the main group (n = 23 people) and the comparison group (n = 22 people).

Depending on the nature of the source of bleeding, the patients were distributed as follows:

Peptic ulcer of the stomach and duodenum, complicated by bleeding - 27 (60.0%) people (including 14 patients in the main group, 13 - in the comparison group).

Acute gastric and duodenal ulcer complicated by bleeding - 18 (40.0%) people (9 of them were patients in the main group, 9 were in the comparison group).

To assess the type of ulcerative bleeding, the classification of J. Forrest (1974) was used [Forrest JA, Finlayson ND, Shearman DJ. Endoscopy in gastrointestinal bleeding. Lancet. 1974; 2 (7877): 394-397], according to which the patients were distributed as follows: FIA, FIB-3 (6.67%) people (of which 2 - patients in the main group, 1 - comparison group), FIIA, FIIB - 31 (68.8%) people (of which - 16 patients in the main group, 15 - in the comparison group), FIIC - 11 (24.53%) people (of which - 5 patients in the main group, 6 - in the comparison group).

In the main group of patients, according to the developed treatment technology, against the background of general hemostatic, antiulcer, symptomatic therapies, endoscopic treatment was carried out by pneumo insufflation of powdered hemostatic algistab according to the developed method.

In the comparison group, traditional methods of endoscopic hemostasis were carried out in combination with conventional drug therapy, but without the use of pneumo-insufflation of hemostatic agents at the source of hemorrhage. Otherwise, the treatment of patients in the main group and the comparison group did not differ.

When assessing the results of treatment of patients in the main group, it should be noted that patients receiving treatment according to the developed technology, clinical and endoscopic remission of the disease occurred much earlier. As our studies have shown, immediately after pneumo insufflation of the hemostatic agent to the source of hemorrhage, algistab swelled, showed its hemostatic properties, turned into a powerful layer of hydrogel, was tightly fixed on the surface of the ulcer and was not washed off with a stream of saline. At the same time, the formed layer of soft elastic hydrogel protected the ulcer defect, the thrombosed vessel, the area of coagulation necrosis from the aggressive action of gastric juice and duodenal contents. During dynamic endoscopy, it was found that the hydrogel layer, due to the pronounced adhesive properties of algistab, lay on the defects for 5-6 days, providing a local hemostatic and cytoprotective effect, preventing the risk of renewed bleeding and creating optimal conditions for the healing of gastroduodenal ulcers.

In the final assessment of the effectiveness of treatment of patients with bleeding gastroduodenal ulcers, it was noted that in the main group the final hemostasis was achieved in all 23 patients. There were no signs of resumption of bleeding and urgent operations in this group. In the comparison group, final hemostasis was observed in 19 of 22 (86.4%) patients. Bleeding resumed in 3 (13.6%) patients. Emergency surgery was required in 1 of 22 (4.54%) patients.

Thus, a method has been developed that includes the use of a powdered hemostatic agent algistab in a new direction - for endoscopic hemostasis of a bleeding gastroduodenal ulcer. It should be noted that an important component of the method is the technique for achieving the technical result: the choice of a hemostatic agent, the dose of the drug, the method of application to the source of hemorrhage, the distance to the ulcer. The use of algistab for endoscopic hemostasis of a bleeding gastroduodenal ulcer enhances the hemostatic effect and shortens the healing time of gastric and duodenal ulcers.

To illustrate the above, we present clinical examples of patients who were treated at the Voronezh City Specialized Center for the Treatment of Patients with Gastrointestinal Bleeding (BUZ VO "VGKBSMP No. 1") and received endoscopic treatment according to the developed method.

Clinical example No. 1. Patient S., 45 years old, was admitted on February 2 in an ambulance with complaints of vomiting like "coffee grounds", black stools, general weakness. Suffering from peptic ulcer of the duodenum (DPC) for about ten years. He associates his illness with taking NSAIDs over the past four days.

On admission: the patient's condition is moderate. Pallor of the skin is noted. PS - 92 bpm, blood pressure - 105/65 mm. rt. Art. The abdomen is soft and painless. Rectally: feces on a black glove. Clinical blood test from February 02: hemoglobin - 45 g / l, erythrocytes - 1.6x10 ¹² / l, leukocytes - 8.8x10 ⁹ / l., Glucose - 6.7 mmol / l, total protein - 46 g / l, urea - 14.7 mmol / l, creatinine - 0.079 mmol / l, APTT - 23 sec, fibrinogen - 4.4 g / l, prothrombin index - 100%, thrombin time - 14 sec.

On an emergency EFGDS from February 02: The esophagus is not changed. The cardia rosette closes. The stomach contains a small amount of cloudy fluid. The folds are not high, longitudinally convoluted. The mucous membrane is not sharply thickened, slightly hyperemic. The gatekeeper is rounded, closed. A red dense blood clot is fixed on the anterior-upper wall of the duodenal bulb. It is difficult to estimate the size of the defect under it. For prophylactic purposes, the drug algistab in the amount of 1.0 g is insufflated per clot.

Conclusion: Chronic gastritis. Stopped bleeding from the duodenal bulb, most likely from an ulcer. Endoscopic treatment and prevention of bleeding with algistab.

In the ICU (e) of the general surgery department No. 1, the patient underwent general hemostatic, antiulcer and symptomatic therapy.

On February 03, the patient's condition is satisfactory. Complaints of general weakness. The hemodynamics are stable, the stool was after the enema. Clinical blood test: hemoglobin - 68 g / l, erythrocytes - 2.7x10 ¹² / l, leukocytes - 4.0x10 ⁹ / l.

On EFGDS No. 2772 dated February 05: in the duodenal bulb on the anterior wall, an ulcer measuring 1.3x0.8x0.1 cm, fibrin and hematin in the bottom. Pneumatic insufflation of the drug Algistab 0.9 g was performed on the area of the ulcer defect according to the proposed method. Conclusion: LDPK ulcer. There are no data for recurrent bleeding. Endoscopic treatment with algistab.

EFGDS dated February 08 (3 days after applying the drug algistab): the esophagus is passable, the stomach with symptoms of chronic gastritis in the stage of mild exacerbation. The ulcer of the duodenal bulb is about 1.2x0.5 cm, shallow, marginal epithelialization is noted, closed with fibrin and a soft-elastic hydrogel. HP express test - neg. Conclusion: The dynamics are positive.

On February 09, the patient's condition is satisfactory. No complaints. The abdomen is soft and painless. Stool and urination are not disturbed. In laboratory tests: hemoglobin - 72 g / l, erythrocytes - 2.26x10 ¹² / l, leukocytes - 4.4x10 ⁹ / l, glucose - 4.5 mmol / l, total protein - 58 g / l, urea -5, 0 mmol / L, APTT - 21 sec, fibrinogen - 2.9 g / L, prothrombin index - 88%, thrombin time - 15 sec.

At the insistence of the patient on 09.01.2019, he was discharged in satisfactory condition for outpatient treatment with recommendations. Spent 7 hospital beds / days.

Clinical example No. 2. Patient Sh., Was admitted on February 25 as an emergency with complaints of vomiting of "coffee grounds" and black stools. No ulcerative anamnesis. He associates his illness with stress.

On admission: the patient's condition is moderate. The skin and visible mucous membranes are pale pink. PS - 90 beats / min, blood pressure - 110/70 mm Hg. The abdomen is soft and painless. Rectally - black feces on the glove. In laboratory tests: hemoglobin - 93 g / l, erythrocytes - 3.13x10 ¹² / l, leukocytes - 12.6x10 ⁹ / l., APTT - 29 sec, fibrinogen - 1.8 g / l, prothrombin index - 86%, thrombin time - 18 sec, hematocrit - 32%.

EFGDS data from February 25: The stomach contains a moderate amount of hematin. The duodenal bulb is moderately cicatricially deformed, its mucous membrane is hyperemic, edematous. Inspection is extremely difficult due to constant regurgitation. It is impossible to fully straighten the gap. On the upper wall of the duodenal bulb, at the outlet, there is a fixed scarlet clot measuring about 0.7 cm in diameter, from under which a leak of scarlet blood is noted. With technical difficulties, an injection hemostasis was performed: 70.0 ml of saline and 2.0 ml of adrenaline were injected, the blood flow stopped. Argon plasma coagulation (APC) of the bottom of the ulcer was performed, after which pneumo-insufflation of the preparation Algistab 0.49 g was performed on the defect area according to the developed method. Conclusion: Ulcer of the duodenal bulb with signs of ongoing bleeding. Combined endoscopic hemostasis.

In the ICU (e) OXO-1, the patient underwent general hemostatic, infusion-transfusion and antiulcer (Nexium, Almagel) therapy.

On February 26, the patient's condition was of moderate severity, without deterioration. There was no vomiting or stool, and urination was not disturbed. Stable hemodynamics. Clinical blood test: hemoglobin - 77 g / l, erythrocytes - 2.92x10 ¹² / l, leukocytes - 5.4x10 ⁹ / l. On EGHDS # 561 dated 02/26/2019: The stomach contains a moderate amount of cloudy liquid and frothy mucus with bile, there is no blood and hematin. An ulcer of the duodenal bulb is about 1.0x0.6 cm in diameter, up to 0.2-0.25 cm deep, in the bottom there is a soft-elastic hydrogel, fibrin and hematin. Pneumatic insufflation of the drug Algistab 0.6 g was performed on the ulcer defect according to the developed method. Conclusion: There are no data for recurrent bleeding. Endoscopic treatment with algistab. Prevention of recurrent bleeding.

On February 28, the patient's condition is satisfactory. No complaints, no nausea and vomiting. The stool was after an enema, urination was not disturbed. Blood test: hemoglobin - 80 g / l, erythrocytes - 2.8x10 ¹² / l, leukocytes - 5.9x10 ⁹ / l.

With EFGDS 6 days after insufflation of algistab: There is no blood and hematin in the stomach. Ulcer of the duodenal bulb 0.6x0.4x0.1 cm, partially covered with hydrogel (30% of the area) and fibrin with elements of epithelialization from the edges and from the bottom. Additionally, Algistab 0.42 g was insufflated on the defect area according to the proposed method. Express help test "-" neg.

On March 4, the patient was discharged in satisfactory condition for outpatient treatment at the place of residence. The patient spent 7 beds / days in the hospital.

The study was supported by the Council for Grants of the President of the Russian Federation for State Support of Young Russian Scientists (MK-1069.2020.7 "Etiological, pathophysiological and therapeutic correlates of gastroduodenal bleeding: tactics of reducing complications and mortality in patients with urgent pathology").

Claims (1)

The method of endoscopic hemostasis of a bleeding gastroduodenal ulcer by using a powdered hemostatic to stop bleeding, characterized in that Algistab is used as a hemostatic agent, which is applied to the source of ulcerative bleeding using a pneumo-insufflator, while the amount of Algistab applied is calculated by the formula: m = (0.7xD), where m is the amount of the drug "Algistab" (g), D is the diameter of the ulcer (cm).