Method of treating endogenous intoxication syndrome caused by hyperproteolysis

FIELD: medicine.

SUBSTANCE: antiproteolytic preparation Ambene in a dose of 50-250 mg is introduced intravenously by the stream infusion for at least three days every 3-4 hours in a combination with heparin. Heparin is introduced subcutaneously is a dose of 250 units 4 times a day.

EFFECT: effective treatment of endogenous intoxication syndrome caused by proteolysis by blocking fibrinolysis and enhancing the detoxifying and anti-inflammatory action of Ambene.

2 tbl, 2 ex

 

The invention relates to medicine, in particular to toxicology, and can be used for the treatment of syndrome of endogenous intoxication caused by hyperpreterism in the case of acute poisoning caused by neurotropic substances steps.

Known in vitro methods (hemosorption, limfosorbtsiya, hemofiltration, plasmapheresis) edema of endogenous intoxication in acute poisoning with sorbents (Lopatkin N.A., Lopukhin, Y.M. Efferent methods in medicine : theoretical and clinical aspects of in vitro treatment methods). - M.: Medicine, 1989. - 352). Their disadvantages are the possible adsorption of oxygen getting into the blood particles sorbents, activation of blood coagulation and fibrinolysis.

The physico-chemical ways to treat endogenous intoxication applied transcranial electrical stimulation (mesodiencephalic modulation), ultraviolet blood irradiation (Luzhniki E.A., Goldfarb US Physiogeography acute poisoning. - M.: Malpractice-M, 2002. 200 C.).

Their disadvantages are the complexity, low efficiency, the need for additional equipment.

As pharmacological methods of treatment of endogenous intoxication apply sodium hypochlorite, antioxidants (tocopherol), Immunostimulants (T-activin). To fault the m treatment with sodium hypochlorite include its ability, as a strong oxidant injury of blood corpuscles, the disadvantages of tocopherol, T-activin - a low efficiency.

Closest to the claimed is a method of treatment of endogenous intoxication caused by hyperpreterism, by applying a natural inhibitor of fibrinolysis kontrikala (Aprotinin), (Sitkovskiy NB, Hanes G.S., Kutsenko T.A. proteolysis Inhibitors in pediatric surgery. - Kiev: Health, 1977. - 87 S.).

The disadvantage of this method, selected as a prototype, is alien to the body kontrikala as antigen, the ability to cause allergic reactions need to use large doses and prolonged administration to obtain the desired clinical effect.

Other prototype disadvantages are its high cost, complexity of industrial production and purification of the drug.

The present invention is to increase the effectiveness of treatment of endogenous intoxication caused by hyperpreterism, and cheaper treatment method.

According to the invention, the problem is solved in that in the method of treating syndrome of endogenous intoxication caused by hyperpreterism, including standard detoxification therapy antiproteolytic drugs, as antiproteolytic drug use is comfort ambien, which is injected intravenous bolus at a dose of from 50 to 250 mg for at least three days with an interval of 3-4 hours in combination with subcutaneous injection of heparin.

Ambien inhibits proteolytic process by blocking plasminogen activators and inhibiting the action of plasmin. It inhibits fibrinolysis, competitive saturating lessinvasive receptors, through which the plasminogen (plasmin) is associated with fibrinogen (fibrin), which leads to more effective treatment of endotoxemia, and also inhibits the formation of biogenic peptide complexes that can influence the exudative phase of inflammation. Ambien improves blood rheology, has a beneficial effect on circulation in the damaged tissues, preventing the development of hypoxia.

Amben is a domestic product, it is easy to obtain. Compared to the equally effective doses kontrikala, ambien 100 times cheaper. The economic effect of the application of ambana obvious.

This action ambien has a dose of from 50 to 250 mg. Doses less than 50 mg does not cause the desired effect, whereas the introduction in doses exceeding 250 mg can cause side effects.

The combined introduction of heparin enhances the detoxifying and anti-inflammatory effect of Albena. Heparin as an activator of anti-thrombin III, blocks the action of thrombin, etc the other vitamin K-dependent proteases of the coagulation cascade, reduces platelet aggregation. Anti-inflammatory effect of heparin is associated with improvement of microcirculation in inflammation due to suppression of intravascular thrombosis, inhibition of chemotaxis of neutrophils, reduce their adhesion to the endothelium and other

The claimed frequency regime and the introduction of Albena and heparin due to their pharmacokinetic characteristics. Therapeutic concentration amben is created in the blood when a single-step introduction. When administered intravenously, the maximum concentration of drug in the blood is determined immediately after administration and lasts up to 3 hours followed by a decline to 4 th hour. Therefore, the time interval between the introduction of this drug should not exceed 4 hours.

The duration of drug injection (not less than three days) is related to the fact that in the early toxicogenic phase (first, second, third days after acute poisoning, when the venom is in the bloodstream) contents of oligopeptides as markers, reflecting the level of endogenous intoxication, reaches its maximum (especially in the first day). Ambien promotes the redistribution of markers of endotoxemia in the direction of reducing their content in erythrocyte membranes, accumulation in the plasma and their subsequent excretion in the urine.

The concentration of oligopeptides in the blood correlates with the degree is to prolong activation of fibrinolysis. The introduction of inhibitors of proteolysis, in particular amben, reduces severity of endogenous intoxication.

According to scientific-technical and patent literature, the use of amben in combination with heparin for the treatment of endogenous intoxication in acute poisoning in medicine is unknown. Therefore, the claimed invention meets the criterion of "significant differences".

The method is as follows. The patient with acute poisoning neurotropic substance intravenous bolus injected ambien in a dose of from 50 to 250 mg every 3-4 hours for at least 3 days in combination with subcutaneous injection of heparin.

Example 1.

Patient M., 38 years old was admitted to the Department for the treatment of acute poisoning with a diagnosis of acute poisoning substance neurotropic action (azaleptin) severe. Diagnosis of chemical-Toxicological investigation of biological media. The exposure time is longer than 6 hours. When entering a serious condition, consciousness at the level of coma I-II century Skin pale, mydriasis, respiratory rate of 25 per minute, heart rate of 115 beats per minute, blood pressure of 90 mm and 60 mm Hg heart sounds deaf. Abdomen palpation soft.

The patient was obtained by infusion of glucose, saline, poliglyukina, lasiks, prednisolone, dopamine. Conducted hemosorption. In the future priest who drank to intravenous introduction of Albena in the form of a 1% solution of 15 ml (150 mg) every 4 hours. In combination with ambeno was subcutaneously injected heparin 2500 UNITS 4 times a day. Assessed the level of consciousness on a scale Glasgow, hemodynamics, additional indicators of the level of oligopeptides in plasma and erythrocytes at admission of the patient, on the 1st, 3rd and 5th day. On the 1st day was marked improvement in the level of consciousness to spoor - somnolence (9-11 points on the scale of Glasgow). By the end of the first day there was a decrease in the concentration of oligopeptides on erythrocytes in 2 times to 0.31 g/l (0.74 g/l at admission), but simultaneously increased their content in plasma and urine compared with baseline at the time of hospitalization. This coincided with the beginning of stabilization of the main clinical indicators - consciousness and hemodynamics. Discharged after cupping intoxication on the 5th day after the poisoning.

Example 2.

Patient K., 46 years old, was admitted to the Department for the treatment of acute poisoning with a diagnosis of acute poisoning substance neurotropic action (phenazepam) severe. Diagnosis of chemical-Toxicological investigation of biological media. The exposure time of more than 12 hours. When entering a serious condition, consciousness level spoor coma I tbsp. Skin pale, dry, respiratory rate 16 per minute, pulse 96 beats per minute, blood pressure of 110 mm and 60 mm Hg heart sounds deaf. Conducted cured the e: glucose, poliglyukina, lasiks, prednisolone, dopamine, amben. Ambien was injected intravenously 10 ml 1% solution (100 mg) every 4 hours, heparin 2500 UNITS subcutaneously 4 times a day. On the first day was marked improvement in the level of consciousness to somnolencia (11-12 points on the scale of Glasgow), to the end of the first day was observed at 1.5 times the decrease in the concentration of oligopeptides on the erythrocytes to 0.33 g/l (0.54 g/l at admission). Discharged after cupping intoxication on the day 3 after poisoning.

Lower content of oligopeptides in the plasma of patients treated with ambeno, remained until 5 days of observation. Especially pronounced difference is observed for the 3-day hospital stay.

Presented in the tables, the results of clinical studies conducted in experimental (20 patients) and control group (10 patients), show a positive effect of the proposed method.

Table 1
The influence of Albena on the dynamics of the clinical course of intoxication
IndexThe time from receipt of the patient in the office
1 h 1 day3 day5 day
Control, n=10The monitoring group, amben n=20Control, n=10The monitoring group, amben n=20Control, n=10The monitoring group, amben n=20Control, n=10The monitoring group, amben n=20
Recovery of consciousness (number of patients)00311818919
Stabilization of hemodynamics (number of patients)00149919919

Table 2
Dynamics of the content of oligopeptides (g/l) in RosNOU blood (M±n) in patients with acute severe poisoning
The study periodThe concentration of oligopeptides, g/l
Control (n=10)Amben (n=50)
Plasma
When receiving0,765±0,0290,67±0,04
1 day0,966±0,0170,84±0,03*
3 daydetermined as 0.720±to 0.1080,37±0,03*
5 day0,360±0,0270,28±0,01*
Erythrocytes
When receiving0,822±0,0300,74±0,05
1 day0,966±0,0170,311±0,08*
3 day0,568±0,0490,321±0,030*
5 dayin 0.288±0,0210,270±0,016
Note the: * - the difference with the control was statistically significant (p<0,05).

The proposed treatment method carried out in 50 patients with acute poisoning.

The inventive method improves the clinical course of acute poisoning, reduces or eliminates the expression of endogenous intoxication, which allows survival of the patients in serious condition, shortens hospital stay.

Ambien as a product of domestic production is easy to obtain and manufacture. Compared to the equally effective doses of a natural inhibitor of fibrinolysis kontrikala amben 100 times cheaper, than its obvious economic benefits.

A method of treating syndrome of endogenous intoxication caused by hyperpreterism, including standard detoxification therapy antiproteolytic preparations, characterized in that as antiproteolytic of the drug to enter amben dose of 50-250 mg intravenous bolus over at least three days with an interval of 3-4 hours and additionally introducing heparin subcutaneously at a dose of 250 IU 4 times a day.



 

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