RU2398518C1 - Method of diagnosing toxemia in case of malignant brain tumours - Google Patents

Abstract

FIELD: medicine. ^ SUBSTANCE: invention relates to field of medicine, namely to neurosurgery, neurotraumatology and clinical neurology. Before beginning and in dynamics of treatment clinical and laboratory parametres are determined. Each parametre is evaluated in points. Obtained points are summed up, degree of toxemia expressivity (Dt) is determined by formula: Dt=(P-c+P-l)/lim(P-c+P-l)ù100%, where P-c is sum of points of clinical parametres, P-l is sum of points of laboratory parametres. Obtained data with clinical and laboratory parametres are input into computer programme, carrying out computer monitoring in dynamics. ^ EFFECT: method allows to reduce time of diagnostics and increase its efficiency. ^ 4 tbl, 2 ex

Description

The invention relates to the field of medicine - neurosurgery and can be used for complex diagnostics with subsequent correction of toxemia syndrome and immunocomplex syndrome in the combined treatment of malignant brain tumors.

Toxemia is a poisoning of the blood by the toxins of bacteria that multiply in the infectious focus, as a result of which a person's body temperature rises, diarrhea and vomiting occur. With toxemia, there is the presence of endogenous intoxication in many infectious diseases and in the formation and decay of malignant brain tumors. Toxemic syndrome not only exacerbates the severity of the underlying disease, but also significantly complicates the implementation of intensive chemotherapy programs. It is known that any malignant neoplastic processes are accompanied by a cascade of pathological immuno-biochemical reactions leading to clinically manifest or latent development of tumor toxemia with an effect on all vital metabolic regulation systems. In malignant brain tumors, dysmetabolic disorders are inextricably linked to changes in the immune status and represent a single pathogenetic cycle, which significantly destabilizes homeostasis and adaptive reserves of the body. The causes of toxemia in malignant brain tumors are the violation of the blood-brain barrier, the cytotoxic effect of chemotherapy, the toxic and allergenic effects of drug therapy, autoimmune processes against the background of the progression of the main pathological process and surgical intervention. The degree of manifestation of toxemia is determined by the number of toxic biochemical metabolites in the blood and circulating immune complexes (CEC). Numerous methods for diagnosing toxemia are not sufficiently informative. When diagnosing toxemia, it is necessary to take into account the complexity and variety of pathogenetic mechanisms of its development in malignant brain tumors. Diagnostic and therapeutic measures should be comprehensive and included in the general treatment program of the underlying disease. At present, reliable clinical and laboratory criteria have not been identified that reflect the pathogenetic aspects of the development and progression of malignant brain tumors, as well as iatrogenic damage to the central nervous system during their combined treatment and the accompanying autoimmune processes and distametabolic reactions. There are no clear parallels between changes in the clinical picture and fluctuations in the immunobiochemical parameters of blood during the treatment of malignant tumors, which could be used not only to select the optimal therapeutic tactics, but also to predict possible complications. In addition, there is no unified diagnostic program for assessing toxemia at various stages of the combined treatment of malignant tumors; there is no working classification of it.

In medicine, a known method for the diagnosis of endogenous intoxication of patients with malignant tumors in the dynamics of treatment, see. “Efferent Therapy”, 2004, volume 10, No. 1, pp. 42-46, article of the authors: Smolyakova P.M., Zalutsky IV, Fradkin SF, Mavrichev SF "Endogenous intoxication of patients with generalized forms of malignant neoplasms in the dynamics of efferent therapy." According to the development mechanisms and clinical signs, tumor intoxication is one of the particular manifestations of endogenous intoxication. Endotoxemia is a consequence of real dysmetabolic manifestations that affect all vital systems and organs providing and regulating metabolism. An increase in the concentration of endogenous toxins, a decrease in the rate of anabolic reactions, an increase in the activity of proteolytic enzymes disrupt the physiological mechanisms of adaptation and compensation, develop toxic-dystrophic changes in the organs and life-support systems of the body, disrupt metabolic processes in cells and tissues, and damage the excretory and detoxification systems. In the dynamics of efferent therapy, the structural and functional state of erythrocyte membranes in patients with generalized forms of sarcomas, soft tissues, and nonorgan organ retroperitoneal malignancies was studied. In the process of diagnosing intoxication in patients, clinical parameters were determined, a large number of special laboratory tests were used: the concentration of urea, creatinine, molecules of medium molecular weight, and the paramets test. Fluorescence and electron-paramagnetic resonance spectroscopy were performed, which allows us to assess the severity and dynamics of endogenous intoxication syndrome by specific parameters, including blood elements. Therefore, the diagnosis was carried out using radiological, endoscopic and clinical methods.

The disadvantage of this method for the diagnosis of endogenous intoxication of patients with malignant neoplasms (tumors) in the dynamics of efferent therapy is that: this diagnosis is used in cancer patients with tumors of the retroperitoneal space; in the presence of a large number of parameters with their indicators, there is no classification for computer monitoring, which increases both the diagnostic time and the ability to track and compare indications during treatment; part of the specific diagnostic parameters is characteristic only for the diagnosis of toxemia in the case of oncological processes of the retroperitoneal space with malignant neoplasms, in particular the study of erythrocyte membranes. There is no diagnostic analysis after removal of malignant tumors. There is no comprehensive assessment of the parameters taking into account clinical and laboratory indicators of toxemia (endogenous intoxication), a diagnostic program and a working classification of toxemia in malignant tumors, an analysis of immunological studies and studies of neurological deviation.

The classification of toxemia syndrome in diseases of the blood system according to severity is indicated in the guidelines of the Research Institute of Hematology and Blood Transfusion, authors: prof. K.M. Abdulkadyrov, V. G. Scherbakova, A. A. Ganapiev, V. A. Shatrov, Yu. L. Katsadze, E. A. Ushakova “Hemocomponent therapy and infusion-detoxification therapy of blood system diseases”, Leningrad, 1985, pp. 10-11. In this method, a complex of clinical and laboratory criteria for toxemia in patients with diseases of the blood system is proposed, which allows to distinguish four degrees of severity of toxemia. Two criteria have been established: clinical and laboratory. Each criterion has its own parameters. The clinical criterion is divided into seven parameters: the patient’s condition, consciousness, complaints, skin, tongue, pulse, temperature. Each parameter is divided into four degrees of toxemia and has four (“quartile”) indicators. For example, the patient’s condition parameter has the following indicators: satisfactory - this is 1 severity of toxemia (mild), 2 degree - moderate severity; Grade 3 - severe severity; Grade 4 - an extremely severe degree of toxemia. Each parameter has its own indicators for four degrees of severity of toxemia: from the 1st degree - this is mild to 4th — extremely severe. The laboratory criterion has its own seven parameters: residual nitrogen, blood creatinine, total blood bilirubin, AlAt, AsAt, sublimate test, thymol test. Each parameter according to the severity of toxemia has its own indicators, also divided into four groups.

The disadvantages of the method for the diagnosis of toxemia in diseases of the blood system are: insufficient informativeness of the diagnostic indicators in the presence of malignant brain tumors, lack of diagnosis in the dynamics of treatment, which increases the treatment time and reduces the effectiveness of both the diagnosis of toxemia and its treatment. Lack of a comprehensive assessment of the degree of toxemia syndrome and endogenous intoxication. The lack of a working comprehensive classification with indicators of these syndromes during their development against the background of combined treatment for the removal of malignant brain tumors. Autoimmune processes are not taken into account in case of toxemia in the presence of malignant brain tumors, as well as features of the functioning of the blood-brain barrier of the central nervous system.

The closest solution is indicated in the article by the authors: Belozerova Yu.B., Mozhaev S.V., Ostreyko O.V. Petrov A.M. “Features of the immunological status of patients with malignant gliomas of the brain at different stages of treatment”, g. "Neurological Bulletin" 2007, t.39.1 s.90-93. Institute of the Human Brain N.P. Bekhtereva RAS. This study clarifies the dynamics of immunogram indices in patients with malignant gliomas at various stages of the development of the disease, estimates the effect of therapeutic measures on them, and establishes the characteristics of the immune status in patients with malignant gliomas in the period before and after the operation period. Verification of the diagnosis was carried out taking into account the analysis of data from a comprehensive examination using the results of magnetic resonance imaging (MRI) and positron emission tomography (PET) with C-methionine. Assessment of the state of the immune system included determination of quantitative and functional indicators in peripheral blood: subpopulations of lymphoid cells, ratio of CD4 + / CD8 + cells - immunoregulatory index, immunoglobulins of classes A, G, M, sensitivity of immunocytes in the presence of neurospecific antigens. Immunological studies were performed before surgery and in the period 5-7 days after.

The disadvantages of this solution are: the lack of a comprehensive assessment of laboratory indicators of toxemia in malignant brain gliomas, the lack of clinical criteria in conjunction with laboratory criteria, the lack of a working classification of toxemia in malignant brain tumors, and the diagnostic program, respectively, and the lack of the possibility of using computer monitoring, which allows you to reduce the time of diagnosis and research and increase the effectiveness of diagnosis and treatment.

The technical result of the proposed solution to the method of diagnosing toxemia in malignant brain tumors is to increase the information content of toxemia syndromes in the presence of malignant brain tumors by increasing the quantitative and qualitative diagnostic parameters in the dynamics of treatment at its various stages, leading to an increase in the effectiveness of complex diagnostics that allow to perform after removal of malignant brain tumors increase treatment efficacy, in enshit treatment time and receiving potent cytostatic and hormonal drugs, to classify indicators of clinical and laboratory criteria, implement a computer monitor, which allows to reduce diagnosis time and enhance its efficiency.

This result is achieved by the fact that in the method for the diagnosis of toxemia in malignant brain tumors, including the evaluation of clinical and laboratory research methods, studies are carried out at the beginning and in the dynamics of treatment and the obtained indicators are evaluated in points, in clinical indicators - condition: satisfactory - 0, average severity - 1, severe - 2, extremely severe - 3 points; consciousness: clear - 0, stunning - 1, psychomotor agitation - 2, lack of consciousness - 3; reaction to external stimuli: distinct - 0, delayed - 1, lack of an adequate reaction - 2; total score of complaints: weakness - 0, appetite - 1, nausea - 2, vomiting - 3, headache - 5; mucous membranes: wet - 0, dry - 1, dry with a plaque - 2; skin: wet - 0, dry - 1, dry icteric - 2; pulse, bpm: less than 80 - 0, 80-99 - 1, 100-119 - 2, more than 120 - 3; breathing in minutes: less than 20 - 0, 20-22 - 1, 23-24 - 2, more than 24 - 3; temperature, ° С: less than 36.9 - 0, 36.9-37.4 - 1, 37.5-38.0 - 2, more than 38 - 3; laboratory indicators - urea in mol / l: less than 7.5 - 0, 7.5 - 1, 7.6-8.0 - 2, more than 8.0 - 3; total bilirubin in µmol / l: less than 26 - 0, 26-35 - 1, 36-50 - 2, more than 50 - 3; ALT in E / L: less than 50 - 0, 50-62 - 1, 63-74 - 2, more than 74 - 3; ACT in E / L: less than 38 - 0, 38-58 - 1, 59-72 - 2, more than 72 - 3; creatinine in mol / L: less than 0.12 - 0, 0.121-0.144 - 1, 0.145-0.161 - 2, more than 0.161 - 3; ESR in mm / h: less than 16 - 0, 16-20 - 1, 21-30 - 2, more than 30 - 3; LII: less than 1.23 - 0, 1.23-1.30 - 1, 1.31-1.40 - 2, more than 1.40 - 3; CEC in units optical density: less than 0,081 - 0, 0,081-0,09 - 1, 0,091-0,120 - 2, more than 0,120 - 3; oligopeptides, plasma in g / l: less than 0.49 - 0, 0.49-0.54 - 1, 0.55-0.65 - 2, more than 0.65 - 3; oligopeptides, red blood cells in g / l: for women it is equal to or less than 0.47, for men it is equal to or less than 0.49 - 0, for women more than 0.47, for men more than 0.49 - 3; oligopeptides, urine in g / l: for women less than or equal to 5.18, for men less than or equal to 5.38 - 0, for women more than 5.18, for men more than 5.38 - 3 points, while the obtained points summarize , determine the severity of toxemia (St) by the formula St = (∑B-k + ∑B-l) / lim (∑B-k + ∑B-l) × 100%, where ∑B-k - the sum of the points of clinical indicators , ∑Б-л - the total score of laboratory parameters, and with clinical and laboratory parameters are entered into a computer program, performing computer monitoring in the dynamics of treatment.

The invention is expressed in the aggregate of essential features sufficient to achieve the technical result provided by the invention.

Toxemia is the presence in the blood of toxins of endo- (or exogenous) origin in non-physiological concentrations that cause toxicosis, a pathological syndrome accompanied by morphological and functional changes at the level of organs and systems of the body.

Intoxication is a clinical manifestation of a pathological condition that occurs as a result of the action on the body of toxins of endogenous and exogenous origin, which is the metabolic response of the body to any aggressive factor.

Guided by traditional approaches, the diagnosis of toxemia in malignant brain tumors is evaluated by clinical and laboratory research methods. The selection of clinical and laboratory indicators of toxemia is carried out on the basis of the principle of maintaining maximum "discriminatory properties" of the selected criteria. To record the manifestations of toxemia at the clinical level, evaluate: complaints and the general clinical status of patients (severity of the condition, skin and mucous membranes, heart rate and respiration, body temperature); cerebral symptoms as a manifestation of hypertension syndrome (headaches, nausea and vomiting, level of consciousness and speech production, reaction to external stimuli). To assess laboratory indicators of toxemia, the following indicators are used: total bilirubin, urea, creatinine, activity of alanine aminotransferases - ALT and aspartate aminotransferases - ACT, leukocyte intoxication index - LII, plasma oligopeptides, blood and urine erythrocytes, and erythrocyte sedimentation rate -. Verification of autoimmune processes includes the determination of circulating immune complexes (CICs). In view of the possible deviation of normative laboratory parameters, endemic factors, various units of expression of quantitative values, they are guided by standard standards of biochemical and immunological indicators.

A method for diagnosing toxemia in malignant brain tumors involves the determination of clinical and laboratory criteria. Their parameters and indicators with an assessment in points depending on the patient's condition are classified and summarized in tables 1 and 2.

Table 1 Clinical criteria Options Indicators Points condition Satisfactory 0 Moderate one Heavy 2 Extremely heavy 3 Consciousness Clear 0 Stun one Anxiety, 2 Psychomotor excitation Lack of consciousness 3 Reaction to external stimuli Distinct 0 Slow motion one Lack of adequate reactions 2 Total score of complaints Weakness 0 Appetite one Nausea 2 Vomiting 3 Headache 5 Mucous membranes Wet 0 Dry one Dry with a touch 2 Skin integument Wet 0 Dry one Dry icteric 2 Pulse, beats.min Less than 80 0 80-99 one 100-119 2 More than 120 3 Breath min Less than 20 0 20-22 one 23-24 2 More than 24 3 Temperature ° C Less than 36.9 0 36.9-37.4 one 37.5-38.0 2 More than 38 3

The maximum number of points of clinical criteria 26.

Since intracranial hypertension is caused by the presence of a tumor, cerebral edema, cerebrospinal fluid circulation, the clinical criterion is evaluated taking into account the presence of malignant brain tumors, intracranial hypertension and focal neurological deviation, therefore, the “Stun” parameter and the “Respiration” parameter are entered into its “Consciousness” parameter with its “Respiration” indicators.

Stunning is a form of clouding of consciousness, characterized by an increase in the threshold of all external stimuli, deceleration, difficulty in the flow of mental processes, scarcity of ideas, incompleteness or lack of orientation in the environment.

table 2 Laboratory criterion Options Indicators Points Urea, mol / L Less than 7.5 0 7.5 one 7.6-8.0 2 More than 8.0 3 Total bilirubin, µmol / l Less than 26 0 26-35 one 36-50 2 More than 50 3 ALT, E / L, Alanine Aminotransferase Less than 50 0 50-62 one 63-74 2 Over 74 3 ACT, E / L, aspartate aminotransferase Less than 38 0 38-58 one 59-72 2 More than 72 3 Creatinine, mol / L Less than 0.12 0 0.121-0.144 one 0.145-0.161 2 More than 0.161 3 ESR, mm / h, erythrocyte sedimentation rate Less than 16 0 16-20 one 21-30 2 Over 30 3 LII, leukocyte intoxication index Less than 1.23 0 1.23-1.30 one 1.31-1.40 2 More than 1,40 3

CEC, units optical density circulating immune complex Less than 0,081 0 0,081-0,09 one 0,091-0,120 2 More than 0.120 3 Oligopeptides, plasma, g / l Less than 0.49 0 0.49-0.54 one 0.55-0.65 2 More than 0.65 3 Oligopeptides, red blood cells, g / l G. less than or equal to 0.47; M. less than or equal to 0.49, 0 J. more than 0.47, M. more than 0.49 3 Oligopeptides, urine, g / l W less than or equal to 5.18; M. less than or equal to 5.38, 0 J. more than 5.18, M. more than 5.38 3

The maximum number of laboratory score points is 34.

The maximum number of indicators of clinical and laboratory criteria, i.e. the limit, lim, is 60.

Verification of autoimmune processes includes the determination of circulating immune complexes in peripheral blood, taking into account the presence of malignant brain tumors with studies of intracranial hypertension and focal neurological deviation, because hypertension in the cranial cavity is caused by the presence of a pathological formation in it, cerebral edema, hypersecretion or insufficiency of cerebrospinal fluid outflow (CSF).

All parameters of the clinical and laboratory criteria with their indicators are entered into the database of the computer program, setting each indicator with its own score depending on the patient's condition - its severity of toxemia damage. When diagnosing a patient, the parameters of the clinical and laboratory criteria are determined, indicators and corresponding scores are summarized. In the process of computer monitoring, the severity of toxemia is determined by the formula.

With _t = (∑B-k + ∑B-l) / lim (∑B-k + B-l) × 100%,

where St is the severity of toxemia,%;

∑Б-к - the total score of clinical indicators. According to the indications in table 1, the maximum score is 26;

∑B-l - the total score of laboratory indicators. According to table 2, the maximum (or marginal) total score of the laboratory criterion is 34.

The proposed method uses a classification of 4 degrees of severity of toxemia. The total number of points is 60, therefore from 0 to 15 is 1 degree of severity, 16-30 is 2 degree of severity, 31-45 is 3 degree of severity, 46-60 is 4 degree. These percentages correspond to: 1 degree - from 0 to 25; 2 degree - 26-50; 3 degree - 51-75; Grade 4 - 76-100% (table 3).

Table 3 0-15 points 16-30 points 31-45 points 46-60 points 0-25% 26-50% 51-75% 76-100% 1 degree of toxemia 2 degree of toxemia 3 degree of toxemia 4 degree of toxemia

Thus, the obtained comprehensive scoring of criteria with parameters and their indicators allows us to determine the severity of toxemia both before treatment and in the dynamics of treatment according to the proposed mathematical formula. In this case, it is possible to fix, evaluate and monitor the diagnosis in its dynamics during treatment and the patient's condition before and after removal of malignant brain tumors.

A method for the diagnosis of toxemia at the stages of the combined treatment of malignant brain tumors was developed at the Institute of Human Brain named after NP Bekhtereva of the Russian Academy of Sciences and passed clinical trials in 47 patients with malignant brain tumors. The age of patients ranged from 21 to 73 years. All patients were examined in the neurosurgical department of the clinic of the institute. The most common complaints at admission were headaches without a clear localization, general weakness and dizziness of a non-systemic nature, loss of appetite, nausea, vomiting, impaired vision in the form of amblyopia, weakness in the contralateral tumor of the extremities, episindrome (as partial somatomotor or somato -sensory attacks, sometimes with secondary generalization, less often - primary generalized). Most patients (76%) were admitted to the clinic of the institute with a clear mind or in the degree of moderate stunning (9.5%). The most common neurological status was central paresis of facial muscles, cortical ataxia, oculomotor disorders, aphatic disorders, contralateral tumor focus pyramidal insufficiency and / or hemihypesthesia, and irritative syndrome. Moreover, in 19% of patients focal prevailed, and in 45% - cerebral symptoms.

All patients underwent osteoplastic craniotomy with the most radical (not less than 75% of the tumor tissue volume) removal of malignant brain tumors with subsequent verification of the histological structure of the tumor (table 4).

Table 4 The histological structure of the tumor Number of patients Glioblastoma 21 Anaplastic astrocytoma 21 Anaplastic oligodendroglioma one Brain metastasis four

Surgical treatment was carried out in conditions of multicomponent anesthesia with complete muscle relaxation and mechanical ventilation, as well as clinical and physiological monitoring of the condition of patients during and after surgery. Based on data on the histiostructure of the removed tumor tissue in the subsequent period, adjuvant (chemoradiation) therapy was performed. All patients underwent clinical and laboratory computer monitoring of the manifestations of toxemia and immunocomplex syndrome both before the operation and on the 5th, 10th, and 14th days of the postoperative period.

To record the manifestations of toxemia at the clinical and subclinical levels during the examination of patients, the following were evaluated: complaints and general clinical status, general condition, skin and mucous membranes, heart rate and respiration, body temperature, manifestations of hypertension syndrome, cerebral symptoms (headaches, nausea and vomiting , level of consciousness and speech production, reaction to external stimuli). The dynamics of the following parameters was also determined: blood parameters - total bilirubin, transaminase level, creatinine, ESR, LII, blood immunological data, as well as the level of circulating immune complexes (CEC). For a reliable assessment of the manifestations of toxemia, the level of oligopeptides was determined (in blood plasma, on red blood cells, and in urine). All data of parameter indicators are entered into the database of a computer program and the severity of toxemia is determined.

Before surgery to remove malignant brain tumors

The degree of toxemia The number of patients, N one one 2 36 3 9 four one 5th day after surgery one 3 2 17 3 25 four 2

Based on the calculations according to the proposed diagnostic program, in the preoperative period, 2 degree of toxemia lesion prevailed (26-50%), and in the postoperative period, 3 degree (51-75%). On the 5th day of the postoperative period, patients underwent correction of toxemia using the methods of infusion-detoxification therapy and plasmapheresis. On the 10th day after the correction, 1 degree of toxemia lesion prevailed (0-25%).

The degree of toxemia The number of patients, N one 40 2 6 3 one four 0

These data demonstrate the effectiveness of the adequate use of toxemia correction methods based on timely and high-quality diagnosis and classification of these syndromes.

Clinical example No. 1. Patient G., 51, was admitted to the hospital with complaints of sharp diffuse headaches, general weakness, loss of appetite, nausea, memory loss. On admission, the patient’s condition is of moderate severity, mucous membranes and skin are dry and icteric, pulse is up to 70 beats per minute, pressure 140/100 mm Hg, low-grade fever 37-37.1 ° С, tachypic breathing up to 20 min Manifestation of the disease in 2001 by a single primary convulsive epipriceps.

In the neurological status, the patient is conscious, correctly oriented in place and time, is somewhat inhibited, lethargic and apathetic, there is no aphatic disorder, however, it is laconic, full movement of the eyeballs, no anisocoria, left-side power and reflex hemiparesis, abdominal reflexes are languid with an emphasis on the right, coordination seems intact, there is no loss of sensitivity, there are signs of Oppenheim from the left foot. There is no stagnation at the fundus, and full left-sided hemianopsia in the fields of vision. With EEG: the presence of slow pathological and epileptiform activity in the leads from the right hemisphere of the brain, dysfunction of the median stem structures, indirect signs of intracranial hypertension. In ultrasound dopplerography, a pattern of obstructed cerebral perfusion, more pronounced on the right (to the midbrain artery), pronounced venous dyshemia, mainly in the basal, orbital and jugular collectors, is more on the right. With echoencephalography - the dislocation of the median structures is 7.5 mm from right to left along the middle path, lateral echocomplexes on the right are recorded. Magnetic resonance imaging of a brain study with contrast revealed a volumetric process of the right temporal lobe with a zone of perifocal edema in the projection of the temporal and posterior parts of the frontal lobe of the brain. In laboratory studies, an increase in ALT activity (up to 50 U / L), plasma oligopeptides - up to 0.56 g / l and erythrocytes - up to 0.81 g / d. A positive reaction C - reactive protein (CRP) was noted. According to the proposed classification, the severity of toxemia was 48% - the 2nd degree of toxemia. Due to the rapid deterioration of the patient's condition in the form of an increase in cerebral and focal neurological symptoms, the appearance of hemodynamic instability, and a tendency to bradycardia, the patient was operated on the second day after admission for emergency reasons. Under endotracheal anesthesia, osteoplastic trepanation was performed in the right frontotoparietal-temporal region, subtotal tumor removal (according to histology, anaplastic astrocytoma) of the right temporal lobe of the brain.

By the 5th day of the postoperative period, the patient's condition is severe, tachycardia up to 96 beats. per minute, blood pressure - 160/100 mm Hg, spontaneous rhythmic breathing (tachypical up to 24 per minute), hyperthermia up to 38.8 ° C, dry and icteric skin, mucous membranes - dry with a touch. The level of consciousness is stunning, it is accessible to persistent verbal contact, however, monosyllabic intermittent speech, marked negativity in behavior and lack of criticism of one’s state, frequent episodes of psychomotor agitation. When an ophthalmological examination on the fundus there are congestive disks of the optic nerves. Based on a detailed clinical and neurological examination of the patient, including MRI and PET studies, hemorrhage in the operative area was excluded. The patient was given active etiopathogenetic and symptomatic therapy, including sedatives and anticolvantsants. In studies by laboratory criteria, an increase in ALT was noted - 448.6 U / L and ACT - 271.0 U / L, creatinine 0.122 mol / L, urea - 11.6 mmol / L, total bilirubin - 24.2 mmol / L, plasma oligopeptides - 0.062 g / l, red blood cells - 0.91 g / l and urine - 5.41 g / l, leukocyte intoxication index - 1.7, ESR - 34 mm / h, positive CRP reaction. An immunological examination: an increase in the CEC - 0.01 opt. units density. In cerebrospinal fluid analyzes: cytosis within 15/3, protein 0.63 g / l. In this case, clinical and laboratory changes with total indicators according to the analytical formula were interpreted as a manifestation of toxemia with a 3rd (71%) degree of severity. The etiopathogenesis of these syndromes was explained by the nature of the tumor process, the severity of surgery (surgical trauma, violation of the blood-brain barrier), post-transfusion reactions of a non-homolytic type (after using donor hemocomponents), and the possible individual intolerance to high doses of the drugs used (sedatives, anticonvulsants) postoperative period. The patient underwent a complex of infusion-detoxification therapy in combination with 5 sessions of plasmapheresis. After this, the patient's condition improved. By the 10th day of the postoperative period, the patient in a compensated state, clear consciousness, is contactable and adequate, notes satisfactory subjective well-being, there is a clear regression of cerebral symptoms, focal neurological symptoms do not increase During an ophthalmological examination on the fundus, a clear regression of the optic nerves. Clinical biochemical and immunological parameters of urine and blood were normalized. Diagnosis of toxemia according to computer monitoring corresponded to severity 1 (22%). On the 10th day after the operation, the patient started chemotherapy treatment.

Clinical example No. 2. Patient S., 27 years old, was admitted to the hospital with complaints of intense diffuse headaches, general weakness, loss of appetite, nausea and vomiting. Upon admission, the patient's condition is severe, mucous membranes and skin are dry, pulse up to 62 beats. per minute, blood pressure - 115/70 mmHg, temperature - 37.3 ° C, respiratory rate - up to 20 per minute. The manifestation of the disease 4 months before admission to the clinic. In neurological status: consciousness is narrowed to stunning, speech is monosyllabic, intermittent, moderate restriction of gaze up, there is no anisocoria, there is reflex and power pyramidal insufficiency on the left, abdominal reflexes on the verge of absence, sensitivity is preserved, bilateral pathological stop signs. Severe edema of the optic disc. With EEG: marked pathological activity in the leads from the right hemisphere of the brain, severe dysfunction of the stem structures, signs of intracranial hypertension. Ultrasound dopplerography shows a marked decrease in cerebral perfusion, mainly in the pool of the right midbrain artery, venous dyshemia in the basal, orbital and jugular collectors, more on the right. With echoencephalography, the dislocation of the middle structures from right to left is up to 8 mm. An MRI study of the brain with contrast enhancement revealed a volumetric process of the right temporal lobe with a perifocal zone in the projection of the right frontal and temporal lobe of the brain. In studies according to laboratory criteria, indicators of ALT activity were noted - 45.0 U / L, ACT - 42.0 U / L, creatinine - 0.106 mol / L, leukocyte intoxication index - 1.6, plasma oligopeptides - 0.51 g / L urine - 5.33 g / l. An immunological study showed a moderate increase in the CEC to 0.087 optical. units density. According to computer monitoring by the analytical formula, the severity of toxemia was 2 degree (44%).

In connection with the worsening condition in the form of an increase in cerebral and focal neurological symptoms, the patient was operated on according to emergency indications. Under endotracheal anesthesia, osteoplastic trepanation was performed in the right frontotoparietal-temporal region, subtotal tumor removal (according to histological examination - metastatic adenocarcinoma) of the right temporal lobe of the brain. By the 5th day of the postoperative period, the patient's condition is severe, spontaneous rhythmic breathing (up to 22 per min), hyperthermia - up to 38.8 ° C, dry mucous membranes and skin. Level of consciousness - stunning, elements of psychomotor agitation. With an ophthalmological study, pronounced phenomena of stagnation of the optic nerve discs. Studies using laboratory criteria showed an increase in ALT activity - 65.0 U / L, ACT - 47.0 U / L, plasma oligopeptides - 0.88 g / L, LII - 1.9, ESR - 48 mm / h. An immunological examination: CEC - 0.117 opt. units density. In cerebrospinal fluid analyzes: cytosis within 5/3, protein - 0.63 g / l. In this case, clinical and laboratory changes were interpreted as manifestations of toxemia with 3-4 (76%) severity in the early postoperative period. The patient was given a course of infusion-detoxification therapy in combination with 5 sessions of plasmapheresis. After the treatment, the patient's condition improved: by the 10th day of the postoperative period, the patient is in a compensated state, clear consciousness, contact and adequate, notes a satisfactory subjective state of health. In addition, there is a regression of cerebral symptoms, focal neurological symptoms without buildup. With an ophthalmic examination, the fundus and visual fields are normal. Clinical, biochemical and immunological parameters of blood and urine are normal. Registered 1 degree of toxemia (23%).

So, it should be noted that timely diagnosis and its adequate correction for toxemia allowed to effectively stop its expressed manifestations and accelerate the start of adjuvant therapy.

The use of the invention increases the efficiency of diagnosis, the information content of toxemia syndromes in the presence of malignant brain tumors, allows us to evaluate the pathogenetic community of dysmetabolic and autoimmune processes against the background of changes in the permeability of the blood-brain barrier in the process of complex treatment of toxemia when removing malignant brain tumors. Diagnostic efficiency was enhanced by an increase in quantitative and qualitative parameters with their diagnostic indicators, such as leukocyte intoxication index, oligopeptides, circulating immune complexes in combination with many indicators of clinical and laboratory criteria. Clinical and laboratory manifestations of toxemia are evaluated in the dynamics of treatment: the preoperative period and on the 5th, 10th, 14th day of the postoperative periods, as a result of which current correction of toxemia therapy is carried out. Systematization and optimization of a comprehensive diagnosis and classification of toxemia with its parameters and indicators was carried out with the creation of a computer program that allows computer monitoring in the entire treatment process to determine the severity of the patient's toxemia, which ultimately improves efficiency and reduces treatment time. The proposed method for the diagnosis of toxemia in malignant brain tumors was tested in 47 people at the clinic of the Institute of the Human Brain of the Russian Academy of Sciences, showed effective and positive results and can be proposed in neurosurgical practice.

Claims (1)

A method for the diagnosis of toxemia in malignant brain tumors, including the assessment of indicators of clinical and laboratory research methods, characterized in that the studies are carried out before and in the dynamics of treatment, the obtained indicators are evaluated in points, clinical indicators - condition: satisfactory - 0, moderate - 1 , severe - 2, extremely difficult - 3 points; consciousness: clear - 0, stunning - 1, psychomotor agitation - 2, lack of consciousness - 3; reaction to external stimuli: distinct - 0, delayed - 1, lack of an adequate reaction - 2; total score of complaints: weakness - 0, appetite - 1, nausea - 2, vomiting - 3, headache - 5; mucous membranes: wet - 0, dry - 1, dry with a plaque - 2; skin: wet - 0, dry icteric - 2; pulse, beats.min: less than 80 - 0, 80-90 - 1, 100-119 - 2, more than 120 - 3; breathing in minutes: less than 20 - 0, 20-22 - 1, 23-24 - 2, more than 24 - 3; temperature, ° С: less than 36.9 - 0, 36.9-37.4 - 1, 37.5-38.0 - 2, more than 38 - 3; laboratory indicators - urea, mol / l: less than 7.5 - 0, 7.5-1, 7.6-8.0-2, more than 8.0 - 3; total bilirubin, mmol / l: less than 26 - 0, 26-35 - 1, 36-50 - 2, more than 50 - 3; ALT, E / L: less than 50 - 0, 50-62 - 1, 63-74 - 2, more than 74 - 3; AST, E / L: less than 38 - 0, 38-58 - 1, 59-72 - 2, more than 72 - 3; creatinine, mol / L: less than 0.12 - 0, 0.121-0.144 - 1, 0.145-0.161 - 2, more than 0.161 - 3; ESR, mm / h: less than 16 - 0, 16-20 - 1, 21-30 - 2, more than 30 - 3; LII: less than 1.23 - 0, 1.23-1.30 - 1, 1.31-1.40 - 2, more than 1.40 - 3; CEC in the unit of optical density: less than 0,081 - 0, 0,081-0,09 - 1, 0,091-0,120 - 2, more than 0,120 - 3; oligopeptides, plasma, g / l: less than 0.49-0, 0.49-0.54-1, 0.55-0.65-2, more than 0.65-3; oligopeptides, red blood cells, g / l: for women it is equal to or less than 0.47, for men it is equal to or less than 0.49 - 0, for women more than 0.47, for men more than 0.49 - 3; oligopeptides, urine, g / l: for women less than or equal to 5.18, for men less than or equal to 5.38 - 0, for women more than 5.18, for men more than 5.38 - 3 points; at the same time, the obtained points are summarized, the severity of toxemia (St) is determined by the formula: St- (∑B-k + ∑B-l) / lim (∑B-k + ∑B-l) × 100%, where ∑B- k - the total score of clinical indicators, ∑B-l - the total score of laboratory parameters and with clinical and laboratory parameters are entered into a computer program, performing computer monitoring in the dynamics of treatment.