RU2462712C1 - Method for determining objective indications for disintoxication therapy in children with infectious diseases - Google Patents

Abstract

FIELD: medicine.

SUBSTANCE: child's blood plasma is examined for the medical concentration of average molecular compounds, as well as the functional state of albumin by the effective concentration of albumin as of the date of admission to hospital. If observing the concentration of average molecular compounds more than 0.260 standard units, and decrease of the effective concentration of albumin less than 35 g/l, the disintoxication therapy is prescribed.

EFFECT: use of the declared method enables higher effectiveness of determining the indications for the disintoxication therapy in the children suffering infectious diseases.

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Description

The invention relates to medicine, in particular to pediatrics, and can be used for infectious diseases in children to determine indications for detoxification therapy.

In children with many infectious diseases, the pathological process, as a rule, quickly leads to profound metabolic disorders, endogenous toxin formation, toxemia and the formation of endotoxemia syndrome. The presence of this syndrome for any infectious pathology often requires the doctor to make a decision on detoxification therapy, which is quite a serious manipulation and is not indifferent to the child’s body, both physiologically and psychologically. Currently, to determine the indications for detoxification therapy, pediatricians rely on the severity of symptoms of endotoxemia and the clinical picture of the disease, but they only reflect subjective changes in the body. Often this leads to an underestimation of the condition of the child, and, accordingly, the choice of the wrong treatment tactics, which reduces the effect of the therapy. To this end, it is necessary to develop objective criteria for detoxification therapy in children with infectious diseases.

Currently, there is a method of determining indications for detoxification therapy in adult patients with endotoxemia syndrome by determining the average molecular compounds in the blood serum formed during the destruction of large protein molecules and cell membranes. Medium molecular compounds are oligopeptides weighing from 500 to 5000 D, which by their nature relate to protein toxins with a high content of carboxylic amino acids, nucleotides, oligosugars, alcohol derivatives. Medium molecular compounds have a direct membrane-toxic effect and initiate the appearance of peptides that are close in structure to bioregulators. 80% of the average molecular compounds are composed of proteins and their metabolites, including products of the hydrolysis of fibrinogen and globulins, the catabolism of glucocorticoids. A number of biologically active substances were found in their composition: bradykinin, parathyroid hormone, neurotoxin X, an inhibitor of glyconeogenesis, inhibitors of DNA synthesis, cell proliferation and blast transformation of lymphocytes, phagocytosis and hematopoiesis, a natriuritic factor and a factor that increases the fragility of erythrocyte membranes. In addition, inhibitors of platelet aggregation, amino acid transport, glucose utilization, hemoglobin synthesis, lactate dehydrogenase activity, lipolysis, and factors leading to dissociation of respiration and oxidative phosphorylation and a decrease in ATP pool are found. These substances determine their toxicity: impaired erythropoiesis, decreased rosette formation, inhibition of mitochondrial respiration, impaired DNA synthesis in hepatocytes and lymphocytes. The neurotoxic effects of medium molecular compounds are associated with the formation of false mediators: they, interacting with insulin, inactivate the hormone, inhibiting phosphorylation, and disrupt energy metabolism in the cell. An increase in the level of average molecular compounds is one of the most sensitive signs of endogenous intoxication. The concentration of average molecular compounds in the blood of children with endogenous intoxication syndrome naturally changes and corresponds to the degree of clinically determined. Their toxicity is provided not by any separate component that appears during pathology, but by a complex of the above substances, despite the fact that most of them are present in the norm. The realization of their toxic properties in the body of children is ensured, firstly, by a large number of medium molecular compounds, and secondly, by a decrease in the plasma antitoxic potential. Accumulating, they contribute to the strengthening of general toxic effects in the child's body by weakening the sorption properties of endogenous albumin [1]. It should be noted that this indicator is most often used in isolation to determine the degree of endotoxemia, mainly in resuscitation and surgery in adult patients [2], [3]. No information was found on the use of secondary molecular compounds in pediatric infectious diseases as a universal criterion for determining indications for detoxification therapy.

The disadvantage of this method is its limited use, only in adults, as well as nonspecificity, since most of the determined parameters are present in the blood of a healthy person.

There is also a method of determining indications for detoxification therapy in adult patients with endotoxemia syndrome by determining the functional state of plasma albumin by toxicity index, albumin binding pool, total albumin concentration. The authors propose using a concentration of “effective” albumin to determine indications for detoxification therapy in children. By "efficiency" is meant the "working capacity" of albumin, its ability to bind toxic substances in specific active centers of its own molecule. The growth of endotoxemia leads to "overload" of the active centers of the albumin molecule with toxic substances, its ability to detoxify, and as a result its concentration decreases. The amount of “effective” albumin in the blood serum is not a specific marker of only the infectious process. This indicator is used as a marker of endotoxemia in other diseases and pathological conditions: the nature of intoxication, its intensity for any pathology determines the rate of breakdown of protein structures. But with infectious diseases, this indicator is also used. Intoxication of the body that arose during many infectious diseases is a factor capable of supporting the first phase of the metabolic reaction, accompanied by a catabolic shift in protein metabolism, and inhibiting the onset of its second, recovery phase. A similar phenomenon is observed in infectious diseases, when the massive influx of toxins into the bloodstream causes a lack of transport capacities to ensure adequate detoxification. Severe forms of infectious diseases against a background of reduced body resistance are accompanied by a decrease in the binding ability of serum albumin [4]. So, in patients with diphtheria, a significant decrease in the binding function of human serum albumin caused by a toxin was revealed, which correlated with the severity of the disease [5]. The concentration of "effective" albumin is a universal method for determining the presence of endotoxemia. Therefore, the authors believe that the concentration of albumin is a specific indicator for childhood infectious diseases, and the authors are entitled to use this indicator to determine objective indications for detoxification therapy in children with infectious diseases. Moreover, in most cases, this indicator serves, as in the case of medium molecular compounds, only to determine the presence and degree of endotoxemia. The authors propose using it as a criterion for determining indications for detoxification therapy. The authors propose to use these indicators together, since they reflect the accumulation in the blood of substances completely different in chemical structure, and also when used together, they can more objectively determine the presence of endogenous intoxication and indications for detoxification therapy.

The disadvantage of this method: previously this method was not used in pediatric practice to justify detoxification therapy, and was also not used in combination with other methods.

There is also a method of determining the indications for detoxification therapy in children with endotoxemia syndrome, based on the data of the clinical picture of the disease and traditional laboratory examination - determining the level of leukocytes and leukocyte blood count. This screening method was adopted as a prototype [6].

The disadvantage of this method: this method allows you to only subjectively determine the indications for detoxification therapy, since it does not allow an objective assessment of the severity of endotoxemia syndrome in patients.

The aim of the invention is the determination of objective indicators for detoxification therapy in children with infectious diseases.

This goal is achieved by the fact that the concentration of average molecular compounds in the serum of venous blood is determined, as well as the functional state of albumin is determined by the effective concentration of albumin and compared with normal values; with an increase in the concentration of average molecular compounds above 0.260.e. and a decrease in the effective concentration of albumin below 35 g / l, detoxification therapy is prescribed.

The method is implemented in the following way: capillary blood is taken from the finger on the 1st day of admission to the hospital and the number of leukocytes and blood cells is counted by traditional methods. Venous blood is also taken for patients strictly medically from the ulnar vein on the 1st day of admission to the hospital. Blood serum is obtained from whole blood by centrifugation or sedimentation. The finished serum is stored in a refrigerator at -15 ° C until testing.

The level of average molecular compounds in blood serum is determined by the screening method in the modification of M.I. Gabrilovich. In this case, 2 ml of heparin-stabilized blood serum is mixed with 2 ml of 1.2 M perchloric acid and centrifuged at 7000 rpm for 20 minutes. 2 ml of the supernatant are separated, 0.4 ml of 2M potassium carbonate is added and placed in the freezer of the refrigerator for 15-20 minutes. The supernatant is separated by centrifugation for 20 minutes, at 2500-3000 rpm. One ml of the supernatant is mixed with 4 ml of 80% rectified ethyl alcohol and centrifuged for 15 minutes at 2500-3000 rpm. 2 ml of the supernatant are diluted with 4 ml of distilled water and the optical density of the substrate is determined on an SF-46 spectrophotometer at a wavelength of 210 nm against distilled water as a blank sample. The result obtained is compared with the control digits.

The measured parameter - the average molecular compounds - are expressed in arbitrary units (cu). Normal indicators are 0.180-0.260 cu

The functional state of serum albumin is studied by the method of fluorescent probes using a K-35 probe. Conformational rearrangement of the serum albumin molecule when it is bound to the K-35 fluorescent probe is directly proportional to the fluorescence intensity. The fluorescence intensity of the K-35 probe is measured on an AKL-01 fluorimeter at an excitation wavelength of 420 nm and an emission wavelength of 530 nm. Results are expressed in units of concentration. Calibration to the value of the effective and total concentration of serum albumin is carried out using simulators of the blood serum composition GSO 6996-91, calibrated to the values of the effective and total concentration of albumin in the NIMVC physico-chemical medicine in Moscow. The value of the total and effective albumin concentration is determined using the probe-Albumin reagent kit in 1 × 1 cm quartz cuvettes. The first measured parameter reflects the total serum albumin concentration and practically coincides with the albumin concentration measured by standardized clinical methods. The second measured parameter is called the "effective concentration of albumin", it depends both on the concentration of albumin and on the structure of its binding centers. By "efficiency" is meant the ability of albumin to bind various toxic substances in specific active centers of its own molecule.

The measured parameter - the effective concentration of albumin - is expressed in grams per liter (g / l). Normal values are 35-55 g / l. These reference values of serum albumin - 35-55 g / l - were taken from the reference manual [7]. Values are given without differentiation for adults and children. Therefore, the selected indicators were obtained empirically in the study of serum albumin in 120 children.

This method was used in 120 children with various infectious pathologies in bacterial and viral infections to determine objective indications for detoxification therapy.

Example 1. Boy T., 4 years old, was admitted to an infectious diseases hospital with complaints of fever up to 38 ° C, sore throat, enlargement of the cervical lymph nodes, snoring breathing at night, lethargy, loss of appetite. From the anamnesis: sick for 4 days, body temperature all days increased no higher than 38 ° C, decreased antipyretic. On day 3, sore throat appeared, cervical lymph nodes increased, nasal congestion appeared, moderate manifestations of endotoxemia in the form of lethargy and decreased appetite. The child was hospitalized and examined in a children's infectious diseases hospital. Diagnosed with Infectious Mononucleosis. In treatment, an antibacterial drug, antipyretic, symptomatic drugs were prescribed, the issue of detoxification therapy was decided. Indications for detoxification were determined by the method selected for the prototype. A general blood test revealed moderate leukocytosis - 10.2 × 10 / l, in the leukocyte formula - a moderate shift to the left - stab neutrophils - 7%. Considering minor changes in the general analysis of blood and unexpressed symptoms of endotoxemia, detoxification therapy, it was decided not to conduct. However, despite the ongoing treatment, the child did not improve, the clinical manifestations of the disease and the symptoms of endotoxemia remained at the same level. Given this, the doctor prescribed a biochemical blood test to determine the concentration of average molecular compounds and the effective concentration of albumin in serum. This analysis showed an increase in the concentration of average molecular compounds to 310 cu, and the effective concentration of albumin was 19 g / l. It was decided to conduct detoxification therapy. After 2 days of detoxification, the child's condition improved: the temperature returned to normal, the boy became active, and he developed an appetite.

Example 2. Girl M., 10 years old, was admitted to an infectious diseases hospital with complaints of fever up to 39 ° C, sore throat. From the anamnesis: 3 days sick, temperature all days up to 38-39 ° C, sore throat. The local pediatrician was diagnosed with SARS. Symptomatic treatment: antipyretic, antiviral drugs. There was no improvement. The child was hospitalized in a children's infectious diseases hospital, examined and examined. Diagnosed with "Lacunar angina." Prescribed treatment: antibacterial, antipyretic drugs, local antiseptics. There were no symptoms of endotoxemia in the clinical picture of the disease. The child was examined by the method selected for the prototype. In the general analysis of blood, moderate leukocytosis is 11.5 × 10 / l, in the leukocyte formula there is a moderate shift to the left - stab neutrophils - 6%. As a result of the examination and examination, it was decided not to carry out detoxification therapy. However, despite the treatment, the child developed weakness, lethargy, and decreased appetite. A biochemical blood test was prescribed by the attending physician to determine the concentration of average molecular compounds and the effective concentration of albumin in serum. This analysis showed an increase in the concentration of average molecular compounds to 410 cu and a decrease in the effective concentration of albumin to 11 g / l. It was decided to carry out detoxification. After 3 days of detoxification therapy, the girl's condition improved.

Thus, the values of the concentration of average molecular compounds and the effective concentration of albumin in blood serum can be used as objective indications for detoxification therapy in children with infectious diseases in infectious pediatric hospitals and departments of hospitals.

Information sources

1. Uchaykin V.F., Dairy V.P. Infectious toxicosis in children. - M.: Publishing House of the RAMS, 2002. - 61-69 p.

2. Anesthesiology and intensive care. Edited by O.A. Dolina. M .: Medicine, 2002

3. Belyakov N.A., Malakhova M.Ya. Criteria and diagnosis of endogenous intoxication // Endogenous intoxication: Abstract. doc. Int. symp - SPb. - 1994 .-- S.60-62.

4. Alba D.V. Pathophysiological aspects of endogenous intoxication in children in the acute phase with infectious diseases // Diss. ... cand. honey. sciences. - Saransk, 1998.

5. Zhukova L.I. The binding ability of serum albumin in patients with diphtheria // Clinical laboratory diagnostics. -1999. - No. 5.

6. Obolensky S.V., Malakhova M.Ya. Laboratory diagnosis of intoxication in the practice of intensive care. SPb., 1993.

7. Clinical laboratory tests from A to Z and their diagnostic profiles. Ref. allowance / B.C. Kamyshnikov. - M.: MEDpress-inform, 2005. - P.20.

Claims (1)

The method of determining indications for detoxification therapy in children with infectious diseases, including capillary blood sampling and determination of the level of leukocytes and blood cells in it, characterized in that the concentration of average molecular compounds is determined in the serum of venous blood, and the functional state of albumin is determined by effective albumin concentrations and compared with normal values; with an increase in the concentration of average molecular compounds above 0.260.e. and a decrease in the effective concentration of albumin below 35 g / l, detoxification therapy is prescribed.