RU2134593C1 - Method of indirect endolymphic antibiotic therapy of patients ill with sepsis - Google Patents

Abstract

FIELD: medicine, particularly, surgery. SUBSTANCE: method includes indirect endolymphic antibiotic therapy. In this case, antibiotic is infused into subcutaneous fat. Infiltrate is created. Then pneumocompression is carried out in infiltrate region. In particular case, infusion is performed into subcutaneous fat of anteroexternal surface of femurs. In particular case, antibiotic is used in the form of gentamycin in 0.9-% solution of sodium chloride. EFFECT: reduced therapeutic dose of antibiotic. 3 cl, 1 tbl

Description

 The invention relates to medicine, namely to surgery, and can be used in patients with acute and chronic inflammatory processes accompanied by endotoxemia.

 There are various methods of antibiotic therapy for patients with sepsis that occurs with purulent-inflammatory diseases [1]. The disadvantages of traditional antibiotic therapy (subcutaneous, intramuscular, intravenous, intraarterial administration) is the need to use large doses of the antibiotic to overcome the hemolymphatic barrier, which is fraught with the development of mycosis, immunosuppression, allergic reactions. Direct endolymphatic administration of drugs through a catheterized peripheral vessel eliminated these shortcomings [1, 2]. However, a significant drawback of this method is the need for surgical intervention using microsurgical techniques.

 There is also known a method of indirect drug saturation of the lymphatic system, in which subcutaneously injected drugs depolarizing the main substance of the connective tissue (lidase, thrombolysin, chymopsin, etc.) are injected and create one and a half to two hours phlebogipertension in the injection area [3].

 This method is adopted as a prototype.

 However, the possible reactions of the body to additional drugs and the duration of the procedure itself limit the widespread use of the known method.

 Known methods of introducing antibiotics into the lymphatic system are designed to create an antibiotic concentration in the blood and lymph that is sufficient for a therapeutic, microflora-suppressing action, provided that the total amount is reduced. Clinical studies on the direct and indirect endolymphatic administration of antibiotics have revealed the fact of a long-lasting minimally damaging concentration of antibiotics in the blood and lymph (up to 24 hours) after a single dose. The peak concentration, determined 60–80 min after endolymphatic administration of a single dose, is significantly higher than the maximum concentration after intravenous or intra-arterial administration [1, 3]. Such a mechanism of pharmacokinetics is characteristic of all antibiotics of the cephalosporin and aminoglycoside series. It follows that the most effective of all known methods of introducing antibiotics into the body is the introduction into the lymphatic system.

 Infusion of an antibiotic in physiological saline into the subcutaneous tissue of the thigh creates the so-called "hydration", or "water infiltrate", which allows, firstly, by virtue of the dilution of the antibiotic to reduce its toxic effect on the interstitial space; secondly, due to the mechanical increase in hydrostatic pressure in the interstitium, to open the interendothelial cracks (the effect of hydraulic expansion of the filament elements of the endothelial cells of the lymphatic capillary). The simultaneous mechanical compression of the capillary links of the arteriovenous system contributes to the predominant penetration of drugs into the lymphatic channel. The use of relatively large volumes of solution compared to traditional subcutaneous or intramuscular administration increases the contact area of the antibiotic and microvascular lymphatic channel, which resorb from the extracellular spaces. Subsequent massage of "water infiltrate" allows you to implement the above conditions directly into the effect of saturating the lymphatic system with an antibiotic. The mechanical effect during massage among many of its derivatives has an important property for our case of increasing pressure in the interstitial drug solution. There is the so-called “reverse” Starling effect, in which the fluid and the particles enclosed in it are “filtered” from the intercellular space into the vascular, mainly lymphatic system. The use of a special device (AKPU-5), consisting of a pneumatic compressor and an eight-section cuff, allows you to set and control the required pressure and its mode, as well as replace manual labor with automated.

 Thus, the proposed method for the indirect administration of drugs into the lymphatic system has several advantages over other injection methods, namely, it reduces the time of the procedure itself, reduces the therapeutic dose of the antibiotic, and eliminates the introduction of additional drugs with their possible adverse effects on the macroorganism.

 In the well-known scientific-medical and patent documentation, no solutions were found for similar signs. Thus, the proposed solution meets the criterion: "Significant differences."

 The method is as follows.

 A drug composition is created consisting of an antibiotic (gentamicin at a rate of 0.7 μg / kg) and an isotonic solution of 0.9% sodium chloride solution (physiological solution at a rate of 6-8 ml / kg). The resulting volume corresponds to 400-500 ml.

 A glass container with a solution is mounted on a tripod at a height of 1-1.5 m above the injection level. A standard system for transfusion of solutions and blood substitutes is attached to the tank. The patient fits horizontally. After the needle is inserted from the transfusion system of solutions and blood substitutes (the length of the needle is 6-8 cm, the lumen diameter is 1 mm) into the subcutaneous tissue of the front-outer surface of the thigh, make sure that the skin is pierced and no blood is released from the needle. The needle is fixed to the skin with a band-aid and connected to a filled system for transfusion of fluids. A similar procedure is simultaneously performed on the other lower limb. Infusion is performed at a rate of 80-100 drops per minute. This step takes about 60 minutes. After creating “hydration infiltrates” in the subcutaneous tissue of the thighs, eight-section cuffs from an AKPU-5 type pneumatic device are put on limbs. Pneumocompression is carried out in the "rising wave" mode, in which the pressure in the cuffs is created sequentially, starting with the distal and ending with the proximal section. The set parameters are as follows: cuff pressure 100-120 mm Hg. Art., the duration of the cycle 120 s, the duration of the session 30-40 minutes Contraindications for the proposed method of administration of drugs are: thrombophlebitis of the lower extremities, lymphedema of the II-III stage, decompensated heart failure, individual intolerance to antibiotics.

 The method passed an experimental test at the Department of Surgery of the Ivanovo State Medical Institute on 18 outbred dogs weighing 8-12 kg. Nine animals were injected with gentamicin at a dose of 1.4 mg / kg in the front upper thigh [6] and the remaining nine animals (main group) were treated with the same drug, in the same dose, by the proposed method. The essence of the latter was as follows: an antibiotic was injected into the subcutaneous fat of the thigh in 20 ml of physiological saline and immediately began an alternating manual adsorption and transport lymphatic massage for 30 minutes. In animals of both groups, blood and lymph were taken to determine the concentration of gentamicin after 0.5; 1; 1.5; 2; 3; 6; 12; 24 hours after the massage. Blood was taken from the femoral vein, lymph from the drained thoracic duct. After 6; 12; For 24 hours, three animals of both groups were removed from the experiment by an overdose of thiopental sodium, administered intrapleurally. The concentration of gentamicin in blood serum, lymph, inguinal, paraaortic and cervical lymph nodes, liver, stomach wall and pancreas was determined by agar diffusion using you as a test microbe. Subtilis TCC 8241 [4, 5].

 In both cases of antibiotic administration, the maximum concentration of the drug is reached within the first hour after the injection. In the subsequent periods of observation, there is a slow decrease in the concentration of serum antibiotics, reaching a minimum (from 0.2 to 1.0 μg / ml.) By 24 hours of exposure. It should be noted that in this case, the maximum concentration of gentamicin in the blood in no case did not exceed the threshold level (10-12 μg / ml), above which the risk of nephro- and ototoxic effects of the drug increases [6].

 In lymph serum, some differences in drug concentration with different methods of administration were recorded only in the first 30 minutes. In the control group, the antibiotic level reached 8.4 ± 0.23 μg / ml, and in the experimental group - 6.6 ± 0.19 μg / ml. This phenomenon is explained by the difference in the time intervals of lymph sampling for the study at the end of the injection. In classical lymphotropic administration, the start of the countdown is the cuff removal time, which is carried out 1.5-2 hours after the end of the injection itself. In the proposed embodiment, the countdown is after the completion of lymphatic massage (30 minutes after the end of the injection). In all other periods of observation, there were no significant differences in the size measured in both experimental groups.

 Lymphotropic administration of an antibiotic in the studied modifications contributes to the creation of a minimum damaging concentration of the drug (MPC) for virtually all pathogens of surgical infection in both regional and remote lymph nodes and organs during 6-12 hours of observation.

 By 24 hours, IPC is retained only for some pathogens. Information on the IPC of gentamicin is obtained from [6]. Both modifications of the indirect administration of the antibiotic into the lymphatic channel give complete coincidence of concentrations in the studied organs.

Clinical trials of the method took place at the Department of Surgical Diseases No. 1 of the Moscow Medical Dental Institute, on the basis of Clinical Hospital No. 56 in 96 patients. All observations were combined in two groups: 1) control (45 patients) - gentamicin was injected according to the method [3] of drug saturation of the lymphatic system into the region of the posterior surface of the leg; 2) the main (51 patient) - gentamicin at a dose of 1.4 μg / kg was injected into the subcutaneous tissue of the anterior surface of the thigh with physiological saline in a volume of 6-8 ml / kg. The procedure consisted of two stages. The first was the infusion of physiological saline heated to 40 ^° C with a selected drug using a standard disposable blood transfusion system. After the needle was inserted into the subcutaneous tissue, infusion began. The vessel containing the transfused liquid was installed at a height of 1-1.5 m from the level of the patient in a horizontal position. After the subcutaneous injection of fluid, the second stage begins. An eight-section cuff of an AKPU-5 type installation was worn over the entire lower limb. Pneumocompression was carried out in the "rising wave" mode, in which the pressure in the cuffs is created sequentially, starting with the distal and ending with the proximal sections. Cuff pressure 100-120 mmHg. Art., the duration of the cycle 10-30 s, the duration of the session 30-40 minutes The age of patients ranged from 30 to 70 years. In addition to the clinical examination, the content of gentamicin in the blood serum was studied in all patients at 6, 12, 24 hours after the first injection (see table).

 The data given in the table indicate that the lymphotropic administration of gentamicin in the classical and proposed variants under the conditions of the clinic creates a sufficient MIC of the antibiotic in the blood serum within 12 hours after the injection and does not have significant differences in this indicator. The clinical effectiveness of treatment in the control and main groups also did not differ.

 Example 1. Patient D., 30 years old, was admitted with complaints of malaise, in the evenings - low-grade fever. Six months ago, he underwent appendectomy for destructive appendicitis. The postoperative period was difficult. These symptoms appeared 3-4 months ago. In various studies, a purulent focus was not detected. In an immunological study, an increase in immunocirculating complexes of 3 fractions. Staphylococcus is sown from blood. The treatment was carried out according to the proposed methodology (10 sessions). Her health improved, her appetite appeared, her body temperature returned to normal. Threefold blood culture inoculation did not reveal the pathogen. CEC indicators returned to normal after 1 month. The patient was discharged in satisfactory condition.

 Example 2. Patient K., 41 years old. She suffered from periodontitis. For 2 months before admission to the clinic I felt weak, in the evenings - chills. Clinical temperature control in the clinic confirmed the presence of low-grade fever. No other inflammatory pathology was detected. CEC indicators are increased. Conducted 10 treatment sessions by the proposed method. Body temperature returned to normal, CEC values returned to normal after 3 weeks. Inflammation in the oral cavity disappeared, which allowed the dentist to operate on the patient.

 Example 3. Patient K., 43 years old, was admitted to the clinic with appendicular infiltrate. After 6 sessions according to the proposed method, body temperature returned to normal. The leukocyte formula is within normal limits. Infiltrate was almost completely resolved. The patient was discharged from the hospital on the 8th day.

 Thus, the proposed method has advantages over the known one: it allows to reduce the time of the procedure by more than 3 times, as well as to exclude the introduction of additional drugs that can cause unwanted side effects.

 The method is proposed for implementation in the clinic as a method of choice for various inflammatory and septic conditions.

Sources of information
1. Panchenkov R. T., Vyrenkov Yu.E., Yarema I.V., Scherbakova E.G. Endolymphatic antibiotic therapy. M., Medicine, 1984, 240 p.

 2. Dzhumabaev S.U., Buyanov V.M., Danilov K.Yu. et al. Lymphotropic antibiotic therapy. Wedge. surgery. 1987, N 1, S. 14-17.

 3. Buyanov V. M., Danilov K. Yu., Radzikhovsky A. P. Drug saturation of the lymphatic system. Kiev. "Science Dumka", 1991, 136 pp.

4. Gauze T.F. Eremomycin is a new antibiotic from the group of cyclic peptides. Antibiotics and chemotherapy. 1989, N 5, S. 384
5. Filipposyants S. G., Malkova I. V. The study of the pharmacokinetics of eremomycin in the experiment. Antibiotics and Medbiotechnology, N 7, S. 511-516.

 6. Havashin S.M., Fomina I.P. Rational antibiotic therapy. M., Medicine, 1982, 496 p.

Claims (3)

 1. The method of indirect endolymphatic antibiotic therapy for patients with sepsis, including infusion of the antibiotic into the subcutaneous tissue, characterized in that during the infusion of the antibiotic they create an infiltrate followed by pneumocompression of the infiltrate area.  2. The method according to claim 1, characterized in that the infusion is carried out in the subcutaneous tissue of the front-outer surface of the thighs.  3. The method according to claim 1, characterized in that gentamicin in a 0.9% sodium chloride solution is used as an antibiotic.

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