A method of treating patients with multiple organ failure

 

(57) Abstract:

The invention relates to medicine, namely to intensive care, and for the treatment of patients with multi-organ failure. To do this, in the complex of intensive therapy offer to include the combined introduction of lacenterra: intramuscular injections of 10 thousand IU enter daily, combining with 3x endobronchial introduction 10 thousand IU every other day. Using the proposed method allows to reduce twice the mortality and an average of 1.7 times to reduce the duration of stay of patients in intensive care units and intensive care. 5 table.

The invention relates to medicine, namely to immunology, and can be used for immunotherapy of patients in critical conditions.

Despite some successes in the treatment of patients in critical conditions, this group of patients remains the most difficult for therapy and prognosis. The syndrome of multiple organ failure (SPSS) is a serious complication in patients of intensive care units, occurs in 25-30% of cases [7, 14] and is characterized by high mortality [1]. The basis of the pathogenesis of SPONTANEOUS amounts of nonspecific dissimilar the main compounds (cytokines, eicosanoids, components of the complement system, oxygen radicals, nitric oxide and others). This leads to damage to cells and tissue, organ and system failure - respiratory, hepatic, renal, including failure of the immune system. In patients with SPONTANEOUS revealed a direct relationship with the degree of violation of various components of the immune system from the severity of the disease, severity of Exo - and endotoxemia, disorders of homeostasis [3, 8]. In these circumstances, it cannot perform its main function - implementation of immunological surveillance that leads to the development of septic complications and exacerbates SPON [8, 10, 17]. According to most researchers [11, 14] it is the lungs are the first and main target organ, smitten with SPSS. Often registers a combination of respiratory failure with acute renal and metabolic disorders [14] .

There is a method of treatment of patients with multi-organ failure, including the prescription of antibiotics, a means of detoxification, correction of acid-base status, the introduction of protein and symptomatic drugs [3, 10] . However, the complex events of intensive therapy does not always produce positive results, mortality is ostatochnomu develops a state of profound immunosuppression, denoted by the term "immunoparalysis" with impaired functional activity of monocytes, which requires the inclusion of immunotropic funds. The most reasonable we can assume the use of cytokines [4, 11]. Patients with peritonitis [13] and sepsis [9] in the combined therapy was included lacapere representing the integrated product of the first cytokines (nonspecific) phase of the immune response (IFN, IL-1, 6, 12, TNF) in their natural ratio. Lacapere was injected intramuscularly and/or intraperitoneally (if programmed the bailouts) to 10 thousand ME every other day for 3-5 days. However, this treatment regimen is not effective enough as a short course (3-5 injections) and the lack of dose rate to 60-80 thousand ME have no direct effect on immunocompetent cells are the main target organ syndrome multiple organ failure - lung.

The severity of disorders of the immune system and lung damage in patients in critical conditions demand new schemes to prescribe the drug.

The goal is to increase the efficiency of treatment of patients with multi-organ failure by affecting immunocompetent cells of the target organ is the lung.

Given that patients in CSEM data in 78% of cases occur acute lung injury (nosocomial pneumonia, respiratory distress syndrome of adults). In this regard, we believe it is necessary in addition to systemic intramuscular injection of lacenterra conduct endobronchial administration of the drug to act physiologically balanced complex of natural cytokines as at the system level, and directly on the immune and epithelial cells of the broncho-pulmonary system.

As a result, it was obtained that the optimal scheme is combined drug: combination of intramuscular injection of lacenterra with his endobronchial introduction. This is because when multiple organ failure is logged lesions multiple organs and systems, it is therefore necessary systemic (intramuscular) injection. But because the leading is usually the lungs, the local impact of the complex cytokine exerts a stimulating effect and helps to break the vicious cycle: infection (severe injury) - IDS - infection. This effect is associated with the mechanisms of action of lacenterra. It consists of a complex of the first cytokines (nonspecific) phase of the immune response, which is produced by leukocytes saichek a balanced ratio appropriate adequate cytokine response of leukocytes (primarily monocytes) healthy people. Cytokines that are part of lacenterra serve as mediators of intercellular interactions at the elimination of antigens at the level of the macrophage-T-helper lymphocyte-neutrophil fagozyt, without the participation of antibodies. When introduced into the body of the patient they have both a substitution and Primerose action, increase the expression of antigens HLAI and HLAII on lymphocytes and macrophages, which provides improved process of antigen presentation, signal transmission, initiating the immune response, and thus serves as a stimulus for the development of adequate specific immune response. In subsequent action lacenterra realized through the activation of cell proliferation, differentiation and functional activity of immunoregulatory lymphocyte subpopulations. Under lacenterra is undergoing profound changes in the immune system: increases the number of immune effectors, an increasing number of differentiated subpopulations, stimulated their functional activity. First of all these processes occur in the system T-lymphocytes mainly due to the activation of Th1 population and phagocytic systems, the immunological paralysis".

We offer the following scheme: intramuscular injection of lacenterra 10 thousand ME to conduct daily 10 and simultaneously to enter lacapere in the bronchi 10 thousand ME, divorced, for example, in 10 ml of water for injection to improve the distribution of the drug through day 3.

According to this method, treated 47 patients with multiorgan failure. Table 1 presents comparative data of clinical and biochemical parameters in patients receiving different treatment. The majority (74,5%) were on mechanical ventilation from 2 to 20 days.

group 3 patients received only antibiotics, a means of detoxification, correction of acid-base balance, protein drugs, symptomatic treatment.

group 2 - patients who additionally received combined introduction of lacenterra: daily intramuscularly for 10 thousand ME 10 and endobronchial introduction every other day for 10 thousand ME 3.

group 1 - patients treated in the complex treatment of lacapere a day intramuscularly 7-10.

As can be seen from the table, clinical and biochemical parameters in patients of all three groups did not differ from each other, but significantly differed (p<0,05-0,01) with indicators of healthy donors. Anal who receive emitting the combined introduction of lacenterra, normalization of clinical and laboratory parameters occurred significantly earlier than in patients receiving therapy without immunomodulators. In addition, a number of signs - heart rate, respiratory rate, leukocyte index of intoxication, creatinine, lactic acid, restore, they did it faster (p<0.05) than in patients receiving intramuscular injection of lacenterra.

In tables 3 and 4 presents the dynamics of indicators of immunity in patients with SPONTANEOUS treated with different treatment regimens, and the significance of differences between them.

Thus, as can be seen from table 3, in patients of all studied groups at the beginning of the disease were recorded immunodeficiency combined type, characterized by low absolute number of T-lymphocytes, failure of phagocytosis, hypogammaglobulinemia IgA, hypercytokinemia, the increase in CEC. In groups of patients SPSS treated with immunotropic therapy, there was a positive dynamics of immunological indicators: increased content of T-lymphocytes, phagocytic activity, increased levels of IgG, decreased the number of circulating immune complexes, increased soderzhaniya aggravation of T-cell deficiency, phagocytic activity of neutrophils, decreased content of IgA and registered a tendency to decrease in IgM and IgG, was almost unchanged level of immune interferon (IFN) responsible for activation of cellular immunity. Increased content of the CEC.

However, examining the significance of differences of changes in indicators of immunity in patients analyzed groups (table 4), we have found that it is in group 2 of patients treated with combined method of introducing lacenterra, the above changes were more reliable. It should be noted that a significant increase in IFN (p<0.01), and IgA (p<0.01), and IgG (p<0.05), and phagocytic activity of neutrophils (p<0.05) and the decrease in CEC (p<0,01) was registered even in comparison with a group of patients, who underwent intramuscular injection of lacenterra.

Examining the duration of patients ' stay in the intensive care unit and intensive care and mortality (table 5), we established that the use of the proposed method allows to reduce in 2 times the mortality and an average of 1.7 times to reduce the duration of stay of patients in the ICU.

Example.

Patient P., aged 35, arrived in KKB 17.04.2000, Department of pulmonology, 20.04.2000, fair exudative pleurisy on the right, NAM Art. III , DIC I century, SPON. Upon admission to the ICU the patient complains of shortness of breath, pain when breathing, slowed down, respiratory rate 22 in 1 minute, heart rate 93 in 1 minute, HELL 140/87 mm RT.article Blood counts at admission to the intensive care unit and intensive care - HB-93 g/l Ht-28%, Er-3,01012/l, Le-3,1109/l, erythrocyte sedimentation rate of 29 mm/h, e-0, p-9, p-52, l-35, m-4, toxic granularity of neutrophils, CRP-2.4 mmol/l and 2.4, urea 12.8 mmol/l, creatinine 230 µmol/l, total bilirubin 30.0 µmol/l, lactic acid, 2.0 mmol/l, glucose of 6.4 mmol/l, total protein to 58.1 g/l, E-ROCK-38%, 0,412109/l EAC-ROCK-15%, rate £ 0.162 g/l, CEC-160 unit opt.PL, IgM-0,69 g/l, IgG-7,1 g/l, IgA-0,48 g/l, IL-6-142 PG/ml, IFN-16 PG/ml, F-42%, FC to 2.0. Received complex drugs intensive care and lacapere intramuscularly for 10 thousand ME daily 10 and endobronhialno 10 thousand ME (in 10 ml of water for injection) through day 3. After 3 days improved condition: normalized breathing rate, disappeared cough, body temperature decreased from 39.6 37.8. On the 5th day pain disappeared, the body temperature 37,1oC, respiratory rate 17 in 1 minute, heart rate of 70 beats per minute. In the analysis of blood - HB-94 g/l, Ht-30%, Er-4,31012/l, Le-6,0109/l, erythrocyte sedimentation rate of 32 mm/h, e-2, p-9, p-56, l-26, m-7, SLO-0.6 mmol/l, total protein 52,0 g/l, E-ROCK-50%, 0,78109/l EAC-ROCK-20%, 0.312 g/l, CEC-100% opt. square , IgM-0.7 g/l, IgG and 8.1 g/l, IgA-0.6 g/l, IL-6-48 PG/ml, IFN-36 PG/ml, F-52%, FC to 2.4.

On the 9th day in a satisfactory condition, the patient was transferred to our clinic, from which 8 days was discharged. The total number of days of hospital stay - 20. By day 15: satisfactory, nose breathing is free, clear consciousness, respiratory rate 17 in 1 minute, heart rate of 71 in 1 minute, the blood - HB-98 g/l, Ht-32%, Er-4,41012/l, Le-6,2109/l, erythrocyte sedimentation rate of 12 mm/h, e-2, p-1, p-58, l-31, m-8, CRP-0, urea 4.3 mmol/l, creatinine 70,0 µmol/l, total bilirubin 8.5 µmol/l, lactic acid, 1,6 mmol/l, glucose of 5.1 mmol/l, total protein of 69.9 g/l, E-ROCK-64%, 1,27109/l EAC-ROCK-20%, 0,42 g/l, CEC-60% of the protected area. square , IgM-0.9 g/l, IgG-9.4 g/l, IgA-1.0 g/l, IL-6-12 PG/ml, IFN-60 PG/ml, F-68%, FC-3,1.

Thus, the dynamics of clinical and immunological parameters clearly indicates the inclusion of lacenterra by the proposed method in treatment of patients with multi-organ failure.

Thus, inclusion in the complex treatment of patients with the syndrome of multiple organ failure lacenterra by combined dose rate of 130 thousand ME) provides significant clinical effect and to improve the prognosis.

Clinical experience shows that lacapere is a reliable and safe means of immunocorrection in SPSS, which considerably improves the efficiency of treatment of such patients.

Literature

1. Gumerov, A. A., Mironov, P. I., Viktorov centuries, Viktorova T. C. Metabolic and immunological changes in appendicular peritonitis, complicated by multiorgan failure. //The Bulletin of the surgery. - 1997. , 156, 5. - S. 61-64.

2. Zolotokrylin E. C. Issues of pathogenesis and treatment of multiple organ failure in patients with severe trauma and massive blood loss in the early postresuscitation period. //Anesthesiology and resuscitation. - 1996. - 1. - S. 9-13.

3. Kälin N. Y. Immunobiochemical mechanisms intoxication syndrome in acute diffuse peritonitis. //Anesthesiology and resuscitation. - 1996. - 5. - S. 24-27.

4. Cetlinski S. A. prospects for clinical use of recombinant cytokines. //West. Grew up with. Acad. The honey. Sciences. - 1993. - 2. - S. 11-17.

5. Kozlov C. A., Ostanin, A. A., Leplin O. Y. and others Extracorporally immunotherapy in the correction of "immunoparalysis patients with chirurgiche the mechanisms of therapeutic action and tactics immune. //International J. on Immunorehabilitation. - 1998. - 10. - S. 66-76.

7. Lebedev, P. M., Poltronova Century So Some aspects of the pathogenesis and treatment of multiple organ failure. //Anesthesiology and resuscitation. - 1995. - 2. - S. 83-88.

8. Makarova N. P., Konichiwa I. N. The syndrome of endogenous intoxication in sepsis. //Anesthesiology and resuscitation. - 1995. - 6. - S. 4-8.

9. Nesterov centuries, Belyaev D. L., Kuznetsov, B. N. Using lacenterra in treatment of neonatal sepsis. //Antibiotics and chemotherapy. - 1993. - 1. - S. 62-68.

10. The delegation B. C., Zhumadilov J. W. Syndrome of multiple organ failure in surgery. //Surgery. - 1990. - 7. - S. 158-161.

11. Simbirtsev S. A., Popovic A. M. the Scope of recombinant interleukin-1 in the treatment of patients with immunodeficiency in trauma and sepsis. //Anesthesiology and resuscitation. - 1996. - 4. - S. 76-78.

12. Sorokin A. M., Checknew S. B., Kuznetsov, B. N. Immunomodulating activity of domestic medical natural interferon-. //Immunology. - 1989. - 1. - S. 17-20.

13. Ostriches centuries , Kuznetsov, B. N., Belyaev D. L. et al. Immunomodulation by lacenterra in acute inflammatory diseases of organs of abdominal cavity. //Antibiotics and chemotherapy. - 1992. , 37, 2 is x in patients with multiorgan failure. //Anesthesiology and resuscitation. - 1996. - 1. - S. 75-81.

15. Faist E., Schinrel S., Zimmer S. Update on the mechanisms of immune supression of injury and immune modulation. //World J. Surg. - 1996. - 20 (4). - R. 454-9.

16. Ziegler-Heitbrock, H. W. L. Moleculas mechanism in toleranse to lipopolycacharide. //J. of Inflammation. - 1995. - 45 (1). - P. 13-26.

The method of treatment of patients with multi-organ failure, including the combined therapy and the introduction of lacenterra, characterized in that the injection lacenterra spend 10 thousand IU daily for 10 days, and during the first five days appoint endobronchial introduction lacenterra dissolved in 10 ml of solution, a dose of 10 thousand IU 1 times a day through day course of 3 treatments.

 

Same patents:

The invention relates to medicine, neonatology, and to methods of correction of Central hemodynamics in newborn
The invention relates to medicine, in particular to urology
The invention relates to medicine and relates to a composition having a General tonic, stimulant and radioprotective action

The invention relates to new aryl-S(O)n-substituted carboxylic/hydroxamic acids of formula I, where Y represents hydroxy, XONH-where X is H, C1-C6alkyl; R1means H, C1-C6alkyl; R2means H, C1-C6alkyl, C3-C8cycloalkyl, C3-C8cycloalkyl - C2-C8alkyl, tetrahydropyranyl, piperidinyl, -NR6R7where R6means H, C1-C6alkyl, aryl; R7means H, C1-C6alkyl, aryl, aryl - C1-C8alkyl, -SO2NR8R9aryloxyalkyl, C1-C8alkoxycarbonyl, -C(O)-O-CH2Rdwhere Rdmeans phenyl; or a group NR6R7means valinamide; R8and R9independently mean H, C1-C6alkyl; or R1and R2together with the carbon atom to which they are attached form a C3-C8cycloalkyl or possibly substituted lower alkyl piperidinyl or tetrahydropyranyl; R3means H, C1-C6alkyl, C3-C8cycloalkyl, C3-C8cycloalkyl-C1-C8alkyl, aryl, aryl - C1-C8alkyl, piperidinyl, tetrahydropyranyl; R4means H, C1-C6alche are C3-C8cycloalkyl, R3and R4together represent C3-C8cycloalkyl; R5means aryl, possibly substituted
The invention relates to medicine and relates to tools for parenteral protein nutrition and removal of toxemia

The invention relates to the treatment of endotoxemia caused by endotoxins, in particular to the treatment of poisoning endotoxins introduction into the organism of various compounds that neutralize and/or remove endotoxins from the body, and also to prevent using these compositions
The invention relates to medicine, in particular to radiology, and can be used as a radiopaque contrast agent in the examination of various organs

The invention relates to previously unknown compounds, useful in medical and veterinary practice, to their pharmaceutically acceptable salts and biopremier derivatives, to methods for obtaining data of new compounds, to pharmaceutical compositions containing these new compounds, to a single dosage forms of these compositions and to methods of treating patients using these compositions and dosage forms

Medicinal gel // 2184564
The invention relates to medicine and the pharmaceutical industry and relates to dosage forms containing interferon
The invention relates to medicine, Hepatology, gastroenterology and clinical lymphology, to methods of treatment of chronic viral hepatitis

The invention relates to the field of medicine and relates to pharmaceutical compositions containing the c-kit-ligand and hematopoietic factor, a method of increasing levels of stem cells in the peripheral blood, an antagonist of c-kit ligand, antisense molecules of nucleic acid, the method of increasing levels of peripheral blood cells ex vivo

The invention relates to medicine, in particular to the conjugates of interferon formula I

< / BR>
where R and R', independently of one another, represent lower alkyl; X represents NH or O; n and n' are integers, the sum of which ranges from 600 to 1500; and the average molecular weight parts of polyethylene glycol in the conjugate is from 26000 to 66000 Yes, and to a method for conjugate PEG--IFN with antiproliferative activity, as well as to a method of treatment or prevention immunomodulatory diseases
The invention relates to medicine, namely to Oncology, and can be used for the treatment of patients with non-Hodgkin's lymphoma II-IV stages of the disease

The invention relates to the field of medicine and pharmacology and applies to new effectors of interferon against viruses genital herpes and human papilloma
The invention relates to medicine and can be used in the treatment of concomitant chlamydial herpes infection in women with inflammatory diseases of the pelvic organs (PID)

The invention relates to medicine, Hepatology, to methods of treatment of chronic viral hepatitis
The invention relates to medicine, more specifically to oncourology, and may find application in the treatment of malignant tumors of the kidney with metastases
The invention relates to the venereal diseases and urology, and is intended for the integrated treatment of benign tumors of the urethra associated with urogenital infections

FIELD: medicine, anesthesiology-resuscitation, infectology, detoxication.

SUBSTANCE: the innovation suggested interrupts infectious-toxic shock, moreover, after that it is necessary to prescribe peroral intake of Reaferon-EC-Lipint at the dosage of 10000 - 15000 U/kg. Then one should sample patient's blood to obtain leukocytes to be washed and diluted in 0.9%-NaCl solution, activated due to incubation with immunophan and intravenously injected for a patient. Then comes peroral intake of Reaferon-EC-Lipint at the dosage of 10000 - 15000 U/kg once daily for 5 d. The innovation enables to decrease the number of complications and lethality due to decreasing immunodeficiency.

EFFECT: higher efficiency of therapy.

3 ex, 1 tbl

Up!