RU2489172C1 - Method of therapeutic discrete plasmapheresis with extracorporeal erythroxyte and leukocyte modification with interferon inducers, antioxidants and cell protectors - Google Patents

Abstract

FIELD: medicine.

SUBSTANCE: invention refers to immunology, transfusion medicine and intensive therapy, and may be used to treat endotoxemias of various aethiologies. That is ensured by blood sampling, centrifuging to plasma and erythrocyte-leukocyte mass. The leukocyte suspension is added with interferon inducers, hepatoprotectors and antioxidants in sub-therapeutic doses. The leukocyte suspension is incubated at t - 37°C for 120 min, and then introduced into the patient's venous bed. The erythrocyte mass is added with cerebroprotectors, hepatoprotectors and antioxidants in sub-therapeutic doses. The erythrocyte mass is incubated at t - 37°C for 45 min, and then introduced into the patient's venous bed. With no contraindications, the second session of each cycle involves the exposure to ultrasound (ultraviolet irradiation 150 J) preceding the incubation of the leukocyte suspension with the added therapeutic preparations. The length of treatment makes three 5-session cycles in average every 2 days as recommended. The length of each session is min. 3.5 hours and max. 4.5 hours. The 1st and 2^nd cycles are separated by 2 weeks, while the 2^nd and 3^rd ones - by 4 weeks. The total therapeutic course makes 2-3 months.

EFFECT: method provides the fast recovery of quality of life in the patients suffering endotoxemias due to the optimal selection of the centrifugation parameters, incubation regimens and optimal ultrasound power.

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Description

 The invention relates to medicine, namely to efferent therapy, immunology, transfusiology and intensive care, and can be used in the treatment of endotoxemia of various etiologies.

There is a known method of therapeutic plasmapheresis, in which the blood received from a patient is centrifuged in a system of plastic containers, while detoxifying - removing the patient's toxic plasma, replacement alloplasmotransfusion and autotransfusion of erythrocyte and leukocyte suspensions, followed by return to the venous channel. The disadvantage of this method is that the red blood cells are returned to the patient unchanged, while the activity of their antioxidant enzymes remains low, which reduces the clinical effectiveness of therapeutic plasmapheresis.

To increase clinical efficacy, an ultraviolet suspension of leukocyte suspension is carried out, as a result of which biologically active substances (lipid peroxidation products) are formed, which activate antioxidant erythrocyte enzymes by the feedback mechanism and to restore the sensitivity of leukocytes to interferon inducers from the second session in the absence of contraindications.

Employees of the Central Research Institute of Tuberculosis of the Russian Academy of Medical Sciences in 1995 began to use the first modification of blood cells with drugs for hemapheresis. For respiratory diseases, which are based on the immunopathological syndrome, the methods of lymphocytopheresis and extracorporeal modification of lymphocytes with prednisolone were used, which made it possible to achieve the effect of pulse therapy with corticosteroids when used in small doses without dangerous side effects (Shmelev E.I., Stepanyan I.E. Methods of hemapheresis in pulmonological practice.Materials of the first conference of the Moscow Society of hemapheresis. M., 1993. P.163-170; Stepanyan I.E., Ozerova L.V., Shmelev E.I. nyh alveolitis using gemafereza. Pulmonology. 1993. №3. S.15-19).

As is known, the therapeutic effect of corticosteroids in this case is based on their ability to suppress the pathological component of immunity, namely, a decrease in the functional activity of T-lymphocytes and a suppression of the synthesis of pro-inflammatory cytokines.

With the advent of highly effective interferon inducers, primarily cycloferon, we were able to act on non-specific immunity, that is, on the interferon system, stimulating its cellular production.

The most important thing is that during the induction of interferon its two types are synthesized, which have video tissue specificity, and it is the use of a complex of interferons of a given specificity, rather than individual peptides, that makes it possible to correct pathological processes. In vivo production, that is, “inside a living organism” or “inside a cell” is due to the presence of sensitive cell systems capable of synthesizing interferons (IFN) in response to a particular inducer, and the ability of producer cells to “meet” with the inducer. Like any biological process, the synthesis of IFN is subject to regulation: after the induction and production of IFN, its synthesis is rapidly activated, which entails a phase of refractoriness - hyporeactivity, which is noted when the homologous inducer is reintroduced into the body and is expressed in the suppression (inhibition) of cell ability synthesize IFN. The decrease in the production of IFN is accompanied by the accumulation in the serum of a hyporeactivity factor - repressor translation, which performs the control functions of IFN synthesis. Thus, the process of IFN induction “includes” opposite mechanisms: the accumulation of IFN-RNA-IFN (informational interferon ribonucleic acid, that is, the basis for the synthesis of interferon molecules) and activation of the translation repressor synthesis [3, 4]. The synthesized repressor inactivates IFN-RNA, causing a state of hyporeactivity in the cells to re-induction IFN by a homologous inducer.

The accumulation of i-RNA of the repressor is somewhat ahead of the accumulation of i-RNA-IFN, this is because the repressor needs a certain amount of time to synthesize and carry out its control and regulatory functions. The hyporeactivity factor controls the synthesis of IFN at the level of translation. The mechanism of action of the translation repressor is different from the action of IFN. The repressor of IFN products, unlike IFN, does not have antiviral activity. The repressor synthetically binds IFN-RNA-IFN. Moreover, the repressor does not affect the antiviral effect of IFN. On the other hand, a repressor, like IFN, has species specificity, this is confirmed by the fact that IFN synthesis is not carried out if i-RNA-IFN is translated in homologous hyporeactive cells. The introduction of i-RNA into hyporeactive cells stimulates the full synthesis of IFN.

Ultimately, interferonogenesis consists of several stages (induction-production-action-effects) and presents a kind of chain reaction in response to an alarm (various diseases) [5-11].

Production and secretion of cytokines (IFN α / β, IL-1, TNF-α, IL-6.8) are among the earliest events associated with the interaction of microorganisms with macrophages; This early non-specific response to infection is important for several reasons: it develops very quickly because it is not associated with the need for accumulation of a clone of cells that responds to a specific antigen; however, an early cytokine response affects the subsequent specific immune response [10, 12-15].

Interferon activates macrophages and EK cells (natural killer cells or NK cells, i.e. special lymphocytes that produce-synthesize cytokines), which then synthesize γ-interferon, IL-1,2,4,6, TNF-α, as a result, macrophages and EC cells acquire the ability to lyse virus-infected cells [16, 17].

The relevance of the invention: The problem of emergency detoxification and immunocorrection in patients with infectious and autoimmune diseases, intoxications of various origins remains relevant. This is due to severe endotoxemia, progressive course, immune disorders, leading to the development of multiple organ failure. An effective method of combating endotoxemia is gravitational blood surgery - plasmapheresis. Discrete plasmapheresis is the most natural, physiological, simple, affordable, reliable and universal method that allows you to remove all substrates present in the plasma, regardless of their nature, molecular weight. The advantage of discrete plasmapheresis with EMEiL is the possibility of its use not only in large centers of efferent therapy, but also in hospitals, medical units, clinics and in "disaster medicine". Discrete plasmapheresis with EMEiL is not an isolated treatment method, but harmoniously combined with other methods of conservative therapy.

The objective of the invention: the development of a method that increases the real effectiveness of detoxification therapy in order to reduce the risk of side effects and complications in the recovery period, reduce the patient’s hospital stay and increase the duration of stable remission, reduce the amount of drugs consumed (expensive drugs and having a number of side effects for the body ), prolonging the period of quality life, reducing mortality. Technical result: The method allows to achieve a faster restoration of the patient’s quality of life, to avoid the complications associated with the prolonged use of infusion, antibacterial therapy, antiviral and detoxification therapy, improve treatment results, reduce the incidence of disability and death.

Our studies allowed us to select the parameters of centrifugation so that the volume of the obtained erythro-leukomass was the maximum; to establish optimal incubation regimes of cell mass with various groups of drugs; to fix the optimal energy of ultraviolet radiation and such doses of injected drugs that correspond to the most pronounced detoxification, immunomodulating and therapeutic effect.

The essence of the invention: Discrete plasmapheresis with EMEiL is a method of separation of blood by centrifugation on plasma with endotoxins and erythro-leukomass diluted with isotonic sodium chloride solution followed by ultraviolet irradiation of leukocyte suspension and the administration of a drug with erythrocyte mass and leukocyte suspension followed by a suspension of drugs return to the venous channel of the patient.

A method of conducting therapeutic discrete plasmapheresis with EMEiL is provided, which consists in centrifuging the blood received from a patient onto plasma and erythro-leukomass diluted with isotonic sodium chloride solution, followed by its return to the venous bed, which differs from therapeutic discrete plasmapheresis in that:

1. Interferon inducers, hepatoprotectors and antioxidants are introduced into the leukocyte suspension in doses lower than therapeutic, after which the leukocyte suspension is incubated at t - 37 ° C for 120 minutes, then the patient is returned to the venous bed;

2. Cerebroprotectors, hepatoprotectors and antioxidants are introduced into the erythrocyte mass at doses lower than therapeutic, after which the red blood mass is incubated at t - 37 ° C for 45 minutes, then the patient is returned to the venous bed;

3. From the second session of each cycle, in the absence of contraindications, before the incubation of the leukocyte suspension with the injected drugs, produce ultraviolet radiation (UV-150 J).

The duration of treatment is an average of three cycles of 5 sessions with a recommended interval of 2 days. The duration of the session is not less than 3.5 hours and not more than 4.5 hours, the interval between 1 and 2 cycles is 2 weeks, between 2 and 3-4 weeks. The general course of treatment is 2-3 months.

The implementation of the invention

Discrete plasmapheresis with extracorporeal modification of erythrocytes and leukocytes by interferon inducers, antioxidants and cell protectors (Discrete plasmapheresis with EMEiL) is a method of separation of blood by centrifugation on plasma with endotoxins and erythro-leukomass diluted with isotonic ultrafluoride with sodium chloride and into the erythrocyte mass and leukocyte suspension of drugs, followed by their incubation and sequential return into the patient’s venous bed (autotransfusion).

The use of leukocyte modification with interferon inducers can significantly increase the effectiveness of the drug due to its direct relatively long-term interaction with blood cells, which is impossible with conventional intravenous or intramuscular administration. We use leukocyte modification with interferon inducers, hepatoprotectors and antioxidants (cycloferon, heptral, ascorbic acid). This combination of drugs is most acceptable. During plasmapheresis, a leukocyte suspension (100-170 ml) is released, to which these drugs are added at doses lower than therapeutic, after which the leukocyte suspension is incubated at t - 37 ° C for 120 minutes, then returned to the patient's venous bed.

Along with this, red blood cells are modified by cerebroprotectors, hepatoprotectors, antioxidant drugs (mexidol, phosphogliv, cytoflavin). The erythrocyte mass is incubated at t - 37 ° C for 45 minutes (red blood cells have a more pronounced ability to bind drugs than white blood cells due to the greater number of receptors), then a similar return to the patient’s venous bed.

And, finally, from the second session of each cycle in the absence of contraindications before incubation of the leukocyte suspension with the injected drugs, ultraviolet irradiation (UV-150 J) is carried out.

The effectiveness of this method requires an average of three cycles. One cycle consists of 5 sessions with a recommended interval of 2 days. The duration of the session should be at least 3.5 hours, but not more than 4.5 hours.

The interval between 1 and 2 cycles is 2 weeks, between 2 and 3-4 weeks. Thus, the total maximum duration of therapy is 2-3 months.

Indications for discrete plasmapheresis by EMEiL:

1. Respiratory diseases (pneumonia, COPD, asthma, uncontrolled course);

2. Diseases of the cardiovascular system (IHD, hypertension, myocarditis, obliterating atherosclerosis of the main arteries of the extremities);

3. Digestive diseases (peptic ulcer of the stomach and duodenum, chronic hepatitis, cirrhosis of various etiologies, including alcoholic liver disease, acute pancreatitis with elements of pancreatic necrosis);

4. Purulent-inflammatory surgical diseases (infectious endocarditis, sepsis of various etiologies);

5. Kidney disease (pyelonephritis, glomerulonephritis, TIN with transformation into chronic renal failure);

6. Dermatological diseases (dermatitis, furunculosis, psoriasis, neurodermatitis, erysipelas, pyoderma);

7. Diseases of the ENT organs (abscesses of the oropharynx, boils of the ENT organs, tonsillitis, otitis media);

8. Systemic diseases of the connective tissue (SLE, SJS, rheumatoid arthritis, vasculitis);

9. Neurological diseases (multiple sclerosis);

10. Allergoses (urticaria, Quincke's edema);

11. Intoxications of various origins (alcohol substitutes, industrial poisons, household chemicals, overdose of drugs);

12. Other (chronic fatigue syndrome).

It should be especially noted that these groups of diseases do not exhaust all the indications for the use of this method. This technique is also justified as an auxiliary accessory method as part of complex therapy in cases where the achievement of success using conventional methods has exhausted itself and the likelihood of a crisis is very high.

The proposed method of discrete plasmapheresis with extracorporeal modification of red blood cells and white blood cells (EMEiL) is as follows:

1. Staff

1.1. The procedure is performed by transfusion doctors and nurses who have undergone special training.

1.2. At all stages of intermittent plasmapheresis, the doctor and nurse ensure constant monitoring of the patient's condition and are responsible for the safety of the procedure.

2. Materials and equipment

2.1. Equipment:

- centrifuge “TsLP 3-3.5”, “TsLP 6-02” with glasses with a capacity of at least 0.75 l;

- a high-frequency generator for sealing polymer tubes or metal rings for sealing polymer tubes;

- scales or stirring scales for measuring the volume of blood collected;

- scales for balancing centrifuge glasses;

- plasma extractor;

- apparatus of extracorporeal ultraviolet ultraviolet blood "Isolde", "Hope", "Hope-O";

- dry-air electric thermostat AT-2, TS-80;

- apparatus for sterile soldering of polymer tubes;

- a rack for hanging polymer containers and bottles;

- polymer containers;

- a device for single-use blood transfusion;

- system - a trunk for transfusion of a solution from a vial into a vial or device for taking blood into a single-use bottle;

- devices for conducting bloodless sampling and the introduction of blood substitutes and red blood cells.

2.2. Materials:

- individual sterile styling (clamps, scissors, napkins, cotton balls, tow, sterile diaper);

- sterile surgical gloves;

- ethanol solution 70%;

- 0.9% sodium chloride solution for infusion, prefabricated (plastic, glass).

3. Procedure

3.1. Preparation of the polymer container.

3.1.1. Check the expiration date and integrity of the polymer container (hemacon (hereinafter referred to as the "container")), prepare it for operation in accordance with the manufacturer's instructions. Visually assess the quality of the preservative (transparency, mechanical inclusion).

3.1.2. Mark container for blood and plasma collection (name of patient, date of collection, department, ward).

3.1.3. Place the container on the scale or stir bar.

3.2. Taking blood.

3.2.1. Preparing for a blood test.

3.2.1.1. Check the tightness, shelf life of the vial or container (hereinafter - the vial) with an isotonic 0.9% sodium chloride solution for infusion, visually assess the transparency of the solution. Check the expiration date of a single-use blood transfusion device.

3.2.1.2. In accordance with the manufacturer’s instructions for the use of a single-use blood transfusion device, connect it to a bottle with an isotonic 0.9% sodium chloride solution for infusion, fill the device with a solution and place the bottle on a transfusion rack.

3.2.1.3. Unfold individual sterile styling.

3.2.2. The process of taking blood.

3.2.2.1. Put the tourniquet on the shoulder, strengthening it with a clamp. Determine the site of venipuncture on the elbow of the patient’s arm, loosen the tourniquet and treat the venipuncture site with an antiseptic solution twice at an interval of 1 minute. After processing the skin, you can not touch it. If it is necessary to palpate the vein after it, the venipuncture site should be re-treated with an antiseptic solution.

3.2.2.2. Tighten the tourniquet, remove the cap from the needle of the container and, without touching the needle, puncture the vein. Loosen the tourniquet slightly, check the blood flow. If blood flows in a continuous stream, fix the needle with a band-aid. If the blood flow is interrupted or absent, check the position of the needle in the vein and change it, if necessary, re-venipuncture with the above procedures and rules. In the case of using a balance without a stirrer to determine the volume of blood taken, it is necessary to periodically (at least every 30-45 seconds) manually mix blood with a preservative in the container. The volume of blood sampling in a large container, without violating the tightness of the small container, is 450-550 ml.

3.2.2.3. After taking blood, put two clamps on the polymer tube at a distance of at least 10 cm from the needle cannula. Treat the tube between the clamps with a 70% solution of ethyl alcohol and cut with sterile scissors.

Remove the harness. Connect a blood transfusion device filled with an isotonic 0.9% sodium chloride solution to the tube with a needle located in the patient’s vein and begin transfusion of the solution to the patient. The first 10 ml of the solution is injected in a jet to prevent thrombosis of the needle, then the rate of introduction of the solution is brought to 30-40 drops per minute.

3.2.2.4. Using a sealer, separate the small container from the large one.

3.3. Centrifuging a blood container.

3.3.1. Place a plastic container with blood in an individual plastic bag and place in a centrifuge cup.

3.3.2. Balance the centrifuge cups with containers in pairs on the scales and install in the centrifuge according to their marking.

3.3.3. It is optimal to perform centrifugation in accordance with the instruction manual for the centrifuge with a separation factor of 5000 g for 7 minutes, which allows achieving a high plasma yield without impurity of cellular elements and without injuring them. To accomplish the task of centrifugation - obtaining plasma with a minimal admixture of blood cells (erythrocytes - not more than 6.0 × 10 ⁹ / l, white blood cells - not more than 0.1 × 10 ⁹ / l, platelets - not more than 50 × 10 ⁹ / l) erythrocyte mass, the product of the separation factor (g) by the centrifugation time in minutes (plateau) should be at least 28,000 and not more than 40,000. Centrifugation time includes acceleration time, but not stop time. The time periods are given only approximately. Each individual centrifuge should evaluate the possibility of using various components for the preparation.

The rotor speed per minute for each centrifuge is determined by the nomogram (Appendix 2 to the "Instructions for the fractionation of canned blood into cellular elements and plasma", M., 1987) or calculated by the formula

$$n=\sqrt{\frac{g\times {10}^8}{1118\times R}},$$

Where

n is the number of revolutions per minute;

g is the separation factor;

R is the radius of the rotor in cm (measured from the center of the rotor to the end of the cup in a horizontal position).

It is possible to adjust the centrifugation time and rotor speed depending on the quality of the resulting plasma.

3.3.4. Centrifugation is carried out at a temperature of + 18- + 22 ° C for 5-10 minutes at 3000 rpm.

3.4. Separation of plasma and leukocyte layer.

3.4.1. After centrifugation is complete, the container with the separated blood should be carefully removed from the centrifuge cup and not allowed to mix the boundary layer and installed in a plasma extractor to transfer the plasma into the plasma container and then dispose of it.

3.4.2. Upon reaching a height of the plasma level above the erythrocyte layer of about 2 cm, the plasma separation is completed.

3.4.3. Connect the small container that was removed before with the container located on the plasma extractor (large container) using the system - a trunk for transferring the solution from the vial to the vial.

Particular attention should be paid to asepsis.

3.4.4. Extrude the leukocyte layer into a small container until the red blood cells appear clearly in the trunk.

3.5. Erythrocyte washing.

3.5.1. In a tube of a large container pretreated with an antiseptic solution or 70% solution of ethyl alcohol, insert a system needle - a line for transfusion of solutions from one bottle to another and add 200-300 ml of a 0.9% sodium chloride solution to the container, carefully mix the red blood cells and the solution. Place a clamp on the tube of the container and centrifuge according to paragraph 3.3.

3.5.2. Remove liquid into an appropriate container up to a distance of 2 cm from the erythrocyte layer. Squeeze the leukocyte layer into a small container. Seal the tube of a large container. Seal the tube of the small container.

 4. Ultraviolet irradiation of leukocyte suspension from the second session

4.1. Uniform and dosed ultraviolet irradiation of a small container (leukocyte suspension with a volume of 100-170 ml) by the Izold apparatus is carried out by passing a leukocyte suspension through a disposable cell for 20-25 minutes. The optimal radiation energy is within 150 J.

5. Drug Administration

5.1. The introduction of drugs in containers with blood products. Using a syringe, introduce antioxidants and cerebroprotectors into a large container (red blood cells):

Mexidol 100 mg; Cytoflavin 200 mg; Phosphogliv 500 mg.

5.2. The introduction of drugs in containers with blood products. Using a syringe, inject interferon inducers, antioxidants and hepatoprotectors into a small container (leukocytes): Cycloferon 250 mg; Heptral 80 mg; Ascorbic acid 200 mg.

Note: In the acute period of the disease, with severe symptoms of inflammation, Prednisolone 30 mg, ATP 1 ml - 1% solution is added.

6. Incubation in the thermostat of small and large containers

6.1. Incubation in a thermostat at t - 37 ° C of a small container (leukocyte suspension with injected drugs) - 120 minutes.

6.2. Incubation in a thermostat at t - 37 ° C of a large container (erythrocyte mass with injected drugs) - 45 minutes.

7. Return of erythrocyte mass and leukocyte suspension (reinfusion)

7.1. At the end of incubation, attach the blood transfusion device to a large container, after diluting it with 0.9% - 200.0 saline. Start red blood cell reinfusion to the patient. Speed is slow (40-60 drops per minute).

7.2. At the end of the incubation, attach the blood transfusion device to a small container. Start reinfusion of the modified WBC suspension to the patient. Speed is slow (40-60 drops per minute).

8. End the session

8.1. Remove the needle from the vein, pre-treating the puncture site with a 70% alcohol solution.

8.2. Apply a tight dressing.

8.3. After plasmapheresis in a patient, measure blood pressure, heart rate and body temperature, evaluate the patient's well-being.

8.4. Give the patient to drink hot sweet tea 200 ml and, if necessary, send to the rest room.

9. Contraindications for discrete plasmapheresis with EMEiL

9.1. Absolute contraindications for discrete plasmapheresis with EMEiL:

- irreversible damage to the brain and other vital organs (acute period of myocardial infarction, pulmonary tuberculosis, acute cerebrovascular accident ...);

- unstoppable bleeding;

- a severe form of anemia.

9.2. Relative contraindications for discrete plasmapheresis with EMEiL:

- bleeding or a high risk of bleeding with gastric ulcer;

- hemodynamic instability (low blood pressure, various rhythm and cardiac conduction disturbances);

- hypoproteinemia (low plasma protein);

- period of menstruation;

- photosensitivity;

- oncological diseases;

- pregnancy, lactation;

- mental illness;

- the impossibility of venous access to the cubital vein;

- in the absence of the possibility of catheterization of the central veins.

To date, the effectiveness of this method has been tested by the practice of application for the period from 1999 to 2011 in the Department of Gravity Surgery of the Voronezh Railway Hospital.

Thus, the proposed method for the treatment of various diseases using discrete plasmapheresis by EMEiL is pathogenetically substantiated and proven effective.

The following is a description of specific clinical examples of the treatment of various diseases using discrete plasmapheresis by EMEiL in the Department of Gravity Surgery of the Voronezh Railway Hospital.

Example 1. Patient B., 35 years old, No. 3111

A brief history: was admitted to the ENT department of the Railway Hospital at st. Voronezh 1 - 05/11/2000, with a diagnosis of Chr. right otitis media, exacerbation. Concomitant diagnosis: Psoriasis, plaque form. Complaints upon admission: intense pain in the right ear with radiation to the teeth and the right temporal region, noise in the right ear, headache, severe general weakness, palpitations. Additionally - itching of the scalp. Objective status: a state of moderate severity. The skin is physiological in color. Over the elbow, knee joints, in the scalp - psoriatic plaques. When examining the right auditory canal hyperemia is noted, palpation - pain when pressing on the tragus. Enlarged posterior cervical lymph nodes on the right are palpated, the skin above them is not changed. In the lungs, vesicular breathing, NPV - 18 per min. Heart sounds are rhythmic, frequent heart rate - 84 per min; HELL - 145/90 mm Hg; t of the body - 37.7 ° C. The tongue is dry, covered with a white coating. The abdomen is soft, painless, the size of the liver according to Kurlov is 10 (+1) * 9 * 8 cm. No edema. Physiological administration is normal.

Clinical diagnosis: Chr. middle right otitis media, exacerbation. Psoriasis, plaque form.

Prescribed treatment: discrete plasmapheresis with EMEiL.

From May 12, 2000 to May 26, 2000, 5 sessions were conducted. Normalization of the general state of health to satisfactory is noted (NPV - 16 rpm; heart rate - 74 rpm; BP - 130/85 mm Hg; body t - 36.6 ° C; manifestations of psoriasis have significantly decreased - plaques are noticeably paler, less prominent over the skin; new elements did not appear). Itchy skin does not bother. The patient was discharged from the hospital on May 30, 2000 with positive dynamics.

From 05.06.2000-19.06.2000, a second cycle (5 sessions) was conducted on an outpatient basis. At the end of the cycle, a positive effect was recorded - the only plaque on the scalp remained on duty, the hearing was completely restored, blood pressure was stable.

Example 2. Patient M., 24 years old, No. 8217

A brief history: was admitted to the trauma unit on January 17, 2001 with a diagnosis of Fracture of the lower third of the left thigh. Was operated on (osteosynthesis). The postoperative period was complicated by osteomyelitis, followed by the formation of fistulas. The subsequent conservative antibacterial and detoxification therapy is not effective - the presence of fistulas, fever, severe intoxication and disability persist.

From April 24, 2001 to May 7, 2001, 1 complete cycle of discrete plasmapheresis with EMEiL was performed (5 sessions). A positive effect was noted: the amount of serous-purulent substance separated from the fistula decreased significantly; body temperature returned to normal (prior to treatment, body temperature rose regularly to 39–40 ° C).

From May 15, 2001 to May 28, 2001, a 2 cycle (5 sessions) was carried out. The patient began to walk, fistulas closed, no pain when walking. The treatment is completed, disability is restored. The patient was discharged from the hospital on 06.06.2001.

Example 3. Patient D., 46 years old, No. 859

A brief history: he was admitted to the therapeutic department on 10.02.2001 with a diagnosis of Chr. gouty polyarthritis, exacerbation. Complaints upon receipt of strong, burning, "gnawing pains" in the area of the knee, elbow, wrist joints, joints of the fingers. Objective status: moderate state. It cannot move independently; it moves with the accompaniment of relatives. The skin of normal color, moist, warm to the touch. The skin in the area of the knee, elbow joints is slightly swollen, hyperemic, hot to the touch, painful on palpation. In the lungs, vesicular breathing, NPV - 16 per min. Heart sounds are rhythmic, rapid, heart rate - 85 per minute; HELL - 140/100 mm Hg; t body - 37.0 ° C. The tongue is wet. The abdomen is soft, painless. The size of the liver according to Kurlov is 11 (+2) * 10 * 9 cm. There is no edema. Physiological administration is normal.

Biochemical blood test - uric acid concentration of 800 μmol / L. Clinical diagnosis: Gout. Chr. gouty polyarthritis, exacerbation. Prescribed treatment: discrete plasmapheresis with EMEiL.

From February 17, 2001 - March 2, 2001, 1 full cycle (5 sessions) was carried out. After the first two sessions, intensification of pain was noted, in the subsequent pain decreased. By the end of the cycle, the patient noted a significant decrease in pain and an increase in the range of motion in the joints.

From March 16, 2001 - March 29, 2001, a 2 cycle (5 sessions) was carried out. A positive effect was also noted - the pain in the joints completely disappeared and also did not bother when moving. According to laboratory studies: the level of blood uric acid normalized to 190 μmol / L.

Example 4. Patient I., 47 years old, No. 5142

A brief history: was admitted to the surgical department on 07/20/2001 with a diagnosis of Erysipelas of the right lower leg. Complaints on admission: pain in the right lower leg at rest and during movement, redness of the skin of the right lower leg, headache, weakness, chills, loss of appetite, nausea and vomiting once.

Objective status: a state of moderate severity. The skin of normal color, moist, warm to the touch. The right tibia is edematous hyperemic, the skin is tense, hot to the touch. In the lungs, vesicular breathing, NPV - 18 per min. Heart sounds are rhythmic, rapid, heart rate - 87 per minute; HELL - 145/90 mm Hg The tongue is wet, coated. The abdomen is soft, painless in all departments. Liver on the edge of the costal arch. Physiological administration is normal.

According to laboratory studies: OAK - leukocytes 11.2 × 10 * 9 / l, ESR - 45 mm / h.

Clinical diagnosis: Erysipelas of the right lower leg.

Prescribed treatment: discrete plasmapheresis with EMEiL.

From August 3, 2001 to September 6, 2001, two cycles were carried out (10 sessions). At the end of treatment, a positive effect was noted: the pain and swelling of the lower leg stopped, the body temperature returned to normal, and the general condition improved. The patient was discharged in satisfactory condition.

Follow-up: treatment outcomes tracked over the past 5 years. There is no relapse of the disease.

Example 5. Patient S., 24 years old, No. 1334

A brief history: was admitted to the surgical department 02.15.2002 with a diagnosis of Furunculosis. Hydradenitis

Complaints at admission: pain in the axillary areas, headache, general weakness, lack of appetite.

Objective status: a state of moderate severity. The skin of normal color, high humidity (hyperhidrosis), warm to the touch. On the outer surface of the right and left shoulder and forearm, in the right and left axillary region, there are multiple boils at various stages of evolution, the skin in the affected areas is hyperemic, moderately swollen, painful on palpation. In the lungs, vesicular breathing, NPV - 17 per min. Heart sounds are rhythmic, frequent heart rate - 88 per min; HELL - 130/80 mm Hg; t body - 38.8 ° C. The tongue is dry, coated. The abdomen is soft, painless in all departments. Liver on the edge of the costal arch. No swelling. Clinical diagnosis: Furunculosis, Hydradenitis. Prescribed treatment: discrete plasmapheresis with EMEiL.

From February 19, 2002– February 26, 2002, 3 sessions were conducted in a hospital setting and from March 1, 2002 – March 4, 2002, 2 sessions were outpatient (a full cycle of 5 sessions). In connection with the improvement of the patient’s health status, on February 27, 2002, the patient was discharged from the hospital. Manifestations of furunculosis and hydradenitis are not observed. Full recovery.

Example 6. Patient P., 53 years old, No. 1-1445

A brief history: was admitted to the gastroenterological department on November 9, 2005 with a diagnosis of Acute toxic hepatitis (poisoning with alcohol substitutes). Upon receipt, a moderate condition. Complaints at admission: general weakness, nausea, bitterness in the mouth, lack of appetite, unstable stools, skin itching, feeling of heaviness and dull pain in the right hypochondrium.

Objective status: upon examination, skin, icteric sclera, moderate enlargement of the liver, pain on palpation, “+” symptom of Murphy, Ortner, Kera. Biochemical blood test - bilirubin 300 μmol / L, ALT - 800 U / L, ACT - 700 U / L.

Clinical diagnosis: Acute toxic hepatitis of moderate severity, cholangitis.

Prescribed treatment: discrete plasmapheresis with EMEiL.

Three complete cycles were carried out (5 sessions each). The interval between sessions is 2 days. By the end of the 1st cycle, there was a slight improvement in well-being: appetite appeared, weakness decreased. According to laboratory studies: bilirubin 155 μmol / L, ALT - 640 U / L, ACT - 450 U / L. After 16 days, a 2 cycle was carried out and 20 days after a 2 cycle 3 cycle was carried out. At the end of treatment, appetite was restored, jaundice, dyspepsia, general weakness disappeared, disability was restored, biochemical parameters returned: bilirubin 18 µmol / L, ALT - 35 U / L, ACT - 32 U / L. Treatment led to recovery.

Example 7. Patient S., 31 years old, No. 2716

A brief history: entered on March 18, 2007 in the therapeutic department with a diagnosis of Chr. hepatitis C, active.

Complaints at admission: general weakness, fatigue, irritability, heaviness in the right hypochondrium, subfebrile condition, drowsiness during the day, bleeding gums.

Objective status: a state of moderate severity. The skin, sclera are icteric, clean. In the lungs, vesicular breathing, BH - 18 per min. Heart sounds are rhythmic, frequent heart rate - 84 per min; HELL - 120/70 mm Hg; t body - 37.6 ° C.

The tongue is dry, covered with a white coating. The abdomen is soft, slightly painful in the right hypochondrium, the edge of the liver is +2 cm, pointed, painful on palpation, the spleen is not palpable. Biochemical analysis: bilirubin 125 μmol / L, ALT - 750 U / L, ACT - 680 U / L. HCV-PHK - "+" result.

Clinical diagnosis: Chr. viral hepatitis C (aHCV +, RNA +), moderate activity, replicative phase.

Prescribed treatment: discrete plasmapheresis with EMEiL.

From March 19, 2007 - April 2, 2007, a full cycle was carried out (5 sessions). By the end of the 1st cycle, there was a significant improvement in well-being: appetite appeared, weakness decreased, and body temperature returned to normal.

From April 17, 2007 to April 4, 2007, a 2 cycle (5 sessions) was carried out.

From May 25, 2007 to June 7, 2007, a 3 cycle (5 sessions) was carried out.

At the end of treatment, clinical and laboratory remission was noted: there were no active complaints, normalization of laboratory parameters. The patient was discharged from the hospital in satisfactory condition.

Example 8. Patient Ch., 46 years old, No. 11765

A brief history: he was admitted to the gastroenterological department with a diagnosis of:

Acute toxic hepatitis.

Complaints at admission: general weakness, fatigue, heaviness in the right hypochondrium, headache that occurs in the evening, disturbance of accommodation, dry mouth, nausea, darkening of urine and lightening of feces, yellowing of the skin and sclera.

Objective status: a state of moderate severity. On examination, the skin is icteric in color, the sclera is icteric. In the lungs, vesicular breathing, BH - 18 per min. Heart sounds are rhythmic, frequent heart rate - 92 per minute. The abdomen is soft, painful in the right hypochondrium. The lower edge of the right lobe of the liver protrudes 3 cm from the edge of the right costal arch. According to laboratory tests: a biochemical blood test - bilirubin level of 350 μmol / L, AlAt - 1150 U / L, AcAt - 950 U / L.

Clinical diagnosis: Acute toxic hepatitis (poisoning with alcohol substitutes), a high degree of activity.

Prescribed treatment: discrete plasmapheresis with EMEiL.

From November 3, 2006 to November 23-23, 2006, a complete cycle was carried out (5 sessions) with an interval between procedures of 2-3 days. By the end of the first cycle, there was a significant improvement in well-being: appetite appeared, weakness decreased.

According to laboratory studies: a biochemical blood test - bilirubin level of 155 μmol / L, AlAt - 300 U / L, AsAt - 180 U / L.

From November 30, 2006 to December 14, 2006, the second cycle was carried out (5 sessions). At the end of treatment, favorable dynamics were observed - the condition was satisfactory. The skin and sclera of physiological color, clean. Liver on the edge of the costal arch. Physiological administration is normal. According to laboratory studies: a biochemical blood test - a bilirubin level of 20 μmol / L, AlAt - 40 U / L, AsAt - 34 U / L. The patient's health has fully recovered.

Example 9. Patient K., 44 years old, No. 7484

A brief history: was admitted to the gastroenterological department with a diagnosis of Peptic ulcer, exacerbation. Intestinal dysbiosis. On October 18, 2005, after unsuccessful treatment (antibacterial therapy, hydrochloric acid secretion inhibitors), she was referred for consultation in the OGH.

Complaints at admission: for aching, severe, "hungry" pains in the epigastric region. Vomiting food up to 3 times, heartburn. At night the pain intensifies.

Objective status: condition closer to satisfactory. Skin, sclera clean. In the lungs, vesicular breathing, NPV - 17 per min. Heart sounds are quickened, heart rate - 82 per min; HELL - 135/70 mm Hg; t body - 36.6 ° C. Tongue, moist, densely covered with a dirty white coating. The abdomen is soft, painful in epigastrium, the liver is +1 cm. According to FGS, an ulcer of the antrum is found to be 1.5-1.0 cm with fibrin at the bottom.

Clinical diagnosis: gastric ulcer, exacerbation. Intestinal dysbiosis.

Prescribed treatment: discrete plasmapheresis with EMEiL.

From October 18, 2005 to October 31, 2005, a full cycle was carried out (5 sessions). There are no complaints at the end of treatment. According to the FGS on 02.11.2005, the total epithelization of the ulcer. At the time of discharge, complete recovery.

Example 10. Patient S., 50 years old, No. 3397

A brief history: was admitted on May 10, 2005 to the urology department with a diagnosis of Neoplasm of the bladder, hr. pyelonephritis.

May 15, 2005 was operated on for a neoplasm of the bladder. In the postoperative period, the formation of a postoperative fistula occurred, which did not heal for a long time, despite the treatment (antibacterial, detoxification and restorative therapy, local treatment).

Prescribed treatment: discrete plasmapheresis with EMEiL.

From June 9, 2005 to June 23, 2005, a complete cycle was carried out (5 sessions). As a result, the fistula was closed, further healing of the postoperative wound occurred without features. The patient was discharged in satisfactory condition.

Further, in order to prevent metastasis on an outpatient basis, 2 cycles were carried out:

From July 6, 2005 - July 20, 2005, the second cycle (5 sessions).

From 08/22/2005 - 09/09/2005, the third cycle (5 sessions).

At the end of the course of treatment, the general condition of the patient is satisfactory, there are no complaints.

Follow-up: treatment outcomes tracked in recent years. Relapse of the disease in 2011 was not observed. The treatment led to a complete recovery.

For the first time, the method of discrete plasmapheresis with EMEiL for endotoxicosis of various etiologies has been scientifically substantiated, developed and applied. The value of discrete plasmapheresis with EMEiL as a method of emergency detoxification and immunocorrection in patients with various nosologies complicated by endotoxemia has been proved. A technique has been developed for discrete plasmapheresis with EMEiL, which will reduce the length of stay of patients in the intensive care unit, reduce the cost of expensive treatment and depreciation of medical equipment, diagnostic tests. All this will make it possible to increase the effectiveness of detoxification therapy and reduce the risk of side effects and complications in the recovery period, reduce the length of the patient’s stay in hospital and increase the time of stable remission, reduce the amount of drugs consumed (expensive drugs and have a number of side effects for the body), extend the period quality of life and reduced mortality.

The high potential need for discrete therapeutic plasmapheresis with EMEiL is due to its significant socio-economic efficiency.

The method is easily reproducible both in outpatient and inpatient settings. Thus, the claimed invention meets the criterion of "industrial applicability".

List of references

1. Shmelev E.I., Stepanyan I.E. Hemapheresis methods in pulmonological practice. Materials of the first conference of the Moscow Society of Hemapheresis. M., 1993. S.163-170.

2. Stepanyan I.E., Ozerova L.V., Shmelev E.I. The results of complex treatment of patients with alveolitis using hemapheresis. Pulmonology. 1993. No. 3. S.15-19.

3. Gevorkyan MG, Tazulakhova E.B., Ershov F.I. Antiviral substances. Minsk "Belarus", 1984. S.127-137.

4. Ershov F.I., Chizhov N.P., Tazulakhova E.B. Antiviral agents. St. Petersburg, 1993.104 s.

5. Ershov F. I. The interferon system is normal and in pathology. M .: Medicine, 1996.240 s.

6. Ershov F.I., Kovalenko A.L., Romantsov M.G., Golubev S.Yu. Cycloferon. Clinical Pharmacology and Therapy: A Guide for Physicians. St. Petersburg, 1998.109 s.

7. Bazhan S.I., Belova O.E. Molecular genetic aspects of the induction and antiviral effect of interferon. Vestnik RAMS, No. 3, 1998. S.18-24.

8. Goryacheva L.G., Romantsov M.G., Botvineva V.V. Cycloferon. Effective remedy for pediatrics. SPb., 2002.

9. David M. Transcription factors in interferon signaling. Pharmacol Ther. 1995.65: 149-161.

10. Asadullah K., Sterry W., Stephanek K. et al. IL-10 is a key cytokine in psoriasis. Proof of principle by IL-10 therapy: a new therapeutic approach. J Clin Invest 1998.101: 4: 783-794.

11. Ortega L.G., McCotter M.D., Henry G. L., McCormack SJ. mechanism of interferon action. Biochemical and genetic evidence for the intermolecular association ofRNA-depended protein kinase PKR from human with ells. Virology. 1996.215 (1): 31-39.

12. The immune system and antiviral immunity. Chapter 3. Freidlin I.S. Textbook "Questions of General Virology." Ed. Kiseleva O.I., St. Petersburg., GMA named after Mechnikov I.I., 2007.

13. Freidlin I.S. The immune system and its defects. A manual for doctors, St. Petersburg, NTFF Polisan, 1998, 103 pp.

14. Baron S, Tyring SK, Fleischmann WR Jr., et al. The interferons. Mechanisms of action and clinical applications. JAMA 1991.266 (10): 1375-1383.

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Claims (1)

A method of conducting therapeutic discrete plasmapheresis, which consists in centrifuging the blood received from the patient into plasma and erythro-leukomass diluted with an isotonic sodium chloride solution, followed by its return to the venous bed, characterized in that interferon inducers, hepatoprotectors and antioxidants are introduced into the leukocyte suspension below therapeutic, after which the incubation of the leukocyte suspension at t - 37 ° C is carried out for 120 minutes, then they return to the patient’s venous bed, to the erythrocyte m Asses are administered cerebroprotectors, hepatoprotectors and antioxidants at doses lower than therapeutic, after which they erythrocyte mass is incubated at t - 37 ° C for 45 minutes, then they are returned to the patient’s venous bed from the second session of each cycle in the absence of contraindications before incubation of leukocyte suspension with the drugs introduced produce ultraviolet radiation (UFO-150 J), the duration of treatment is an average of three cycles of 5 sessions with a recommended interval of 2 days, duration The duration of the session is at least 3.5 hours and not more than 4.5 hours, the interval between the 1st and 2nd cycle is 2 weeks, between 2 and 3-4 weeks, the general course of treatment is 2-3 months.