RU2006225C1 - Method of hemostasis in hemorrhagic gastritis - Google Patents

Abstract

FIELD: medicine, gastroenterology. SUBSTANCE: under condition of general hemostatic therapy cimetidine is administrated intravenously, and hemostatic mixture containing thrombin, aminocaproic acid, norepinephrine, barium sulfate and almagel is given orally to patient. Hemostatic mixture shows suspension consistency. EFFECT: enhanced efficacy and stability of hemostasis.

Description

 The invention relates to medicine, namely gastroenterology, and can be used for the conservative treatment of gastroduodenal bleeding due to hemorrhagic gastritis.

 The invention can be used for gastroduodenal hemorrhages of another etiology, however, for bleeding from arrozed vessels in case of peptic ulcer, rupture of varicose veins of the esophagus and stomach with portal hypertension, Mallory-Weiss syndrome and other diseases, this method can be used in the presence of dynamic fibrogastroscopic control and only as one of components of hemostatic therapy.

 A known method of hemostasis in hemorrhagic gastritis by intensive therapy, including antacids.

 The disadvantage of this method is not high enough efficiency (85.9%).

 A known method of stopping gastroduodenal bleeding using somatostatin.

 The disadvantage of this method is the lack of production and high cost of the drug, which does not allow its use in widespread practice.

 A known method of treating gastroduodenal bleeding by local irrigation with a solution of norepinephrine / Le Veen et al. 1972 /.

 The disadvantage of this method is its low efficiency (66.6%) and insufficient stability of hemostasis.

 A known method of treating gastroduodenal bleeding using a thrombinofibrin drug, applied topically.

 The disadvantage of this method is not sufficiently high efficiency (94.9%) and a high probability of recurrence of bleeding.

 Closest to the proposed method in its technical essence and the achieved positive effect is a method of treating gastroduodenal bleeding by local exposure to a mixture of aminocaproic acid and thrombin during the day.

 The disadvantage of this method is the fact that it turned out to be quite effective only in patients with mild and moderate bleeding, while in patients with severe bleeding its effectiveness is 85.7%. Moreover, with the preserved secretion of gastric juice with this method, there is a real danger of recurrence of bleeding due to the action of hydrochloric acid and proteolytic enzymes on the clot.

 The purpose of the invention is to increase the efficiency and stability of hemostasis.

 The goal is achieved as follows.

 A patient with gastric bleeding with hemorrhagic gastritis on the background of standard hemostatic therapy (replenishment of blood loss, the introduction of vikasol, calcium chloride, dicinone, adroxon, aminocaproic acid, fibrinogen) is injected with a per os hemostatic mixture, which includes thrombin and aminocarponic acid, with a distinctive moment the fact that cimetidine (histodil) is administered intravenously to the patient, and the hemostatic mixture additionally contains norepinephrine, barium sulfate, almagel and has a consistency of weigh.

 Justification of the parameters of the method.

At the preliminary stages of the development of the method, various options for introducing the proposed mixture were tested. The most optimal was the following version of Barium sulfate 45 - 50 g
Aminocaproic acid 5% 95 - 100 ml Thrombin - 950 - 1000 units; Norepinephrine hydrotartrate 0.2% 1.8 - 2.0 ml Almagel 50 - 60 ml
The use of a hemostatic mixture with a deviation from these parameters is impractical, since this does not lead to the achievement of a more pronounced positive result.

 Barium sulfate in a dose of 45 - 50 g, suspended in 100 ml of aminocaproic acid solution with a mixer, forms a liquid suspension, convenient for oral administration. Adding 50-60 ml of almagel to this mixture and thorough mixing in a mixer (for 3 minutes) stabilizes the hemostatic mixture. A single dose of 80-100 ml of the mixture, and then every 1.5 - 2 hours, 15 ml (word spoon) provides round-the-clock contact of barium hemostatic suspension with the gastric mucosa. Since 300-320 ml of a hemostatic mixture is required during the day, the dose of barium sulfate is 95-100 g, which is completely harmless to the patient and corresponds to a single dose during an X-ray examination of the stomach.

 The dose of aminocaproic acid (5% - 95 - 100 ml) corresponds to a single dose, which is allowed by pharmacopoeia for intravenous administration. Aminocaproic acid, containing a suspension of barium sulfate and insoluble salts of aluminum and magnesium, does not lose its properties - inhibition of fibrinolysis, therefore its presence in the hemostatic mixture ensures the stability of hemostasis. Since the patient receives 300 - 320 ml of this mixture per day, the dose of aminocaproic acid is 10 - 11 g, which corresponds to the average daily dose.

 When taken by mouth, norepinephrine hydrotartrate does not have a general effect, and in the gastric juice, rapidly oxidizing, it loses its vasoconstrictor effect, therefore, only its systematic administration together with the hemostatic mixture, which provides alkalization and neutralization of the peptic activity of gastric juice, in the indicated concentration creates the conditions for persistent spasm of small vessels.

 Almagel, which is part of the hemostatic mixture, provides alkalization of the acidic contents of the stomach and neutralization of the peptic activity of gastric juice, and these are the necessary conditions for local hemostasis.

 Almagel in the specified dose provides stabilization of the hemostatic suspension in the form of a gel. Thus, a suspension of barium sulfate in a solution of aminocaproic acid with thrombin and norepinephrine, prepared in a mixer for 3 minutes, begins to delaminate (sedimentation of barium sulfate) after an average of 1.51 ± 0.03 minutes, while the addition of almagel in the indicated dose leads to a sharp slowdown in this process, stratification begins after 23.1 ± 0.38 min (P <0.001).

 The sedimentation rate of barium sulfate in the mixture without almagel was 16.70 ± 0.30 mm / h, while in the mixture with the addition of almagel, the sedimentation rate of barium sulfate was 5.0 ± 0.30 mm / h. (P <0.001). Thus, the addition of almagel to the hemostatic mixture provides conditions for blood coagulation, reduces the likelihood of lysis of the formed blood clot, and increases the contact time of the hemostatic mixture with the gastric mucosa due to the enveloping effect and stabilization of the hemostatic mixture. The dosage form of the gel creates the conditions for a uniform distribution over the gastric mucosa and a longer effect.

 The content of aluminum hydroxide and magnesium oxide in 50-60 ml of almagel is approximately half the daily dose, and since the patient received 300 to 320 ml of a hemostatic mixture of the specified composition during the day, it is therefore impossible to increase the dose of almagel. Irrational and reduce the amount of almagel.

 Reducing the hyperacidity of gastric juice is also achieved by the use of cimetidine (histodil) 10% - 2 ml intravenously, repeating injections after 6 hours, which corresponds to the average daily dose.

 The introduction of the proposed mixture should last an average of 48 - 50 hours. This period is justified by the fact that hemorrhagic gastritis can develop both against the background of an intact mucosa and with its erosive lesions. And as you know, when eliminating the ethnological factor, erosion is usually eliminated after 48 hours.

 Conformity of the proposed technical solution to the criterion of "novelty."

 When comparing the claimed technical solution with the prototype revealed its new significant features, the essence of which at the filing date of the application was not disclosed in the USSR and abroad. Checking and analyzing sources of information and patent documents for the corresponding and related classes of MKI did not reveal technical solutions that discredit the novelty of the claimed subject matter of the invention — increasing the therapeutic effect by using a water-insoluble base that is saturated with hemostatic preparations and stabilizes in the form of a gel, which gives reason to consider it appropriate the criterion of "novelty."

 Confirmation of compliance of the proposed technical solution with the criterion of "significant differences".

 When analyzing the sources of information identified technical solutions in which there are signs similar to those that distinguish the claimed solution from the prototype. We provide a comparison of the properties of the claimed and known technical solutions due to the presence of the indicated features in them.

 It is known to use barium sulfate as a contrast agent for X-ray examination of the esophagus, stomach, intestines in the form of a suspension in water (100 g of barium sulfate and 150 - 200 ml of distilled water).

 It is known to use a paste containing 50% barium sulfate for x-ray studies.

 Thus, the sources cited do not contain information on the possibility of using barium sulfate as the basis of a hemostatic mixture.

 It is known to use barium sulfate in enterocutaneous fistula as a means of stimulating the proliferation of granulation tissue, which leads to an increase in the effectiveness of conservative treatment.

 Based on the analysis, it was found that the possibility of the manifestation of such properties of barium sulfate as the enhancement of the hemostatic effect of known hemostatic agents in the local treatment of gastroduodenal bleeding associated with hemorrhagic gastritis according to the claimed formula does not follow from the information known to the applicant on the regulatory list of legal sources.

 Therefore, the claimed object of the invention has significant differences, since it appears properties that do not match the properties of known technical solutions.

 The method is as follows.

 Upon admission of a patient with gastroduodenal bleeding to the hospital, fibrogastroscopy is performed - the diagnosis and source of bleeding are established.

 Patients with hemorrhagic gastritis are prescribed standard hemostatic therapy (gastric lavage with cold water, replenishment of blood loss - according to indications, administration of calcium chloride, dicinone, hadroxone, aminocaproic acid, fibrinogen, vicasol), 200 mg cimetidine (histodil) is administered every two hours for 2 hours days, 50-60 ml of the proposed hemostatic mixture is injected through the mouth, which is thoroughly shaken with a mixer for 3 minutes before use. In the first 3 hours every hour, and then every 1.5 - 2 hours, one tablespoon (15 ml) of the indicated hemostatic mixture is administered through the mouth for 48 hours. Food is prohibited for the duration of treatment (48 hours); liquid intake through the mouth is limited to two glasses of 1 - 2% baking soda solution. Water-electrolyte needs are met within two days by intravenous administration of polyionic solutions and glucose solution. After 24 hours and 48 hours, control fibrogastroscopy was performed. Based on endoscopic data, the effectiveness of the therapy is judged. The advantages of the proposed method are that against the background of activation of hemostasis and constant inhibition of the secretory activity of the stomach, it provides long-term contact with the gastric mucosa of the drug suspension, which simultaneously neutralizes the gastric juice, spasm of the vessels and a pronounced hemostatic effect.

 Examples confirming the possibility of carrying out the invention with a positive effect when using the totality of the essential features of the invention indicated in its formula.

 PRI me R 1. Patient Z., 79 years. , was admitted to the surgical department with a diagnosis of erosive hemorrhagic gastritis, active bleeding. Upon receipt of a complaint of general weakness, black stool, vomiting with blood clots.

 An objective examination: a state of moderate severity, skin and visible mucous membranes are pale. Pulse 88 beats in 1 min, satisfactory filling, blood pressure 150/80 mm RT. Art. The tongue is covered with a gray coating, the abdomen of the correct configuration, evenly participates in the act of breathing, soft, moderately painful in the epigastric region, tarry stools.

Blood test: red blood cells 1.90 x ^{10 12} / l, hemoglobin - 65 g / l, hematocrit 0.20. On the day of admission, fibrogastroscopy was performed - erosive hemorrhagic gastritis, active bleeding.

 Treatment: histodil 10% 3 ml intravenously after six hours, transfusion of erythrocyte suspension. After washing the stomach cavity from blood clots with cold water, the patient in a lying position on the left side takes 50 ml of a mixture of the following composition through the mouth: aminocaproic acid 5% 100 ml, barium sulfate 50 g, norepinephrine 0.2% 2 ml, thrombin 1000 units, almagel 60 ml, subsequently this mixture is taken after 1.5 - 2 hours, 1 tablespoon per day.

 After a day, there are no signs of ongoing bleeding.

 Hemostatic therapy continues.

 With control fibrogastroscopy in a day - in the stomach contents mixed with bile, in the upper third of the body of the stomach remains erosion of 0.2 x 0.5 cm, covered with light fibrion. The mucous membrane in the antrum and fundus is pale, atrophic.

Complete blood count after 7 days: red blood cells - 3.9 x 10 ¹² / l, hemoglobin - 130 g / l, white blood cells - 5.0 x 10 ⁹ / l, ESR - 10 mm / h, p-1, s-69 , e-6, m-3, l-21.

The treatment effect is stable hemostasis. Continued treatment of gastritis.
PRI me R 2. Patient E., 27 years old, was admitted to the surgical department with a diagnosis of erosive reflux esophagitis. Hemorrhagic gastritis. Bleeding.

 At admission, she complained of pain in the epigastric region, aggravated during meals, nausea, vomiting with an admixture of blood, general weakness.

 An objective examination: the condition is satisfactory, the skin is pale in color. The pulse of 96 beats in 1 min, rhythmic blood pressure 90/60 mm RT. Art. The abdomen is involved in the act of breathing, with palpation soft, painful in the epigastric region, the stool is of normal color.

Blood test: red blood cells - 3.6 x10 ¹² / l, hemoglobin - 126.3 g / l, hematocrit - 0.35.

 Fibrogastroscopy upon admission - signs of a hiatal hernia, erosive reflux azophagitis, hemorrhagic gastritis, active bleeding.

 Treatment: histodil 10% 2 ml intravenously, vicasol 1% 2 ml, adroxon 0.025% 1 ml intramuscularly. In the supine position, the patient takes 60 ml of the mixture inside: aminocaproic acid 5% 95 ml, barium sulfate 49 g, norepinephrine 0.2% 1.9 ml, thrombin 950 units, almagel 50 ml, then this mixture was taken through 2 - 2.5 hours, 1 tablespoon.

 In the following days, there were no signs of ongoing bleeding. Vomiting has stopped.

Blood test after 3 days: red blood cells - 3.9 x 10 ¹² /, hemoglobin - 133 g / l, white blood cells - 5.2 x 10 ⁹ / l, ESR - 28 mm / h.

 Repeated esophagogastroduodenoscopy - in the esophagus the amount of erosion is slightly less, in the stomach there is a moderate amount of light mucous contents in the antrum with focal atrophy and a small amount of erosion, in the remaining sections it is unevenly hyperemic.

 The treatment effect is stable hemostasis.

 PRI me R 3. Patient I., 32 years old, was admitted to the surgical department with a diagnosis of hemorrhagic gastritis. Gastric bleeding. On admission, the patient complained of pain in the epigastric region, right hypochondrium, nausea, vomiting with an admixture of blood, general weakness, dizziness, black "tarry" stool.

 An objective examination: a state of moderate severity. The skin and visible mucous membranes are pale in color. Heart sounds are rhythmic, pulse of 100 beats in 1 min, blood pressure 140/90 mm RT. Art. The abdomen is involved in the act of breathing, soft, painful in the epigastric and right hypochondrium, the stool is “tarry”.

Blood test: red blood cells - 3.2 x 10 ¹² / l, hemoglobin - 94 g / l, white blood cells - 4.6 x 10 ⁹ / l.

 Fibrogastroscopy on the day of admission - hemorrhagic gastritis, cicatricial-ulcerative deformity of the pylorobulbar zone, gastric bleeding. Hernia of the esophagus.

 Treatment: the stomach is washed with cold water, histodil 10% 2 ml intravenously after 6 days, vikasol 1% 3 ml intramuscularly, adroxon 0.025% 2 ml intramuscularly, red blood cell transfusion. In a horizontal position on the left side, it takes 60 ml of a mixture of the following composition: aminocaproic acid 5% 90 ml, barium sulfate 45 g, norepinephrine 0.2% 2 ml, thrombin 950 units. almagel 50 ml, then takes this mixture for 3 hours every hour, and then after 1.5 - 2 hours, 1 tablespoon for two days.

 After a day, there is no data for ongoing bleeding. Hemostatic therapy continues.

 Fibrogastroscopy after 2 days - in the stomach, empty stomach contents mixed with bile. The gastric mucosa is hypertrophied, pink. The duodenal bulb is deformed, its mucosa is focal hyperemic.

Blood analysis after 6 days: red blood cells - 3.5 x 10 ¹² / l, hemoglobin - 118.4 g / l, white blood cells - 4.1 x 10 ⁹ / l, ESR - 30 mm / h.

 Treatment effect - stable hemostasis is achieved.

 Continued treatment of gastritis, bulbitis.

When using the proposed method, a positive effect was achieved, expressed as a goal of the invention, namely:
- increased efficiency up to 100% compared with 85.7% in the prototype;
- increased stability of hemostasis, due to the fact that barium sulfate, introduced into the stomach in the form of a suspension, is delayed on the mucosa and its folds up to 90 - 120 minutes or more. With the introduction of the mixture after 1.5 - 2 hours, its constant contact with the gastric mucosa is ensured. When using the proposed method, recurrence of bleeding during treatment was not observed.

 Treatment by the proposed method was subjected to 18 patients. In all cases, stable hemostasis was achieved, confirmed by fibrogastroscopic studies.

 The growth method is in execution and can be carried out in any medical institution that has endoscopic devices. The method involves the use of not scarce domestic drugs. (56) Usmansky M.A. et al. Bulletin of Surgery, 1971, v. 107, 8, p. 14-19.

Claims (1)

METHOD FOR HEMOSTASIS IN HEMORRHAGIC GASTRITIS by oral administration of a hemostatic mixture containing thrombin and aminocaproic acid, against the background of general hemostatic therapy, characterized in that, in order to increase the effectiveness and stability of hemostasis, cimetidi is administered intravenously, and the hemostatic mixture additionally contains noradrenaline, barium Almagel with the following components:
Thrombin 950 - 1000 units
Aminocaproic acid 95 - 100 ml of a 5% solution
Norepinephrine 1.8 - 2.0 ml 0.2% solution
Barium sulfate 45 - 50 g
Almagel 50 - 60 ml,
at the same time, 80-100 ml of the mixture are injected simultaneously, and then 15 ml every 1.5-2 hours.