MD1848Z - Method for endoscopic hemostasis of variceal hemorrhages in liver cirrhosis - Google Patents

Abstract

The invention relates to medicine, especially to surgery and hepatology, and can be used for endoscopic hemostasis of esophagogastric bleeding from varicose veins in decompensated liver cirrhosis. The essence of the invention consists in installing a Sengstaken-Blakemore nasogastric tube, washing the stomach for 10 ... 15 minutes by introducing 1 ... 2 liters of water at a temperature of 10 ... 12 ° C, then after 24 hours the tube is removed, after which, using an endoscope at the level of the esophagogastric junction in the retrograde and anterograde directions, fibrin glue is introduced, which includes two components that are introduced separately by mixing them into the lumen of the vessel, namely, the first component includes a fibrinogen solution, and the second component includes a mixture of thrombin solutions with a 10% solution of albumin, aprotinin and Ca + 2 chloride, in the following ratio components, per 1 ml: fibrinogen solution (mg) 15...45 thrombin solution (U) 25...100 10% albumin solution (ml) 10...20 aprotinin solution (AKE) 250...1000 Ca+2 chloride solution (μmol) 15...30, then an endoscope with a device for applying elastic bands is inserted into the esophagus and varicose veins of the esophagus are ligated with elastic bands.

Description

[0001] The invention relates to medicine, in particular to surgery and hepatology, and can be used for endoscopic hemostasis of esophageal-gastric variceal bleeding in decompensated liver cirrhosis.

[0002] The progressive evolution of portal hypertension (HP) of cirrhosis determines a series of compensatory-adaptive reactions and leads to the development of collateral hemocirculation through porto-systemic anastomoses, one of these clinical manifestations representing the formation of esophageal-gastric varices (EGV), an asymptomatic complication, which carries an increased subsequent risk (Bhasin D., 2004; Бебуришвили А., 2006). Esophageal varices occur in the case of excessive portal pressure, which finds a way to resolve through the gastric coronary vein and shunting of venous flow into the veins of the esophageal submucosa, while gastric varices are determined by the diversion of portal blood flow through the short gastric veins of the spleen (Sarin S., 2001).

[0003] An important role in establishing the pathogenetic treatment of EEG is attributed to the morphofunctional peculiarities of the esophageal venous plexuses, the implementation of endoscopic USG contributes to the study of hemocirculation on the azygos vein with the assessment of abnormalities of periesophageal venous collaterals and perforating veins (Irisava A., 2001; Sato T., 2004).

[0004] Esophageal-gastric variceal hemorrhages represent the most serious complication of cirrhotic HP, most authors considering them as a key problem of liver cirrhosis. According to (Sharara A., 2001, De Francis R., 2000, Burroughs A., 2001) during 2 years after the appearance of VEG about. 25…30% of cirrhotic patients develop variceal hemorrhagic accident, resulting in a high lethality (30…80%), determined by the functional liver reserves and simultaneously independent of the therapeutic measures performed (Rikkers L.,1998; Щїголев A., 2002; Аль-Сабунчи О., 2007). Over the last decades, attempts have been made to establish risk criteria for the onset of variceal hemorrhages, with the NIEC index being proposed in 1988, which has proven to be quite sensitive in predicting them (Merkel C., 2000). It is estimated that the most important factors are represented by: 1) Degree of dilation, shape and extension of the variceal cord; 2) "Red color signs", or so-called endoscopic markers, due to thinning of the distended variceal wall by excessive portal pressure; 3) Functional liver status.

[0005] Digestive hemorrhages due to rupture of the esophageal varices are one of the most serious and dramatic complications of surgical HP. (Burrhougs A., 2001) indicates that in the first 6 months after the initiation of the primary hemorrhagic accident the overall mortality is 27%, while after 6 months according to the results of other authors this index includes drastic limits of 40…60% (Korula J. Technique of endoscopic sclerotherapy. Gastroenterologic Endoscopy. Philadelphia. W.B. Sounders Co., 2000, p. 371-388; Westaby D., Macdougall B.R.D., Williams R. Improved survival following injection sclerotherapy for esophageal varices: final analysis of a controlled trial. Hepatology 1985, vol. 5(2), p. 827-830). This fact is explained by a high recurrence rate of variceal hemorrhages of 30…40% (McCormick P.A., O'Keefe C. Improving prognosis following a first variceal hemorrhage over four decades. Gut 2001, vol. 49(6), p. 682-685), with days 7…10 of the posthemorrhagic period being considered critical. The prognosis of variceal hemorrhages is much bleaker when they occur in cirrhotic patients with a severely altered liver status. The probability of survival in the critical period of 6 months after hemorrhage in Child "A" patients is 80%, in patients of the Child "B" functional class it is 50…60%, compared to 15 percent of cases in patients of the Child "C" category. Improving outcomes in this high-risk group of patients can only be achieved through early hemostasis and prevention of bleeding relapses (Bhasin D.K., Siyad I. Variceal bleeding and portal hypertension: new lights on old horizont. Endoscopy 2004, vol. 36(2), p. 120-129; Burroughs A.K., Patch D. Management of variceal haemorrhage in cirrhotic patients. Gut 2001, vol. 48(7), p. 738-740; Gatta A., Sacerdoti D., Bolognesi M., Merkel C. Portal hypertension: State of art. Italian J. Gastroenter. & Hepatology 1999, vol. 31(4), p. 326-345).

[0006] The method of endoscopic hemostasis of surgical variceal hemorrhages using an alcoholic solution of sodium tetradecyl sulfate, which causes vessel sclerosis, is known [1].

[0007] The disadvantages of the varicose vein sclerotherapy method are the ineffectiveness of its use in the case of large-caliber varicose veins, causing pronounced pain after use and in some cases local necrosis with severe complications, namely perforations of the esophagus, mediastinitis, frequent relapses of repeated hemorrhages, and at a distance it can be complicated with esophageal stenosis as a result of sclero-atrophic processes after repeated manipulations.

[0008] The method of using fibrin glue for endoscopic hemostasis of variceal hemorrhages in liver cirrhosis is known, which is composed of fibrinogen, coagulation factor XIII, fibronectin, plasminogen and aprotinin, which are mixed with solutions of thrombin and Ca+2 chloride, in the following ratio of components, per 1 ml:

Fibrinogen (mg) 70...110

[0010] factor XIII (IU) 10...50

[0011] fibronectin (mg) 2...9

plasminogen (mg) 20...120

[0013] aprotinin (KIU) 3000

[0014] thrombin (IU) 500

[0015] Ca+2 chloride (µmol) 40 [2].

[0016] The disadvantages of the known fibrin glue are that its polymerization occurs immediately after the components are combined, which does not allow its introduction into the lumen of the bleeding variceal vein through the injection catheter of the 150 cm long endoscope, due to the rapid polymerization of the compound with occlusion of the catheter lumen, poor adhesion to the vascular wall and risk of spontaneous expulsion of the fibrin clot.

[0017] The method of hemostasis of variceal hemorrhages by ligating the varices with elastic bands using an application device, which is fixed on the endoscope, is also known [3].

[0018] The disadvantages of the mentioned method are that elastic ligatures cannot be applied in case of bleeding from fundic gastric varices, due to the limited maneuverability of the endoscope applicator, and in case of large-caliber varices (>1 cm) during the application of ligatures, the variceal wall may be damaged, causing profuse bleeding.

[0019] The method of endoscopic hemostasis of variceal hemorrhages is known by using fibrin glue, which contains fibrinogen solution, which is mixed with solutions of aprotinin, thrombin, Ca+2 chloride and adrenaline, in the following ratio of components, per 1 ml:

[0020] fibrinogen solution (mg) 15...30

[0021] aprotinin solution (KIU) 250...1000

[0022] thrombin solution (IU) 25...100

[0023] Ca+2 chloride solution (µmol) 15...30

[0024] adrenaline solution (mg) 0.1...0.3 [4].

[0025] The disadvantages of the method are that when injecting the components of the adhesive into bleeding varicose veins with the formation of a fibrin clot, spontaneous expulsion of the clot from the lumen of the vessel may occur due to high venous pressure, the soft gelatinous consistency of the formed fibrin clot and its reduced fixation to the vascular wall. At the same time, a disadvantage is the excessive cost of the fibrin adhesive, namely of the component, such as fibrinogen.

[0026] The problem solved by the invention consists in developing a method for endoscopic hemostasis of variceal hemorrhages in decompensated liver cirrhosis, which would eliminate the aforementioned disadvantages by using a fibrin adhesive, which allows for effective hemostasis with the formation of a hard and stable clot, with a long retraction capacity using a reduced amount of adhesive in hard-to-reach areas of the stomach and the use of other methods in accessible areas, which would reduce the cost of treatment, which will lead to the formation of extraluminal paraesophageal collaterals and the prophylaxis of repeated variceal hemorrhages.

[0027] The essence of the invention consists in installing the Sengstaken-Blakemore nasogastric tube, performing gastric lavage for 10…15 min by introducing 1…2 L of water with a temperature of 10…12°C, then after 24 hours the said tube is removed, after which with the help of the endoscope at the level of the esophageal-gastric junction a fibrin adhesive is injected into the fundic gastric varices in the retrograde and anterograde direction, which includes two components, which are introduced separately with their mixing into the lumen of the vessel, namely the first component includes a fibrinogen solution, and the second component includes a mixture of thrombin solutions with 10% albumin solution, aprotinin and Ca+2 chloride, in the following ratio of components, per 1 ml:

Fibrinogen (mg) 15...45

[0029] thrombin (IU) 25...100

[0030] 10% albumin solution (ml) 10...20

[0031] aprotinin (KIU) 250...1000

[0032] Ca+2 chloride (µmol) 15...30,

[0033] The endoscope with the elastic band application device is then inserted into the esophagus and the esophageal varices are ligated with elastic bands.

[0034] The result of the invention is that it allows for efficient hemostasis with avoidance of spontaneous expulsion of the fibrin clot, efficient adhesion to the vascular wall, due to obtaining a clot of a hard consistency with a long retraction capacity in hard-to-reach areas, namely in fundic gastric varices, and efficient and inexpensive mechanical hemostasis of esophageal varices, which lead to the formation of paraesophageal extraluminal collaterals and the prophylaxis of repeated variceal hemorrhages.

[0035] Advantages of the invention:

[0036] - obtaining a fibrin clot of a hard consistency;

[0037] - secure attachment to the inner walls of the varicose vein;

[0038] - formation of a consistent fibrin plug;

[0039] - due to the hard consistency, the biological degradation period of the curd is long;

[0040] - formation of extraluminal paraesophageal collaterals;

[0041] - avoiding hemorrhagic relapses;

[0042] - affordable costs by using small amounts of expensive fibrin glue in areas that are technically difficult to access and where equipment is inefficient, and using less expensive methods in areas that are easily accessible.

The method is carried out in the following manner.

[0044] The patient diagnosed with bleeding from esophageal varices in the case of portal hypertension caused by liver cirrhosis is fitted with a Sengstaken-Blakemore nasogastric tube, the stomach is washed for 10-15 min by introducing 1-2 L of water at a temperature of 10-12°C, then after 24 hours the said tube is removed, after which with the help of an endoscope at the level of the esophageal-gastric junction a fibrin adhesive is injected into the fundic gastric varices in the retrograde and anterograde direction, which includes two components, which are introduced separately with their mixing into the lumen of the vessel, namely the first component includes a fibrinogen solution, and the second component includes a mixture of thrombin solutions with 10% albumin solution, aprotinin and Ca+2 chloride, in the following ratio of components, per 1 ml:

Fibrinogen (mg) 15...45

[0046] thrombin (IU) 25...100

[0047] 10% albumin solution (ml) 10...20

[0048] aprotinin (KIU) 250...1000

[0049] Ca+2 chloride (µmol) 15...30,

[0050] The endoscope with the elastic band application device is then inserted into the esophagus and the esophageal varices are ligated with elastic bands.

[0051] The fibrinogen solution is drawn into a syringe, the other components in combination - into another syringe, which is injected separately through a trifurcated catheter at the proximal end. Inside the catheter both components combine, initiating the polymerization process with the formation of a gel-like compound, and inside the varicose vein the completion of the polymerization process with the formation of a stable fibrin clot well fixed to the vascular wall, which occludes the lumen of the vessel with the achievement of effective hemostasis.

The claimed method was used in 95 patients with liver cirrhosis and portal hypertension with variceal bleeding.

[0053] Examples of embodiments of the invention.

Example 1

[0055] Patient F., 58 years old, hospitalized in the surgery department with the diagnosis: Decompensated liver cirrhosis Child C (10) of viral etiology HBV and HCV. Portal hypertension. Gastroesophageal varices gr. III-IV. Profuse hemorrhage from esophageal varices. At fibroesophagogastroscopy, the presence of esophageal varices gr. III-IV with active jet hemorrhage with a 0.3 cm rupture, Forrest Ia, in the lower 1/3 of the esophagus and the presence of varices grade III-IV in the fundal region of the stomach without hemorrhage were determined. The claimed treatment method was performed with the installation of the Sengstaken-Blakemore nasogastric tube, the stomach was lavaged for 15 min by introducing 2 L of water with a temperature of 10...12°C, then after 24 hours the tube was removed, after which with the help of the endoscope at the level of the esophageal-gastric junction a fibrin adhesive was injected into the fundic gastric varices in the retrograde and anterograde direction, which includes two components, which was introduced separately with their mixing into the lumen of the vessel, namely the first component includes a fibrinogen solution, and the second component includes a mixture of thrombin solutions with 10% albumin solution, aprotinin and Ca+2 chloride in the claimed quantitative ratio, then the endoscope was introduced with a device for applying elastic bands into the esophagus and the esophageal varices were ligated with elastic bands. After injection, the formation of a hard and stable fibrin clot was achieved and well fixed in the variceal lumen with complete filling of the variceal lumen and hemostasis by ligation of the esophageal varices. Discharged after 8 days in satisfactory condition.

Example 2

[0057] Patient D., 32 years old, hospitalized in the surgery department with the diagnosis: Decompensated liver cirrhosis Child C (10) of HCV viral etiology. Profuse variceal hemorrhage. Hemorrhagic shock gr. II. At fibroesophagogastroscopy the presence of esophageal varices of gr. III-IV in the lower 1/3 of the esophagus, and the presence of varices of degree III-IV in the fundal region of the stomach without hemorrhage were determined. Varicose veins of the antero-medial wall with a rupture of 0.2 cm with jet hemorrhage, Forrest Ia. Endoscopic hemostasis was performed with the installation of the Sengstaken-Blakemore nasogastric tube, the stomach was lavaged for 15 min by introducing 2 L of water with a temperature of 10...12°C, then after 24 hours the tube was removed, after which with the help of the endoscope at the level of the esophageal-gastric junction a fibrin adhesive was injected into the fundic gastric varices in the retrograde and anterograde direction, which includes two components, which was introduced separately with their mixing into the lumen of the vessel, namely the first component includes a fibrinogen solution, and the second component includes a mixture of thrombin solutions with 10% albumin solution, aprotinin and Ca+2 chloride in the claimed quantitative ratio, then the endoscope was introduced with a device for applying elastic bands into the esophagus and the esophageal varices were ligated with elastic bands. After injection, the formation of a hard and stable fibrin clot was achieved and well fixed in the variceal lumen with complete filling of the variceal lumen and hemostasis by ligation of the esophageal varices. Discharged after 7 days in satisfactory condition.

1. Paquet K.J., Kuhn R., Prophylactic Endoscopic sclerotherapy in Patients with Liver Cirrhosis, Portal Hypertension and Esophageal Varices, Hepato-Gastroenterology, vol. 44, 1997, p. 625-636,

[0059] 2. AT 359652 B 1980.11.25

[0060] 3. Yoshida H., Mamada Y., Taniai N., Yamomoto K., Kawano Y., Mizuguchi Y., et al., A randomized control trial of bi-monthly versus bi-weekly endoscopic variceal ligation of esophageal varices. I have. J., Gastroenterol, 2005, vol. 100, p. 2005-2009,

[0061] 4. MD 2328 F1 2003.12.31

Claims (1)

1. Method of endoscopic hemostasis of variceal hemorrhages in liver cirrhosis, which consists in installing the Sengstaken-Blakemore nasogastric tube, performing gastric lavage for 10…15 min by introducing 1…2 L of water with a temperature of 10…12°C, then after 24 hours the aforementioned tube is removed, after which with the help of the endoscope at the level of the esophageal-gastric junction a fibrin adhesive is injected into the fundic gastric varices in the retrograde and anterograde direction, which includes two components, which are introduced separately with their mixing into the lumen of the vessel, namely the first component includes a fibrinogen solution, and the second component includes a mixture of thrombin solutions with 10% albumin solution, aprotinin and Ca+2 chloride, in the following ratio of components, per 1 ml: fibrinogen (mg) 15...45 thrombin (IU) 25...100 10% albumin solution (ml) 10...20 aprotinin (KIU) 250...1000 Ca+2 chloride (µmol) 15...30, then the endoscope with the elastic band application device is inserted into the esophagus and the esophageal varices are ligated with elastic bands.