RU2331882C1 - Method of endogenous intoxication severity evaluation in urgent abdominal pathology in early post-operative period - Google Patents

Abstract

FIELD: medicine.

SUBSTANCE: method is applied to clinico-biochemical testing of antioxidant and oxidant blood systems on standard hematological and clinico-biochemical tests background. The results are processed using mathematical criterion that allows evaluation of separate parameters contribution in patient's metabolic dysfunctions. The invention enables to more reasonable characterise endogenous intoxication by aggregate contribution of separate parameters in patient's metabolic dysfunctions, and serves as completion phase in demonstrative clinico-biochemical evaluation of endotoxicosis in urgent abdominal pathology cases.

EFFECT: increase in accuracy and objectiveness of the method.

2 cl, 10 tbl, 1 ex

Description

Application area

The invention relates to medicine, in particular to clinical biochemistry, and is intended to assess the severity of endogenous intoxication in emergency abdominal pathology in the early postoperative period by biochemical research and processing of its results using mathematical criteria to evaluate the totality of the contributions of individual parameters to metabolic disorders in patients .

State of the art

Currently, various methodological approaches to clinical and biochemical monitoring of the severity of endogenous intoxication in patients with emergency conditions have been developed, involving the use of scales and calculation criteria. To characterize the condition of patients with abdominal pathology, various scale systems are used. The scale system involves a numerical assessment of clinical, physiological, laboratory and biochemical parameters. The presence of clinical symptoms or a deviation of a physiological or biochemical parameter from the norm is determined by the number, and the values related to one patient are summarized in a common scale. The resulting number corresponds to a specific diagnosis or severity of the course of the disease [1, 2, 3, 4, 5].

According to [6], an integral and quantitative assessment of the severity of a systemic inflammatory reaction in purulent-septic pathology involves the use of two types of scales:

1) scales for assessing the condition of patients, for example, APACHE, SAPS (the goal is prognosis, the result is an assessment of the risk of death);

2) scales for assessing multiple organ dysfunction, for example MODS, SOFA (the goal is a description of the syndrome, the result is an assessment of the complication).

In [7], it was proposed to classify systems for assessing the severity of the condition of patients with a surgical profile with sepsis into three groups:

1) methods based on the collection of objective clinical and laboratory data (APS; SAPS; APACHE I, II, III; SOFA);

2) methods based on statistical modeling - the MRM system;

3) systems that assess the severity of the condition of patients by the number and complexity of the research and treatment methods necessary for its management - the TISS system.

The use of objective systems-scales for determining the severity of the condition of patients allows us to predict the outcome of the disease and optimize treatment tactics.

However, in accordance with existing scale systems for assessing the severity of the condition of patients with abdominal pathology in emergency conditions, it is necessary to determine a fairly extensive number of clinical and laboratory tests, which often causes objective difficulties in their use in modern conditions due to the lack of necessary equipment, reagents, etc.

In addition, in the literature available to us, we did not meet the scale for assessing endotoxemia in patients with emergency abdominal pathology. In practice, as a rule, only design criteria of the index type are applied.

With peritonitis, the Mannheim Peritoneal Index (MIP) has received international recognition in assessing the severity of the condition of patients. However, this criterion is not an indicator characterizing the degree of endogenous intoxication, which largely determines the outcome of the disease with diffuse peritonitis [8].

One of the calculated indicators characterizing the severity of endotoxemia are leukocyte intoxication indices (LII). The use of LII allows you to evaluate the activity of inflammatory processes. The most widely used LII are Kalf-Kalif, Ostrovsky and Khimich. Their calculation is carried out as follows [27]:

1. LII according to Kalf-Kalif = [(seg + 2yun + 3pal + 4miel) × (pl + 1)] / [(mo + li) / (eos + 1)].

2. LII Ostrovsky = (her + PL) / (mo + whether + eoz).

3. LII according to Khimich = [0.1 lei (thousand) henna (in%)] / [100th].

4. Nuclear shift index = (yun + pal + myel) / seg.

According to [9], the advantage of the Kalf-Kalif LII is the ability to convert hemograms into numerical indicators that reflect endogenous intoxication, including sepsis, peritonitis, purulent acute pancreatitis and cholecystitis. High leukocytosis and an increase in LII according to Kalf-Kalif to 10 is a sign of septic shock. KII-KALIF LII is characterized as a simple, affordable and quite informative indicator. The authors note that the use of this parameter alone does not give a complete assessment of the degree of endotoxemia, but reflects mainly the degree of the inflammatory response of the body.

Along with the foregoing, it should be noted: the principles, guidelines and forms for developing scale systems and design criteria are methodologically justified from the standpoint of evidence-based medicine. Their analysis allows us to propose a very universal approach to deriving a scale system for assessing the biochemical manifestations of endotoxemia in patients with abdominal pathology in emergency conditions based on their real capabilities of clinical express laboratories.

At the stage of putting into practice evidence-based evaluative clinical and biochemical approaches to studying the metabolism of the body of surgical patients with abdominal pathology in emergency conditions, one of the most common forms is the use of index parameters. Analysis of the indices for assessing the severity of endogenous intoxication and the condition of patients presented in the literature allows us to highlight the following features of their elimination.

To build index dependencies, marker tests of biochemical, hematological, clinical and biochemical orientation are selected.

A known method for diagnosing the severity of endogenous intoxication in acute purulent-septic diseases in children (RF patent No. 2122739) by electrophoretic research, characterized in that the blood serum is examined and if there are protein components on the electrophoregram with mol. m. less than 12 to Yes, severe endogenous intoxication is diagnosed with the formation of organ failure.

The disadvantage of this method is that not every laboratory has the technical capabilities for conducting an electrophoretic study, it is quite long (on average, the analysis time will be about 8-9 hours).

A known method for assessing endogenous intoxication of the body (RF patent No. 2082971) by studying and counting the formed elements of peripheral blood, characterized in that they examine red blood cells and determine the index of intoxication of AI according to the formula, which includes the number of echinocytes, poikilocytes, hemolytic forms, discocytes, stomatocytes.

This method is also complicated in execution, which is its disadvantage.

A known method for the diagnosis of endogenous intoxication in severe mechanical trauma (RF patent No. 2195652) by blood counts and scores of the shock morbidity of trauma, characterized in that they measure the chemiluminescence of whole blood and the chemiluminescence of a population of monocytes and determine the index of intoxication of AI according to the formula, which includes a shockness score ; chemiluminescence of whole blood and monocytes induced by zymosan, mV.

The method requires the use of expensive reagents (including zymosan), the chemiluminescence method can not be carried out in every diagnostic laboratory due to the lack of the necessary laboratory equipment - all this can be considered its disadvantages.

A mathematical expression that serves as one or another calculated index can be a ratio of parameter values (or their group) to each other, as a rule, in the case of a mutually directed action, a sum or a product, most often in the case of a unidirectional action or, if necessary, emphasize the ratio of indicators to analysis of one biological fluid. In this case, the advantage of using indices is the ease of calculation.

A known method for determining the oxidant / antioxidant activity of a solution of an analyte (application of the Russian Federation No. 2002130523), comprising evaluating the oxidant / antioxidant activity by electrochemical parameters of a solution of an analyte, characterized in that the initial solution is preliminarily prepared, into which a mediator system containing simultaneously oxidized and reduced is introduced form of the reagent, and the assessment of oxidant / antioxidant activity is carried out by changing the redox potential of the a thief identified before and after introducing into the stock solution of the analyte. The concentration (activity) of oxidants / antioxidants in solution is calculated by the formula as the ratio of the concentration of the oxidized form of the mediator to the concentration of the reduced form of the mediator.

This method requires the use of reagents that are not available in every laboratory, including due to their high cost, as well as the necessary measuring equipment, which can be considered disadvantages of the method.

A known biochemical method for determining endogenous intoxication [14], which consists in determining the level of medium-weight molecules in blood serum. Middle-weight molecules are an integral biochemical marker of endogenous intoxication [15].

This method involves fasting blood, separating serum from blood cells by centrifugation, obtaining a protein-free sample by adding 0.5 ml of 10% trichloroacetic acid to 1 ml of blood serum and centrifuging for 30 minutes at 3000 rpm. Next, 4.5 ml of distilled water is added to 0.5 ml of the supernatant and the optical density of the sample is determined on a spectrophotometer at a wavelength of 254 nm. The content of medium-weight molecules is determined by the optical density of the sample and the presence of endogenous intoxication is judged by their level.

However, this method is quite long in execution (centrifugation is carried out within 30 minutes) and requires a large amount of blood serum (1 ml), which is necessary for conducting a study, which is not always possible to obtain from a patient, especially in the practice of express laboratories in intensive care and intensive care units when the clinician has a question about choosing the necessary complex of laboratory tests, which limits the application of this method.

The prior art method for determining endogenous intoxication (RF patent No. 2193780), including blood sampling, separation of serum from blood cells, deproteinization, centrifugation, addition of 4.5 ml of distilled water to 0.5 ml of supernatant, spectrophotometry of the sample at a wavelength 254 nm and diagnostics according to the level of medium-weight molecules, characterized in that prior to deproteinization, blood serum is diluted 10 times with physiological saline, the sample is centrifuged for 10 minutes and with a value of more than 0.136 optical units tion density judged on the presence of endogenous intoxication in patients.

This method characterizes only the level of medium-weight molecules in the blood - this is a pool of substances of various origins (including products of lipid peroxidation) - and does not allow us to evaluate the contributions of various substances that make up the pool to the formation of endotoxemia, which can be considered disadvantages of the method. In [10], the special value of assessing the balance of LPO and AOS reactions was noted, the degree of which can be determined by the value of the integrated imbalance coefficient (K) in the LPO / AOS system:

K = [(DK _i / DK _n ) · (MDA _i / MDA _n ) · (СО _i / СО _n )] / [(TF _i / TF _n ) · (CPU _i / CPU _t )],

where DC are diene conjugates, MDA is malondialdehyde, CO is the degree of oxidation of blood lipids, TF is α-tocopherol, CP is ceruloplasmin, designations with index i correspond to the test sample, and designations with index n correspond to the average value in normal.

This method of assessing the balance of LPO and AOS reactions using the appropriate index includes the determination of substances of various levels of the SRO reaction cascade in combination with the activity of antioxidants: this is the positive side of the method. However, in a conventional clinical laboratory it is difficult to identify all the components of the integrated imbalance coefficient (K) in the LPO / AOS system due to the need for expensive reagents and equipment: this is a disadvantage of the method.

In acute pancreatitis, an endogenous intoxication index (IEI) was proposed and tested [11] for the following parameters: the level of total blood protein B (g / l); urea M (mmol / l); substances of medium molecular weight peptide nature of MSM (according to Lowry); Alanine aminotransferase AlAT (mmol / h · l):

.

.

The disadvantage of this endogenous intoxication index (IEI) is the following: the calculation formula includes parameters that have different units of measurement. In this case, the conversion of the values of the used clinical and laboratory tests to relative values is required, for example, by dividing the value of each indicator by its norm (in this case, the units are reduced).

As constituent indices, one or another regression or correlation dependence of the studied criteria can be taken. In this case, more relevant is the greater correspondence of the obtained mathematical expression to the real characteristics of the variational series.

In [12], a number of intoxication indices were proposed.

Intoxication Index 1, which includes indicators of protein catabolism, functional activity of the liver, the number of leukocytes and lymphocytes in the blood and reflects such an organism function as detoxification. An intoxication index 2 was used to evaluate the state of the peripheral blood formula. The state of antioxidant status in the blood and the level of the transport function of albumin characterizes the intoxication index 3. The intoxication index 4 combines the parameters included in intoxication indices 2 and 3.

The calculation of intoxication indices (Y or II) was based on the formula proposed by M.N. Tarelkina [13]:

where Ap are the real values of the ith sign, An is the average value of the ith sign in donors, δ is the variance of the ith sign in donors.

An interval estimate of the approximate values of intoxication indices with a one-sided confidence probability (t _β ) with reliability β = 0.95 was carried out according to the following formulas:

II _max = M + ε,

where t _β is the value that determines the number of standard deviations that need to be postponed to the right or left of the scattering center (with a one-sided confidence probability) so that the probability of a random variable X falling into the obtained interval is equal to β (t _β values are taken from the corresponding distribution tables Student).

Since some factors are associated with a significant and even strong correlation dependence, the calculation of the total (total) variance was carried out according to the formula

These indices can be considered analogues of the proposed method. However, they also have a number of drawbacks: the calculation of the corridor of values of the magnitude of the indices is carried out only in the direction of the maximum, the minimum values of the indices are not calculated; it is necessary to calculate the correlation of parameters, which takes time to recruit a group of examined people.

The objective of the invention is to offer a comprehensive system for assessing the development of endogenous intoxication in patients with emergency abdominal pathology based on the study of the ranges of changes in the studied blocks of hematological and clinical-biochemical tests and the development of a methodological approach for deriving calculated indices characterizing the degree of balance of the studied metabolic chains.

The technical result of the invention consists in the fact that the method allows to characterize endogenously intoxication more conclusively by the combined contribution of individual parameters to metabolic processes in the patient’s body, serves as the final step in applying the methodology of evidence-based clinical and biochemical evaluation of endotoxemia in patients with emergency abdominal pathology.

This method allows you to use the mathematical criterion J in the express laboratories of the intensive care unit, with a short analysis time, but the need to comprehensively assess the severity of endogenous intoxication with emergency abdominal pathology.

The method is suitable both for a single study and for monitoring the severity of endogenous intoxication in patients with abdominal pathology in the early postoperative period.

Achievement of a result

This technical result is achieved due to the fact that the method for determining the severity of endogenous intoxication in case of emergency abdominal pathology in the early postoperative period, including blood sampling, clinical and biochemical studies of the parameters of the antioxidant and oxidative systems in the blood against standard hematological and clinical biochemical tests, differing the fact that they use calculated indices to identify the degree of balance of the oxidative and antioxidant systems in the blood, determined by following formula:

причем параметр_{больного} характеризует параметр, полученный по данным исследований больного, а параметр_норма характеризует параметр, полученный как среднее арифметическое по данным исследований у здоровых людей.

moreover, the _patient parameter characterizes the parameter obtained according to the patient’s research, and the _norm parameter characterizes the parameter obtained as the arithmetic mean according to the research data in healthy people.

Then, the mathematical criterion J is calculated, which characterizes the set of contributions of individual parameters in violation of the metabolic processes in the patient’s body in accordance with the formula in blocks of the analyzed tests in accordance with the formula:

,

,

where Δ _n is the deviation of the n-measurement of the mathematical expectation of the patient’s magnitude, corresponding to the contribution of each test to the total index J, and J is represented as a range of values J _min -J _max , and Δ _{n is} calculated by the formulas for the variation series:

for the minimum value parameter contribution to the total index J _min:

Δ _n = (M-m normal) - (M-m in the group of examined);

for the maximum value of the parameter contribution to the total indicator J _max :

Δ _n = (M + m normal) - (M + m in the group of patients).

The calculation of M and m is based on variation statistics for small samples using Student's t-test:

To estimate the mathematical expectation (M), the values of I, where M and m are variation statistics for small samples using the t - Student criterion and are determined by the formulas:

,

,

where δ is the standard deviation, determined by the formula:

, где

- среднее значение величины I_i - определенного значения выборки.

where

- the average value of I _i - a certain value of the sample.

To calculate the total criterion J for a particular patient, the data of the clinical and biochemical examination for each of the parameters are compared with the mathematical expectation or with the average value of this parameter in the control group (norm), i.e. Δ _{n is} calculated as the difference between the value of the indicator M in norm and the value of the parameter in the patient during this observation period - this is the value corresponding to the contribution to the total indicator J of each test.

To determine the confidence coefficient (accuracy measure t) when testing the hypothesis about the equality of the arithmetic mean M ₁ and M _{2 of} parameter I in any two groups of the examined, the following formula was used:

It should be noted that criterion J is most indicative of complex use, although it can be adapted to the list of applied clinical and biochemical parameters in a particular clinic. The calculation of the contributions of individual blocks of indicators to the total criterion J, in addition to the need to take them into account in accordance with the formula, allows a comprehensive interpretation of the revealed metabolic disturbances in the patient's body in the early postoperative period. For example, with cholecystitis, more than 90% of the contribution to the minimum value and about 90% of the contribution to the maximum value of the total criterion J is made by the values of J according to the block of biochemical parameters (indicators of free radical oxidation and antioxidant protection, the level of molecules of average weight) and the binding ability of albumin. In this case, there is a predominance of the contribution to the value of the total criterion J of the values of J in the binding ability of albumin (up to 69%). With diffuse peritonitis of the reactive and toxic stages with a favorable outcome of the disease, the picture is similar. However, on the 3rd and 5th day of observation, it is noted that with diffuse peritonitis of the toxic stage, a significant contribution to the total criterion J is also made by the block of hematological and clinical-biochemical parameters. With diffuse peritonitis of the terminal stage and with an unfavorable outcome in the early postoperative period, this trend intensifies. So, on the 5th day after the operation, with diffuse peritonitis of the terminal stage, 37.8% of the contribution to the total criterion J falls to the contribution of the block of hematological parameters, and with an unfavorable outcome of spilled peritonitis, 39.2%.

All this allows us to conclude that it is preferable to use the entire complex of components of the total criterion J to assess the severity of endogenous intoxication in the early postoperative period.

If the values of the total criterion J correspond to the values of this total criterion for certain diagnoses (chronic and acute cholecystitis, diffuse peritonitis), detected by comparison with the values calculated by us in the examination groups, the severity of endogenous intoxication of the body corresponding to these nosologies is noted.

For predicting the outcome of diffuse peritonitis, the most significant ranges are J on days 1 and 3 of the postoperative period, which showed borderline changes depending on the stage and outcome of the disease. The values of the total criterion J with diffuse peritonitis on the 1st day after surgery in the range of 9937.56-14454.89, on the 3rd day - in the range of 8955.13-9350.07 indicate a risk of an unfavorable outcome of the disease. At the same time, on the 5th day of observation, the range of the total criterion J (10151.85-11816.29) in deceased patients overlapped with that in patients with diffuse terminal stage peritonitis (11445.87-12491.55). This may indicate that the 5th day of the postoperative period is a critical stage in the observation of patients with diffuse peritonitis of the terminal stage.

Given that in different clinics there are biochemical laboratories of various levels of equipment and, perhaps, not in each of them it will be possible to determine the entire spectrum of tests used in our work, correction of the J ranges can be carried out in accordance with a specific list of determined endotoxicosis markers. In addition, in clinical biochemistry it is customary, when testing analysis methods, to determine standard values and compare them with the indicated values in the methods in each laboratory independently, since there may be slight differences in the results, for example, due to the use of different measuring equipment.

The novelty of the method is its complexity and versatility: if necessary, the mechanism for calculating criterion J can be applied to such a group of biochemical indicators that are used in this express laboratory.

SUMMARY OF THE INVENTION

The following basic requirements for scale systems are defined by the principles of evidence-based medicine:

- methodological validity;

- objectivity;

- clinical efficacy.

In accordance with these principles, the main methodological methods for deriving scale systems can be considered:

- the study of the theoretical premises of their development in accordance with the historical logic of the development of science;

- study of the advantages and disadvantages of existing systems for assessing the severity of the condition of patients;

- analysis of possible directions for improving existing scales or developing new ones.

Given the above principles and methods for developing scale systems for assessing the severity of endotoxemia in patients with abdominal pathology in emergency conditions, the forms of their presentation can be as follows:

1) tables of ranges of changes of the studied test blocks with a point scale for their assessment;

2) calculated indices characterizing the degree of balance of the studied metabolic chains;

3) integrated systems, including items 1 and 2 as components.

In connection with the objective difficulties of using the existing scale systems for assessing the severity of abdominal pathology based on their use as a theoretical and methodological basis, an author scale system for monitoring the biochemical manifestations of endotoxemia in emergency conditions was developed.

Our proposed scale system can be classified as complex:

- based on the registration of the contributions of individual blocks of the tested tests (hematological and clinical-biochemical) and the derivation of the calculated indices of marker parameters of the severity of endogenous intoxication;

- provides for the analysis of a complex mathematical criterion, which characterizes the set of contributions of individual parameters in violation of metabolic processes in the patient’s body by the blocks of the analyzed tests.

The advantage of this scale, in comparison with existing scales, is the possibility of using individual components without reducing the prognostic value, although its use in the system is more justified and effective. Moreover, a promising feature of this scale is the developed ranges of cumulative deviations from the norm in the dynamics of observations of the studied hematological and clinical-biochemical tests, as well as a number of calculated indices (1, 3, 5 days after the operation period).

The proposed scale system for assessing endogenous intoxication, presented in the form of ranges of values of the mathematical criterion J, which characterizes the set of contributions of individual parameters to metabolic processes in the patient’s body by the blocks of the analyzed tests, correlated with the MPI - Mannheim Peritoneal Index - and LII.

Thus, the standards of this scale for its individual components are applicable for assessing the biochemical manifestations of endotoxemia in patients with abdominal pathology in emergency conditions. However, the universality of the development approach, in the absence of the ability to determine the number of tests included in it, makes it easy to adapt this scale to the needs of practice, including considering the possibility of its use in other types of emergency conditions.

Emergency conditions are accompanied by metabolic disorders of varying severity. At the same time, intermediate and final products of normal and impaired metabolism accumulate in body fluids and tissues in non-physiological concentrations, which have a toxic effect and cause dysfunction of various organs and systems.

Among a wide range of metabolites with the ability to exert a toxic effect, a special place is occupied by a pool of substances of medium molecular weight, the dynamics of which reflect the severity of endogenous intoxication. Another factor that can significantly affect the development of endotoxemia is the intensification of free radical oxidation. Therefore, the complex of biochemical studies necessary for the presented scale for assessing endogenous intoxication included an analysis of the parameters of the corresponding metabolic blocks.

The inventive method is as follows

A complex of biochemical studies is carried out, including the study of the parameters of the antioxidant and oxidative systems in the blood, comparing the data with hematological and clinical-biochemical tests, assessing the level of endotoxemia using calculated indices.

The following unified methods for the analysis of the antioxidant system and the severity of oxidative processes in the blood are used:

- total antioxidant and oxidant - OAA and OOA, respectively - activity is evaluated according to [35];

- the activity of ceruloplasmin is evaluated according to [27];

- the level of malondialdehyde - MDA - in the blood is evaluated according to [36].

The severity of endotoxemia in the examined patients in the postoperative period is also evaluated with the calculation of mathematical indices. We proposed these indices because of the need to analyze the ratio of the activity of the constituents of the antioxidant system in blood plasma and red blood cells, as well as the oxidative and antioxidant systems in the blood.

In some cases, the units of measurement of clinical and biochemical parameters are different (for example, plasma OAA -%, ceruloplasmin - mg%). Therefore, it is necessary to introduce K coefficients to obtain relative indices: the value of each parameter must be divided by its norm.

For clinical and biochemical parameters that have the same units of measurement, the introduction of K coefficients is not necessary. However, to achieve uniformity, the coefficients K are introduced in all indices.

Estimated indices reflecting a possible imbalance in the activity of antioxidant system indicators

The human body has both a system for generating active oxygen species (ROS) and a fairly effective system of protection against their damaging effects on intact cells.

In erythrocytes, enzymatic and spontaneous mechanisms of generation of reactive oxygenating radicals (POPs) take place, which are eliminated mainly by specific enzymatic reactions that play a leading role in the initiation of hemoglobin oxygenation processes [16, 17].

It is believed that the blood ROS cytotoxicity manifests itself mainly to red blood cells, which leads to an increase in the content of methemoglobin, the initiation of lipid peroxidation, and hemoglobin serves as a mediator of the formation of hydroxyl radicals.

According to [18], the primary factor causing damage and subsequent elimination of red blood cells is a long-term increase in the intensity of LPO processes in the period 1-3 days of the postresuscitation period.

Given the above, it is important to study the ratio of the total antioxidant activity of plasma and red blood cells to assess the balance of the reactions of antioxidant factors of these biological substrates.

On the basis of this, the introduction of K coefficients is proposed, intended to obtain relative indices: the value of each parameter should be divided by its norm, since the units of measurement of clinical and biochemical parameters can be different.

For example, it is required to develop an index reflecting a possible imbalance of biochemical parameter 1 and indicator 2. Then, the proposed calculated indices can be represented in the form of the following general formula:

где величина

where is the value

Accordingly, the general formula of the proposed calculated indices:

характеризующий возможный дисбаланс ОАА плазмы и эритроцитов и рассчитывающийся таким образом, что берут среднее значение нормы (математическое ожидание величины) ОАА плазмы и ОАА эритроцитов и перемножают на данные ОАА плазмы и ОАА эритроцитов больного.We proposed index 1:

characterizing a possible imbalance of plasma and red blood cell OAA and calculated in such a way that they take the average normal value (expected value) of the plasma OAA and red blood cell OAA and multiply the patient's plasma and OAA data by OAA.

For example, if the average normal value (the mathematical expectation of the value) of the plasma OAA is 13%, and the OAA of red blood cells is 40.78%, then index 1 is determined by the following formula:

A number of proteins, primarily ceruloplasmin, play the role of antioxidants in blood serum. In addition to its antioxidant function, ceruloplasmin controls the synthesis of hemoglobin and a number of other iron-containing proteins, and is also involved in the inactivation of excess hormones in the blood. Protein is produced in the liver and, with an increase in blood peroxides and other lipid peroxidation products, the synthesis of ceruloplasmin and its excretion into the bloodstream is intensified.

Ceruloplasmin has a pronounced oxidase activity; in plasma, it also limits the release of iron stores, activates the oxidation of ascorbic acid, norepinephrine, serotonin and sulfhydryl groups, and also inactivates reactive oxygen species, preventing lipid peroxidation. For more effective protection of red blood cells from free radicals, special receptors are available on the cell surface that can bind ceruloplasmin [19]. The proportion of ceruloplasmin activity in plasma OAA can be estimated using index 2, calculated by the following formula:

For example, if the average normal value (the expected value) of the plasma OAA is 13%, and the activity of ceruloplasmin is 27.15 mg%, then index 2 is derived by the following formula:

Estimated indices reflecting a possible imbalance in the activity of indicators of oxidative and antioxidant systems

Activated forms of oxygen (ROS) initiate the intensification of free radical processes in the tissues and organs of a patient in critical conditions of any genesis. The main types of ROS are initially normal components of cellular metabolism and perform certain biological functions. Their reactive aggressiveness is restrained by the antioxidant system (AOS) present in any living organism, but under pathological conditions this balance is disturbed towards the uncontrolled generation of reactive oxygenating radicals (POP), which leads to the formation of oxidative-antioxidant imbalance in the development of endotoxemia.

The imbalance of plasma OAA and plasma OAA and red blood cells respectively reflect indices 3 and 4.

Index 3 is determined by the formula:

For example, if the average value of the norm (the mathematical expectation of the value) of the plasma OAA is 11.86%, the plasma OAA is 13%, then index 3 is determined by the following formula:

Index 4 is determined by the formula:

The coefficient K = 3.44 for index 4 is obtained as follows.

The average value of the norm (the mathematical expectation of magnitude) of the plasma OAA is 11.86%, erythrocyte OAA is 40.78%.

Then index 4 is derived by the following formula:

Activation of lipid peroxidation (lipid peroxidation) processes leads to the accumulation of toxic products that adversely affect cell membranes. FLOOR is a multi-stage process.

Various metabolites of this cascade of reactions in the disorders of homeostasis occurring during endotoxicosis can play a different role. Diene conjugates are short-lived products, and Schiff bases are chemically inert, therefore, it is believed that their role in impaired cellular metabolism is small, mainly they act as markers of LP activity. In contrast, malondialdehyde (MDA) is not only an indicator of the activity of free radical reactions, but also has toxic properties, since it can damage proteins, enzymes, and nucleic acids [20]. Perhaps, therefore, the excessive accumulation of MDA significantly aggravates endotoxemia [21, 22].

MDA is known to actively interact with serum albumin and erythrocyte and liver proteins [23].

Activation of free radical oxidation processes in the body, observed in many diseases, can significantly affect the functional activity of serum albumin. On the other hand, albumin itself is considered a component of the body's antioxidant system [24, 25]. Albumin reduces the formation of hydroxyl radicals in a system containing copper ions and hydrogen peroxide. This is due to the fact that copper ions bound at high affinity centers become inaccessible to the action of hydrogen peroxide or organic hydroperoxides [26]. It is characteristic that the intensity of LPO processes is disturbed in many pathological conditions, accompanied by endogenous intoxication of the body. LPO processes are not specific and their assessment must be carried out in conjunction with an assessment of the activity of the body's antioxidant defense system.

и индекс 6

The ratio of the concentration of the final products of lipid peroxidation and OAA of plasma and red blood cells, respectively, characterize the index 5

and index 6

The coefficient K = 5.06 for index 5 is obtained as follows.

The average value of the norm (the expected value) of the blood MDA 2.57 μmol / l, OAA plasma 13%.

Then index 4 is derived by the following formula:

The coefficient K = 15.87 for index 6 is obtained as follows.

The average value of the norm (the mathematical expectation of the value) of the blood MDA 2.57 μmol / l, OAA of red blood cells 40.78%.

Then index 4 is derived by the following formula:

Index characterizing the ratio of the levels of molecules of medium weight and malondialdehyde

Molecules of medium weight, according to the classification of M.Ya. Malakhova (1994), consist of 2 groups of compounds - substances of low and medium molecular weights (HV and SMM) and oligopeptides (OD) having a molecular weight of less than 10 kDa.

BH and SMM contain creatinine, urea, oligosugar, lactic acid, bilirubin, amino acids, cholesterol, lipid peroxidation products and other compounds. OP include regulatory peptides (neurotensins, somatostatin, vasoactive intestinal peptide, enkephalins, and other biologically active substances) and non-regulatory peptides (products of proteolytic degradation of plasma and tissue proteins that enter the bloodstream as a result of autolysis, ischemia, organ hypoxia, proteolysis processes) .

The compounds listed above are physiological components, combined into the concept of "medium-mass molecules." Pathological components are products of uncontrolled proteolysis and destruction of organs and tissues, microbial toxins, hydroperoxides, polyamines, as well as increased concentrations of physiological components. The accumulation of a large concentration of medium-weight molecules and the violation of their distribution between plasma and red blood cells, as well as the violation of their elimination by the kidneys caused by various etiological factors, lead to the development of endogenous intoxication of the body [27].

It is believed that the lipid fraction, the value of which correlates with the severity of the patient’s condition, contributes significantly to the toxicity of the MSM pool [28].

In this regard, literature data are of interest, indicating a certain involvement of blood MSM in the regulation of lipid peroxidation [29, 30, 31]. At the same time, the ambiguity of the influence of MSM on in vitro LPO processes (both antioxidant and prooxidant effects) was shown.

The studies of the dynamics of MSM and changes in the activity of lipid peroxidation in various diseases have been the subject of work that proved the role of SRO in the formation of endogenous intoxication, including acute diffuse peritonitis [32] and sepsis [33].

High informativeness of determination of lipid peroxidation products for diagnosis, prognosis of complications of sepsis, and monitoring the effectiveness of its therapy is noted.

.The ratio of the level of MSM to the concentration of end products of LPO is reflected in index 7:

.

The coefficient K = 18.36 for index 7 is obtained as follows.

The average value of the norm (the mathematical expectation of magnitude) MSM 0.14 units opt.pl., blood MDA 2.57 μmol / L.

Then index 7 is derived by the following formula:

.

.

To highlight evidence of biochemical characteristics of the severity of endogenous intoxication, two series of observations of the dynamics of the studied parameters were carried out:

1) 1st series - in the group of patients with abdominal pathology without purulent-septic complications in the early postoperative period, which was composed of patients with cholelithiasis. This series of observations provided a comparison of the ranges of changes in the studied tests in patients with cholelithiasis with chronic cholecystitis (study group 1) and acute cholecystitis (study group 2);

2) 2nd series - in the group of patients with diffuse peritonitis. This series of observations aimed at studying the intensity of disturbances in the dynamics of the studied parameters depending on the stage and outcome of the disease with diffuse peritonitis (study group 3).

Changes in the analyzed parameters in the studied group 1 served as background values for determining the degree of manifestations of violations of biochemical parameters of free radical oxidation and antioxidant protection in comparison with changes in the level of molecules of average mass and calculated indices for assessing endogenous intoxication during surgical trauma in patients with abdominal pathology in the early postoperative period.

In monitoring the block of biochemical indicators of free radical oxidation and antioxidant protection in comparison with the level of medium-weight molecules in the early postoperative period with cholelithiasis with chronic and acute cholecystitis, the informativeness of a comprehensive assessment of their dynamics trends is shown, including through the use of a number of calculated indices.

A comparative analysis of the studied parameters on the 1st day after the operation in the studied groups 1 and 2 revealed marker tests of the severity of endotoxemia. In relation to study group 1, study group 2 was characterized by:

был ниже в 1,7 раза;- on 1 day of observation - a decrease in plasma OAA by 1.2 times and an increase in ceruloplasmin activity by 1.3 times, the coefficient

was 1.7 times lower;

был выше в 1,4 раза;- 3 days after surgery - a decrease in the concentration of MDA in the blood by 1.2 times, the index

was 1.4 times higher;

был ниже в 1,4 раза, индекс

был выше в 1,3 раза.- on the 5th day of observations - a decrease in the concentration of MDA in the blood and OA by 1.2 times, the coefficient

was 1.4 times lower, the index

was 1.3 times higher.

The results of comparing changes in biochemical parameters and their calculated indices can be interpreted as follows:

показывает увеличение доли активности церулоплазмина в ОАА плазмы;- for 1 day of observation - coefficient

shows an increase in the proportion of ceruloplasmin activity in plasma OAA;

отражает увеличение дисбаланса в соотношении уровня МСМ и концентрации конечных продуктов ПОЛ;- on the 3rd and 5th day after the operation - the index

reflects an increase in the imbalance in the ratio of the level of MSM and the concentration of end products of LPO;

характеризуют некоторое нарушение соотношения концентрации конечных продуктов ПОЛ и ОАА эритроцитов. Сравнительный анализ расчетных индексов по биохимическим параметрам в исследуемых группах 1 и 2 может служить подтверждением большей выраженности характеристик эндогенной интоксикации биохимического мониторинга в исследуемой группе 2, по сравнению с исследуемой группой 1.- on the 5th day of observation - coefficient

characterize a certain violation of the ratio of the concentration of the final products of LPO and OAA of red blood cells. A comparative analysis of the calculated indices by biochemical parameters in the studied groups 1 and 2 can confirm the greater severity of the characteristics of the endogenous intoxication of biochemical monitoring in the studied group 2, compared with the studied group 1.

на 1 сутки после операции был выше в 1,6 раза с сохранением этой тенденции на 3 сутки наблюдений, коэффициент

на 3 сутки после операции был выше в 1,4 раза.Border changes in the intervals of the corresponding values of a number of parameters are shown during the transition from the reactive to the toxic stage of diffuse peritonitis, from the toxic stage to the lethal outcome of diffuse peritonitis (p <0.05). The toxic stage of diffuse peritonitis, in relation to the reactive stage, showed differences in changes in the biochemical parameters of free radical oxidation and antioxidant protection: on the 3rd day after surgery, 1.5 times higher OAA in blood plasma. In this case, the coefficient

by 1 day after surgery was 1.6 times higher with this trend remaining on the 3rd day of observation, the coefficient

3 days after the operation was 1.4 times higher.

The obtained data on calculated indices can serve as confirmation of the dynamics of biochemical tests of oxidative and antioxidant systems and indicate a greater severity of the imbalance in the activity of ceruloplasmin and plasma OAA, plasma OAA and red blood cell OAA in patients with diffuse toxic stage peritonitis than in patients with diffuse reactive stage peritonitis.

Patients with an unfavorable outcome of diffuse peritonitis, with respect to the toxic stage, also had the following distinctive features in biochemical tests of free radical oxidation and antioxidant protection, the level of MSM and their calculated indices:

был ниже в 1,6 раза с сохранением этой тенденции на 3 сутки наблюдений. На этом фоне коэффициент

на 1 сутки после операции был ниже в 2 раза, коэффициент

был ниже в 1,6 раза с сохранением этой тенденции до 5 суток наблюдений включительно.- On 1 day after surgery, a decrease in the level of OAA by 1.4 times, the coefficient

was 1.6 times lower with this trend remaining on the 3rd day of observation. Against this background, the coefficient

1 day after surgery was 2 times lower, the coefficient

was 1.6 times lower with this trend remaining up to 5 days of observations inclusive.

на 3 сутки после операции был выше в 1,6 раза с сохранением этой тенденции на 5 сутки наблюдений.- On the 3rd day after the operation, a decrease in MDA and OAA was noted by 1.7 and 1.5 times, respectively, on the 5th day after the operation, a decrease in the concentration of MDA was 2.1 times. In this case, the coefficient

3 days after the operation was 1.6 times higher with this trend remaining on the 5th day of observation.

The presence of a greater number of statistically significant differences in the dynamics of observations of the analyzed biochemical tests in patients with diffuse peritonitis with an unfavorable outcome of the disease, compared with patients with diffuse peritonitis of the toxic stage than in patients with diffuse peritonitis of the toxic stage, compared with patients with diffuse peritonitis of the reactive stage. The calculated indices revealed an imbalance of plasma OAA and plasma OAA and red blood cells, the concentration of MDA and plasma OAA, the level of MSM and the concentration of MDA.

Thus, in the group of patients with diffuse peritonitis, the most pronounced cascade of violations of the studied metabolic chains was manifested. In the early postoperative period, this examination group had characteristic changes during the transition from the reactive stage of diffuse peritonitis to the toxic stage, and also revealed a number of features in diffuse peritonitis with an unfavorable outcome of the disease, compared with a favorable outcome of the disease.

Monitoring of changes in hematological and clinical-biochemical parameters for assessing the condition of patients with abdominal pathology in the early postoperative period showed the manifesting nature of the dynamics of the calculated calculated indices of the indicators of oxidative and antioxidant systems in the blood and the level of molecules of average weight in the examined groups.

The dynamics of standard hematological and clinical-biochemical tests was analyzed:

- Hb hemoglobin concentration (hemoglobin cyanide method);

- level of hematocrit Ht (unified method of determination using a centrifuge);

- the number of blood cells (leukocyte blood count was calculated in% of the number of cells stained according to Gimzo-Romanovsky);

- the concentration of total protein (biuret method);

- total albumin concentration (OKA - bromocresol method),

urea level (reaction with diacetyl monooxime);

- bilirubin level (colorimetric diazomethod for determining total, bound (direct) and unbound (indirect) bilirubin).

The leukocyte intoxication indices (LII) were calculated according to Kalf-Kalif, Ostrovsky and Khimich and the nuclear shift index [27].

We studied the transport function of serum albumin (i.e., the binding ability of albumin, CCA), which was calculated according to the generally accepted formula as the ratio of the effective concentration of albumin (ECA) to the total concentration of albumin (OCA) multiplied by 100%. The determination of ECA was carried out in accordance with the procedure [34].

The ranges of the studied parameters and calculated indicators in the control group (54 practically healthy people without clinical manifestations of any diseases, mainly aged 20 to 44 years, outpatiently examined) were accepted as the norm (tables 1-4).

Then, abnormalities are calculated in the dynamics of observations in the groups (see table 4) of the survey with the derivation of a mathematical criterion characterizing the totality of the contributions of individual parameters to metabolic processes in the patient with abdominal pathology, including in emergency conditions, in the early postoperative period (1, 3, 5 days). The deviation from the norm is denoted by J and calculated by the formula:

,

,

where δ _n is the deviation of the n-dimension of the mathematical expectation of a quantity.

δ _{n is} calculated for each variation series in two positions:

1) the difference M-m is normal and M-m in the group examined during this observation period is the value corresponding to the minimum value of J;

2) the difference M + m is normal and M + m in the group examined during this observation period is the value corresponding to the maximum value of J.

Accordingly, criterion J is presented as a range of values for the blocks of the analyzed tests in the survey groups: hematological (J1) and clinical and biochemical (J2) indicators, biochemical parameters of free radical oxidation and antioxidant protection in the blood in comparison with the level of medium-weight molecules (J3), calculated indices of the ratios of the levels of the studied biochemical parameters (J4), the binding ability of albumin (J5) (tables 5-9). Then calculate the ranges of the total criterion J in the examined patients (table 10).

For predicting the outcome of diffuse peritonitis, the most significant ranges are J on days 1 and 3 of the postoperative period, which showed borderline changes depending on the stage and outcome of the disease. The values of the total criterion J with diffuse peritonitis on the 1st day after surgery in the range of 9937.56-14454.89, on the 3rd day - in the range of 8955.13-9350.07 indicate a risk of an unfavorable outcome of the disease. At the same time, on the 5th day of observation, the range of the total criterion J (10151.85-11816.29) in deceased patients overlapped with that in patients with diffuse terminal stage peritonitis (11445.87-12491.55). This may indicate that the 5th day of the postoperative period is a critical stage in the observation of patients with diffuse peritonitis of the terminal stage.

The obtained ranges of J can be used for comparative characteristics of the severity of endogenous intoxication of groups examined with abdominal pathology, for example, for retrospective analysis of a sample of patients for a certain period of examination.

The total criterion J for specific patients is calculated. For this, the data of clinical and biochemical examination of a particular patient for each of the parameters are compared with the ranges of this parameter in the control group (normal). Those. δ _n - the deviation of the n-measurement of the mathematical expectation of the patient’s magnitude is calculated as follows: the difference between the value of the indicator M in norm and the value of the parameter in the patient during this observation period is the value corresponding to the contribution to the total indicator J of each test.

Example. Patient K. in S.L., 54 years old, medical history No. 27730, was admitted to the intensive care unit and intensive care of hospital No. 6 of the city of Penza named after G.A. Zakharyin with a diagnosis of duodenal ulcer with perforation, diffuse toxic serous-fibrinous peritonitis.

The data of the clinical laboratory examination and calculation of criterion J are as follows. On the 1st day of observation, the hemoglobin concentration was 149 g / l, hematocrit 47%, red blood cells 4.43 million, stab neutrophils 35%, segmented neutrophils 52%, lymphocytes 10%, monocytes 3%, leukocyte intoxication index (LII) according to Kalf -Kalifu 12.08 conventional units, LII according to Ostrovsky 6.69 conventional units, LII according to Khimich 4.08 conventional units, nuclear shift index 0.67 conventional units, total concentration of albumin (OCA) 25 g / l On the 3rd day of the examination, the hemoglobin concentration was 128 g / l, the hematocrit level was 40%, the number of red blood cells was 4.09 million, stab neutrophils 20%, segmented neutrophils 67%, lymphocytes 10%, monocytes 3%, LII according to Kalf-Kalif 9.77 conventional units, LII according to Ostrovsky 6.69 conventional units, LII according to Khimich 5.02 conventional units, nuclear shift index 0.37 conventional units, OKA 32.4 g / l.

Against this background, plasma OAA on the 1st and 3rd day of the postoperative period reached 35.71% and 28.57%, respectively; Erythrocyte OAA 41.67% and 50%; the activity of ceruloplasmin 21.875 mg% and 23.625 mg%. The concentration of MDA in the blood was 1.45 μmol / L and 1.71 μmol / L. Blood plasma OA was 16.67% and 28.57%. The level of MSM reached 0.33 units. and 0.35 units respectively. The values of ECA were 11.47 and 8.41 g / l, SSA 45.88% and 25.96%.

The calculated indices had the following values on 1 day after the operation.

1. The calculated indices reflecting a possible imbalance in the activity of indicators of the antioxidant system.

был равен 2,73 и 1,79.Index 1:

was equal to 2.73 and 1.79.

был равен 3,41 и 2,53.Index 2:

was equal to 3.41 and 2.53.

2. The calculated indices reflecting a possible imbalance in the activity of indicators of oxidative and antioxidant systems.

был равен 0,52 и 1,1.Index 3:

was equal to 0.52 and 1.1.

был равен 1,38 и 1,96.Index 4:

was equal to 1.38 and 1.96.

был равен 0,21 и 0,3.Index 5:

was equal to 0.21 and 0.3.

0,56 и 0,54.Index 6:

0.56 and 0.54.

3. An index characterizing the ratio of the levels of molecules of medium weight and malondialdehyde.

был равен 4,22 и 3,86.Index 7:

was equal to 4.22 and 3.86.

The results of calculating the total criterion J in the patient on days 1 and 3 after the operation showed that its values fit into the corridors of the J values of the corresponding group of examined patients with diffuse peritonitis of the toxic stage:

The total criterion J y examined patient 5968.01 7311.56 The range of the total criterion J in the examined patients with diffuse toxic stage peritonitis 5928.72-6970.65 6809.76-7530.83

Using the proposed method, 219 patients with various surgical abdominal pathologies were examined.

The studied group 1 consisted of 53 patients with cholelithiasis with chronic cholecystitis, operated on laparoscopically in a planned manner, aged 24 to 65 years.

The studied group 2 included 46 patients with cholelithiasis with acute cholecystitis who did not have purulent-septic complications in the early postoperative period, aged 24 to 66 years.

120 patients with diffuse peritonitis from the age of 21 to 69 years were examined - study group 3. The group of patients with diffuse peritonitis included 30 people with a reactive stage of diffuse peritonitis, 60 people with a toxic stage of diffuse peritonitis, 10 people with a terminal stage of diffuse peritonitis, 20 a person with an unfavorable outcome of diffuse peritonitis.

All examined patients with diffuse peritonitis received generally accepted basic intensive care. With diffuse peritonitis of the toxic and terminal stages, it was supplemented according to indications with modern detoxification methods (indirect electrochemical blood treatment, ultraviolet irradiation of the blood), as well as local abdominal hypothermia according to the method of V.G. Vasilkova (Vasilkov VG Intensive therapy with the use of local hypothermia in emergency surgery of the abdominal cavity: Abstract. Thesis. Doct. Medical Sciences. - Sverdlovsk, 1977. - 34 p.). In 20.8% of cases, pancreatic necrosis was the cause of peritonitis; 42.5% and 17.5% of cases of diagnosing peritonitis occur in peritonitis due to perforated gastric and duodenal ulcers and damage to the hollow organs of the abdominal cavity, respectively; 8.3% was peritonitis of appendicular genesis; 6.7% - peritonitis due to acute cholecystitis, respectively; 4.2% - peritonitis due to acute intestinal obstruction.

According to the nature of the effusion in the abdominal cavity and the state of the gastrointestinal tract, 58.3% occur in diffuse serous-fibrinous peritonitis; 14.2% - for diffuse purulent peritonitis; 11.7% - for diffuse serous-fibrinous peritonitis; 8.3% for spilled enzymatic peritonitis; 5.0% - for diffuse hemorrhagic peritonitis; 2.5% - for diffuse hemorrhagic peritonitis.

To assess the severity of peritonitis, the Mannheim Peritoneal Index - MPI was used, providing for standard patient information (risk factors include patient age, gender, presence of organ failure, cancer, peritonitis lasting more than 24 hours, the colon as a source of peritonitis, diffuse peritonitis , the nature of the exudate: transparent, turbid putrid, fecal putrefactive). With an index of less than 20 points (first severity), mortality is 0%, from 20 to 30 points (second severity) 29%, more than 30 points (third severity) 100% [21].

Patients with diffuse peritonitis (study group 3) were characterized by the following MPI values:

1) with a favorable outcome of the disease:

- subgroup 1 - reactive stage - 7.9 ± 0.5 (1 severity),

- subgroup 2 - toxic stage - 14.8 ± 0.7 (43 patients - 1 severity and 17 patients - 2 severity);

- subgroup 3 - terminal stage - 22.5 ± 1.6 (3 patients - 1 severity, 6 patients - 2 severity, 1 patient - 3 severity);

2) with an unfavorable outcome of the disease (subgroup 3) - 25.6 ± 1.5 (4 patients - 1 severity, 10 patients - 2 severity, 6 patients - 3 severity).

Patients with diffuse peritonitis of the toxic stage, compared with the reactive stage, had 1.9 times higher values (p <0.05) of MPI. Patients with diffuse peritonitis of the terminal stage, compared with the toxic stage, had 1.5 times higher values (p <0.05) of MPI. In deceased patients with diffuse peritonitis, MPI values were close to the corresponding values in patients with diffuse peritonitis in terminal stage.

With diffuse peritonitis, a correlation of some components of criterion J and MPI values (p <0.05) were noted:

1) in the reactive stage - 3 days after surgery with J3 and J4 (r = 0.9);

2) in the toxic stage - 1 day after surgery with J2 and J4 (r = -0.33 and r = -0.49, respectively), 3 days after surgery with J1 (r = -0.41), by 5 day after surgery with J3 and J4 (r = -0.85 and r = -0.77);

3) at the terminal stage - on the 5th day after the operation with J1 (r = 0.35);

4) with an unfavorable outcome of the disease - 1 day after surgery with J1, J3 and J4 (r = 0.68, r = -0.73 and r = 0.57, respectively).

Thus, in emergency conditions in patients with diffuse peritonitis in the early postoperative period (1, 3, 5 days), a different degree of correlation between MPI values and criterion J calculated for individual blocks of the analyzed parameters was revealed. In the study groups, there was also a correlation between criterion J and LII. (Annex 1).

The control was the ranges of the analyzed tests in a group of 54 outpatient practically healthy people without clinical manifestations of any disease from the age of 20 to 44 years old, examined at the base of the blood transfusion department of Penza Hospital no. G.A. Zakharyin.

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Claims (2)

1. A method for assessing the severity of endogenous intoxication in emergency abdominal pathology in the early postoperative period, including blood sampling, clinical and biochemical studies of the parameters of antioxidant and oxidative systems in the blood against the background of standard hematological and clinical and biochemical tests, characterized in that the calculated indices I for identify the degree of balance of oxidative and antioxidant systems in the blood, determined by the following formula:

where is the value

then the mathematical criterion J is calculated, if it meets the values of the total criterion for certain diagnoses, identified by comparing with the previously calculated values in the examination groups, the severity of endogenous intoxication of the body corresponding to these nosologies is noted depending on the time of day after the operation, and the generalizing criterion for endogenous intoxication characteristic of diseases such as cholecystitis and / or complications such as diffuse peritonitis of the reactive stage is the presence of than 90% contribution to the minimum value and 90% contribution to the maximum value of the total criterion J values of the J at block biochemical parameters and on the albumin binding capacity, where there is a predominance of the contribution value of the total criterion J values J of the albumin binding capacity - up to 69%; a generalizing criterion for endogenous intoxication, characteristic of complications such as diffuse peritonitis of the toxic stage, is the presence of a significant contribution to the total criterion J according to the block of hematological and clinical and biochemical parameters; a generalizing criterion for endogenous intoxication, characteristic of complications such as spilled peritonitis of the terminal stage and / or spilled peritonitis with a fatal outcome, is the presence of up to 39.2% contribution to the total criterion J of a block of hematological parameters on the 5th day after surgery, and the calculation of criterion J, which of the analyzed tests, the totality of the contributions of individual parameters to the disruption of metabolic processes in the patient’s body, for the variation series, is performed in accordance with the formula:

where Δ _n is the deviation of the n-measurement of the mathematical expectation of the patient’s magnitude, corresponding to the contribution of each test to the total indicator J, and J is represented as a range of values - J _min -J _max, and Δ _{n is} calculated by the formulas for the variation series: for the minimum value parameter contribution to the total index J _min: Δ _n = (Mm normal) - (M-m in the group of patients); for the maximum value of the parameter contribution to the total indicator J _max : Δ _n = (M + m normal) - (M + m in the group of examined),

where M and m are variation statistics for small samples using Student t-test and are determined by the formulas: where δ is the standard deviation, determined by the formula:

Where

- the average value of I _i - a certain value of the sample. 2. A method for assessing the severity of endogenous intoxication with emergency abdominal pathology in the early postoperative period according to claim 1, characterized in that for calculating the total criterion J in a particular patient, the data of clinical and biochemical examination for each of the parameters are compared with the mathematical expectation or with the average value of this parameter in the control group.