RU2141315C1 - Method of thrombolytic therapy - Google Patents

Abstract

FIELD: medicine, vascular surgery. SUBSTANCE: method involves administration of the curative mixture consisting of heparin, hydrocortisone, chymotrypsin, ampicillin and novocaine solution (two or three injections) into paravasal tissue of thrombus-containing segment. Intrathrombotic infusion of rheopolyglucin-celiase-heparin mixture is performed by continuous intravenous catheterization of posteriotibia vein. Invention can be used for treatment of leofemoral venous thrombosis and provides the uniform distribution of thermobolytic agent in the zone of thrombotic process. EFFECT: enhanced effectiveness of thrombolytic therapy, improved regional hemodynamics, decreased hospitalization period, decreased complications and lethality. 1 dwg

Description

 The invention relates to medicine and will find application in vascular surgery in the treatment of patients with acute descending thrombosis of the main veins of the lower extremities with a disease duration of no more than 3-5 days.

 Conducted research on patent and medical literature revealed a number of methods of thrombolytic therapy of acute venous thrombosis, depending on the method and place of administration of the drug.

 The most famous and widely used method is the fractional introduction of thrombolytics (fibrinolysin, streptase, steptokinase, urokinase, etc.) into the general bloodstream / Malinovsky N.N. et al., 1976; Danilova L.M. et al., 1981; Chazov E.I. et al., 1981: Andreenko G.V., 1982; Matskov A.S. et al. 1983; Zhalnerauskane et al., 1984; Tsybyrne K.A. et al., 1985 and others. The disadvantage of this method of thrombolytic therapy is the low concentration of thrombolytic in the area of thrombosis, the threat of allergic and hemorrhagic complications, sharp fluctuations in the concentration of the drug in connection with its fractional administration.

 Given the shortcomings of the introduction of thrombolytics into the general bloodstream Askerkhanov R. P. / 1973 /, Mamelov Yu.I., et al. / 1983 /, Smirnov V.E. et al. / 1984 / and others apply the method of regional infusion of fibrinolytics into the saphenous vein of the foot. Although this technique allows you to slightly increase the concentration of the drug in the thrombosis zone, it is not enough due to the low diffusion of plasminogen activators into the thickness of the thrombotic masses and the small area of contact between the drug and the thrombus. This explains the fact that the active processes of lysis are observed only in the peripheral parts of the thrombus, without involving its central sections in this process / Savelyev VS, 1971; Gireyev G.I. et al. 1989 g.

 In order to evenly distribute thrombolytic in the area of the thrombolytic process with common venous thrombosis, Alekseev P.P. et al. / 1972 /, Gervaziev V.V. et al. / 1988 / apply arterial infusion of thrombolytics. The disadvantage of this method is the impossibility of continuous administration of drugs into the arterial bed / the danger of hematoma formation, bleeding /, which makes such therapy ineffective.

 Askerkhanov R.P. et al. / 1983 /, Gireev G.I. et al. / 1989 / in order to activate endogenous thrombolysis in acute venous thrombosis, the method of paravasal instillation of a treatment mixture consisting of heparin, hydrocortisone, antibiotic and novocaine is successfully used. The method is simple and technically simple. Along with positive qualities, the method has some disadvantages, including inefficiency with common lesions of the venous system.

 The basic object selected as a prototype is the thrombolytic therapy method described by V.D. Kargin et al. / 1990 /. The authors use regional infusion of thrombolytic renokinase, a new domestic fibrinolytic drug developed at the Leningrad Research Institute of Hematology and Blood Transfusion / ed. testimonial. N 147934 /. On average, the initial daily dose of the drug is 1000 fibrinolytic units per 1 kg of patient weight. Half of the indicated amount was administered intravenously for 30 minutes, and the rest was infused for 2 hours. Infusions were carried out through a catheter inserted into the internal marginal vein of the foot. At the end of the thrombolytic drug infusion, they switched to an intravenous infusion of a heparin solution / 30/50 thousand units. per day/. Repeated administration of renokinase was carried out on the 2-3rd day based on the daily dose of the drug with a total course dose of 180-240 thousand units. renokinase with a patient body weight of 60-80 kg. A day after the last administration of the drug, they switched to subcutaneous injections of heparin, and after 5-6 days, they received indirect anticoagulants, which lasted up to 3 months on an outpatient basis.

 The disadvantages of the prototype method are, firstly, the insufficient concentration of thrombolytic in the deep venous network due to its "leaching" in the conditions of venous hypertension through the expanded subcutaneous venous network; secondly, the small area of the active zones of contact of the drug with a thrombus; thirdly, low diffusion of the plasminogen activator / renokinase / into the thickness of the thrombotic masses, especially with common lesions; fourthly, an unstable adequate concentration of thrombolytic in the bloodstream associated with fractional administration of the drug.

 The aim of the present invention is to develop an effective method for local thrombolytic therapy of acute descending ileofemoral venous thrombosis, which allows lysing thrombotic masses in the early stages (up to 2 days) with restoration of main blood flow, in later ones improving regional hemodynamics due to partial thrombolysis and early recanalization, and relieving inflammation venous wall, improve microcirculation, reduce the processes of sclerosis and death of the valvular apparatus.

 This goal is achieved by continuous intravenous intrathrombotic infusion of reopoliglyukin-celiasis / streptase, renokinase / heparin mixture in combination with two-threefold blockades of the treatment mixture / hydrocortisone, heparin, ampicillin, novocaine, imotripsin.

 Indications for the proposed treatment were patients with occlusive forms of acute ileofemoral venous thrombosis with a central pathway for the development of thrombotic occlusion / descending thrombosis / with a disease duration of no more than 3-5 days.

 The method is schematically depicted in the drawing, where: a) inferior vena cava; b) common iliac vein; c) external iliac vein; d) femoral vein; e) posterior tibial vein; e) thrombotic masses; g) therapeutic mixture in paravasal tissue; h) umbrella filter.

The method is as follows:
Upon admission to patients, a general clinical examination, a general coagulogram, thromboelastography, rheovasography, and ultrasound dopplerography are urgently performed. To clarify the localization of the upper level of the thrombus by means of catheterization of the inferior vena cava (a), retrograde ileocavagography is performed. In cases of transition of the thrombotic process to the inferior vena cava (a), an umbilical cavafilter is implanted, distal venography is performed through the posterior tibial vein (e) by means of an intravenous or subclavian catheter.

 After clarification of the prevalence and localization of thrombotic masses (a) through the posterior tibial vein (e), an vinyl chloride / ureter / microcalculator with lateral openings is introduced antegrade / under the control of an X-ray television installation / through thrombotic masses (e) so that its end is 5-10 cm below the upper end of the thrombus / Fig. 1/. The wound on the foot is sutured, all vessels are carefully ligated.

 Two or three times / depending on the age and prevalence of the thrombotic process / from the inguinal and popliteal region of the affected limb using long needles into the paravasal tissue of the thrombosed main veins, a therapeutic mixture is introduced consisting of heparin / 5000 units /, hydrocortisone / 50 units / chymotrypsin / 10 mg /, ampicillin / 0.5 / and 0.25% solution of novocaine / 200.0 / / Auth. testimonial. N 1197647 /.

 Using a drug dispenser / DLV-1 /, a reopoliglyukin-celase-heparin mixture / 15 ml, 40,000 units is continuously injected into the catheter for 2 days. and 300 units. per 1 kg of weight per day, respectively. On the 3rd day, thrombolytics are canceled, and the reopoliglyukin-heparin mixture in the same dosages continues to be introduced into the catheter. On day 4, the catheter is removed. The dose of heparin is gradually reduced with the passage of 7-8 days to indirect anticoagulants, which in turn are canceled in a similar way on 15-18 days. In the future, patients are prescribed for 3 months tiklid up to 1 tab. 3 times a day.

 In addition to the above drugs, the patient is prescribed a complex of treatment: nicotinic acid, trental, aspirin, diphenhydramine, troxevasin, broad-spectrum antibiotics.

 The method was developed on 15 outbred dogs. The phlebothrombosis model was created by the Arthus passive reaction method in an isolated segment of the femoral vein (auth. Certificate N 1727156). Local thrombolytic therapy was carried out in terms of 1, 3, 5, 7, 10 days after modeling venous thrombosis / 3 experiments in each term of the experiment /.

 Complete lysis of the thrombus with restoration of the main blood flow occurred in 5 experiments / in 3 experiments with daily thrombosis and in 2 experiments with 3-day thrombosis / Fig. 1/. Partial thrombolysis was noted in 3 cases / in 1 experiment with 3 daily thrombosis and 2 experiments with 5-day thrombosis /. In other experiments, the phlebographic picture was unchanged.

 The method was tested in a clinic for 13 patients with acute ileofemoral venous thrombosis in the early stages of the disease. The results of the treatment confirm the high efficiency of the developed method. In 4 patients there was complete thrombolysis with restoration of the main hemorrhage, in 7 patients partial thrombolysis with a significant improvement in regional blood flow, in 2 patients a decrease in the extent of thrombotic masses was not observed. No complications were noted.

 As shown by experimental studies and observations in the clinic, the proposed method of local thrombotic therapy, in comparison with the prototype method, improves the results of treatment of acute ileofemoral venous thrombosis, allows the use of thrombotic masses with restoration of the main blood flow up to 48 hours of disease duration in 80% of patients, reduces the duration of the patient’s stay in the hospital by 3.1 ± 0.4 days, reduces the number of complications and mortality.

 Example 1. Patient M., 27 years old / East. bol. 12/16722 / was admitted to the hospital on 12.10.91, with a diagnosis of acute ileofemoral venous thrombosis on the left. Sick about a day. The disease associates with the flu suffered the day before.

 Upon receipt of a complaint of pain in the lumbar region, blueness and swelling of the limb. Objectively: pathology from the internal organs was not detected. Locally: the left lower limb is sharply swollen, with a bluish tinge, tense, painful along the main vessels. Ripple in the arteries of the limbs is weakened.

 The patient urgently performed laboratory tests of blood, urine, coagulogram. An ascending phlebography of the deep veins of the lower leg, thigh, and pelvis was performed through a catheterized posterior tibial vein. According to the Seldinger method, retrograde ileocavagraphy was performed through the femoral vein of the opposite limb. An angiographic study revealed the presence of acute descending iliac-femoral venous thrombosis on the left / Fig. 1/.

 After angiographic examination, the catheter in the posterior tibial vein to the ureteric was performed through the entire thickness of the thrombotic mass according to the method proposed above. 3 hours after venography, a reopoliglyukin-celiasis-heparin mixture / 1200 ml, 3 mln units was continuously introduced through the installed catheter for 48 hours. and 20,000 units. per day, respectively. On the 3rd day, the administration of thrombolytic was stopped, and the reopoliglyukin-heparin mixture / 1200 ml and 30,000 units were continued to be continuously introduced into the catheter. per day, respectively. On day 4, the catheter was removed. The dose of heparin was gradually reduced with the transition to Finilin on day 8, which in turn was canceled on day 15 of treatment. Subsequently, for 3 months, the patient received tiklid 1 tab. 3 times a day.

 On days 1 and 3 from the start of treatment, a treatment mixture consisting of hydrocortisone / 50 units /, heparin / 5000 units /, ampicillin / was injected into the paravasal tissue of the affected trunk vein using long needles from the inguinal and popliteal areas in the distal and proximal directions 0.5 /, chymotrypsin / 10 kg / and 150.0 0.25% solution of novocaine.

 In addition to the above drugs, the complex of treatment includes: nicotinic acid, trental, aspirin, diphenhydramine, troxevasin, gentamicin.

 From the first day of treatment, the phenomena of venous insufficiency progressively decreased. At 8 days, limb edema was not determined. On day 15 control phlebography was performed. Phlebograms show thromlosis with restoration of the main blood flow. The patient was discharged on 01.30.91.

 After 8 months / 09/23/91, the patient was re-examined. No complaints. Clinical phenomena of chronic venous insufficiency have not been identified. On rheovasography and ultrasound doplegraphy, venous blood flow is not impaired.

Features
1. A thrombolytic drug is injected into the thrombotic mass through catheterization of the posterior tibial vein.

 2. The infusion of thrombolytic is carried out continuously using a drug dispenser / DLV-1 /.

 3. Two or three times / depending on the duration of the disease and the effect of the therapy / patients undergo paravasal instillation of the treatment mixture, consisting of hydrocortisone, heparin, ampicillin, chymotrypsin / trypsin / and novocaine.

Compared with existing methods of thrombolytic therapy, the method has the following advantages:
1. Significantly increases the concentration and contact area of thrombolytic drugs in the area of thrombotic occlusion, which allows the method to be used for common forms of the disease.

 2. Paral instillations of the treatment mixture interrupt the inflammatory process and the processes of sclerosis in the paravenous tissue and venous wall, improve local microcirculation and thereby trophic venous wall, reduce the effect of autosensitization, activate fibrinolytic factors / plasminogen activator /, embedded in the venous wall.

 3. The use of continuous intravenous intrathrombotic infusion of reopoliglyukin-celiasis / streptase renokinase / heparin mixture in combination with paravasal instillations of the treatment mixture activates exo- and endogenous thrombolysis, which improves the results of thrombolytic therapy and achieves complete thrombolysis within the period of up to 48 hours of the onset of the disease 80% of patients at a later date / 3-5 days / achieve partial thrombolysis and recanalization with a significant restoration of regional hemodynamics, Socra it terms of hospitalization of patients on 3,1 ± 0,4 days, to reduce the number of complications and mortality.

 The method was developed on experimental animals and tested on the basis of the Department of Surgical Diseases No. 2 of the Dagestan Medical Institute.

Sources of information taken into account:
1. Kargin V.D., Vedensky A.N., Sabelnikov V.V. et al. - Bulletin of Surgery. I.I. Grekova, 1990, N 11, p. 20-24 - prototype.

 2. Alekseev P.P., Dyachenko M.Ya., Bagdasaryan V.S. and others. - In the book. Infusion therapy in surgery. Barnaul, 1972, p. 220-223.

 3. Andreyenko G.V. - In the book: Enzymology of thrombolysis and streptokinase. Minsk, 1982, p. 127-134.

 4. Askerkhanov R.P. - Surgery of peripheral veins. Makhachkala, 1973, p. 311.

 5. Askerkhanov R.P., Zakariev Z.M. - J. Clinical Surgery, 1983, N 7, p. 58-60.

 6. Askerkhanov R.P., Zakariev E.M., Askerkhanov G.R. - A method for the treatment of acute local thrombophlebitis. Auth. testimonial. N 11197647, 1985.

 7. Gervaziev V. B., Chernenko V. F., Karpenko A. A. et al. - In the book: Diagnosis and treatment of peripheral vascular diseases. Tomsk, 1988, p. 3-7.

 8. Gireyev G.I., Askerkhanov G.R., Zakariyev Z.M. - J. Herald of Surgery, N 6, 1989 p. 124.

 9. Danilova L.M., Shestakova V.A., Ilyin V.N. -Problems of hematology and blood transfusion, 1981, v. 26, No. 3, p. 12-15.

 10. Zhalnerauskene I., Sirvidis V. Trponis V. et al. - In the book: Actual. noncommunicable disease prevention issues. Vilnius, 1984, p. 137-138.

 11. Malinovsky N.N., Kozlov V.A. - Anticoagulant and thrombolytic therapy in surgery. M. Medicine. 1976, p. 423.

 12. Mamelov Yu. I., Zaporizhsky A.S. - In: Vascular Surgery, Maykop, 1983, p. 152-155.

 13. Matskiv A.S., Ogonovsky V.K. - In the book: Acute pathology of the great vessels. Thes. doc. Kiev, 1983, p. 108-109.

 14. Savelyev V.S. - Abstracts of the 10th International Congress on Cardiovascular Diseases. M. 1971, p. 178-179.

 15. Smirnov V.E. Vartanov I.E., Lavreshin P.M. - In the book: Actual. practical health issues. Stavropol, 1984, p. 103.

 16. Chasov E.I., Mazaev A.V., et al. J. Therapeutic Art, 1981, v. 53, No. 9, p. 79-84.

 17. Tsybyrne K.A., Thunderstorm S.V. - In the book: Actual. issues of emergency vascular surgery. All Conf., Minsk, 1985 from 101-102.

Claims (1)

 A method of thrombolytic therapy of acute ileofemoral venous thrombosis by regional intravenous infusion of thrombolytic drugs, characterized in that by means of a microirrigator introduced through the posterior tibial vein, an intrathrombotic infusion of reopoliglyukin (rheomacrodex, reoglumantum), a mixture of three-primal streptaria, streptaria, protharaptinum streptosa, paravasal tissue of the affected trunk vein is injected with a treatment mixture consisting of hydrocortisone, heparin, chymotrypsin, ampic Llyn and novocaine.