RU2426992C1 - Method for prediction of clinical course of cerebral wound dystrophy - Google Patents

Abstract

FIELD: medicine.

SUBSTANCE: for the first hour following admission of a patient with a severe craniocerebral injury (CCI) to hospital, human recombinant erythropoietin (Epocrin) 10000 IU is introduced intravenously. Prior to the introduction of erythropoietin and 24 hours thereon, the blood serum cytokine concentration is evaluated: IL-6, IL-10; red blood cells are analysed for the concentration of malonic dialdehyde (MDA) and superoxide dismutase (SOD). Thereafter, for each of the derived values, its percentage change after the introduction of erythropoietin is determined by calculating the relation of a difference of each of the derived values prior to the introduction of erythropoietin to a related value prior to the introduction of erythropoietin. If the IL-6 concentration is increased by 35 % and more, the IL-10 concentration by 20 % and lower, the red blood cell MDA concentration - by 30 % and more, the SOD concentration by 45 % and less, an unfavourable course of cerebral wound dystrophy is predicted.

EFFECT: use of the method enables high-precise prediction of the cerebral wound dystrophy outcome within the least invasive research, and selection or correction of the conducted intensive care.

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Description

The invention relates to medicine, namely to neuroresuscitation, neurosurgery (neurotraumatology), and can be used to predict the course of traumatic brain disease (TBHM) in patients with severe traumatic brain injury (TBI), both isolated and combined.

Brain injuries and their consequences remain one of the most difficult and unresolved problems of modern medicine and are of great importance in connection with their prevalence and severe medical and social consequences (Likhterman L.B. et al., 1993; Konovalov A.N. et al. ., 1999; Gamer, 2000; Nepomnyaschy et al., 2001; Badikian et al., 2005).

Among all injuries, head injury (TBI) is the leading cause of death (A. Romodanov et al., 1992; Maas et al., 2000). Every year, 1.5 million people die from traumatic brain injury (TBI) in the world, and 2.4 million become disabled. In Russia, about 600 thousand people receive TBI every year, 50 thousand of them die, and another 50 thousand become disabled. Affected are, as a rule, persons of a young, able-bodied age. In terms of the number of survivors due to premature death, head injury and other injuries account for almost half of the loss of Russia's labor potential, exceeding those from diseases of the cardiovascular system by 4.5 times (Likhterman L., 2000). All of the above determines the relevance of further research on the pathogenesis of TBI in order to improve the treatment of this disease.

If the lesion focus is localized in the brain, then it is customary to talk about traumatic brain disease (TBHM), and its characteristic is associated with a decrease or elimination of the central nervous system role, coordinating with respect to the functioning of organs and systems (Belitskaya TS, 2000; Belyaevsky A. D. et al. 2001, 2003).

Conducted research on the medical-scientific and patent literature revealed various ways to determine the dynamics of the head injury and predict the course of TBHM.

So, in an article by Alimov R.A., Frolov V.I., Dosmukhamedov Kh.K. Assessment of the condition of patients with combined traumatic brain injury // Honey. Journal of Uzbekistan, 1990, No. 3, pp. 30-32, describes a method for assessing the condition of patients with head injury, based on assessing the condition of the victim by the rate of reaction of the body - the ratio of the number of neutrophilic leukocytes to lymphocytes (neutrophilic-leukocyte index - NLI) in the patient’s blood . However, despite its simplicity, this method requires a significant investment of time, since it involves daily dynamic monitoring of NLI, an objective assessment of treatment results and its correction.

In the article Krylova V.E., Lazareva L.V., Zyangirova S.T. Predicting the dynamics of the course of traumatic brain injury // Kazan Medical Journal, 1992, vol. 73, No. 2, pp. 93-96, a method for predicting the dynamics of the course and outcome of brain injury by changing the activity of cholinesterase in the arterial (common carotid artery) and venous (in the jugular vein) blood. This method is based on determining the deviation of cholinesterase activity in arteriovenous difference in the blood flowing in and out of the brain and calculating the severity index of TBI in normal and pathological conditions. However, this method is quite traumatic, time-consuming and also requires significant time costs.

In the work Korolyuk M.A., Ivanova L.I., Mayrova I.G., Tokareva V.E. Method for determination of catalase activity // Lab. Case, 1988, No. 1, pp. 16-19, describes a method for predicting a brain injury by examining the activity of catalase in the cerebrospinal fluid of victims.

Also known is the patent of the Russian Federation No. 2146060 (published in BI No. 6, 2000) "A method for determining the severity of a head injury", which involves examining the cerebrospinal fluid of the victim and determining the concentration of lipid peroxidation products in it - malondialdehyde and diene conjugates.

The disadvantage of these methods is the trauma, which is associated with the collection of cerebrospinal fluid from the victim. The study is conducted 0.5-3 hours after the injury, which allows only at the time of the examination to determine the severity of the patient's condition, but not to predict the further course of the disease. To make a forecast using this method, it is necessary to determine the indicators within 3-14 days, which is a laborious process that requires a significant amount of blood from a patient who needs this blood.

Known patent No. 2178179 (Published: January 10, 2002) "A method for predicting the course of traumatic brain disease (TBHM)", which involves the study of a biological fluid with the determination of the concentration of malondialdehyde - MDA in it, characterized in that the victim is produced on the second day after the injury venous blood sampling, in which, in addition to determining the MDA value, the values of other indicators of lipid peroxidation (POL) are determined: total peroxidase activity - SPA and content of Schiff bases - SHO, p after blood sampling, the patient is injected intravenously with 20 mg of epithalamin diluted in 10 ml of isotonic NaCl solution, 6-8 hours after the administration of epithalamine, venous blood is taken again from the patient, in which MDA, SPA and SHO values are again determined, and when the values are reduced FLOOR: MDA and SPA - less than 30% of each, SHO - less than 15% predict an unfavorable course of TBHM.

The disadvantages of this method include the fact that only the dynamics of the metabolic metabolic recovery process is assessed by the level of lipid peroxidation markers, while the claimed method examines the dynamics of the humoral response (cytokines), coupled with biochemical markers of oxidative stress (MDA) and an antioxidant component protection (superoxide dismutase) in response to the introduction of epocrine.

Known patent No. 2183834 (Published: 06/20/2002) "A method for predicting the outcome of the treatment of traumatic brain injury:" the patient is examined for cerebrospinal fluid, and in the first 5-7 days after the injury, the number of neutrophils, the level of urea, the activity of lactate dehydrogenase are determined in it ( LDH), alkaline phosphatase (ALP) and, if the number of neutrophils is more than 10 in 1 mm ³ , the level of urea is higher than 10 mmol / L, LDH activity is higher than 30 IU / L, ALP is higher than 5 IU / L, an unfavorable outcome of TBI treatment is predicted.

The disadvantages of this method include:

- the use of indicators that do not allow to determine the nature of the humoral response and the degree of metabolic disturbances on the part of the LP / AOD system in brain injury;

- a traumatic method of collecting material - spinal puncture for 5-7 days, which is contraindicated for some types of damage.

Known patent No. 2209432 (Published: 07/27/2003) "A method for predicting the occurrence of inflammatory complications in the acute period of traumatic brain injury", which provides for the determination of the humoral response simultaneously in cerebrospinal fluid and blood, characterized in that the cytokine response of the pro-inflammatory cytokines of interleukin is determined as a humoral response -1 and -6, with proinflammatory cytokines of interleukin-1 in cerebrospinal fluid from 300 pg / ml to 1000 pg / ml and blood from 200 pg / ml to 400 pg / ml and interleukin-6 in cerebrospinal fluid from 100 pg / ml to 1000 PG / ml and blood from 1 00 pg / ml to 800 pg / ml predict the occurrence of intracranial inflammatory complications, and with proinflammatory cytokines of interleukin-1 in the cerebrospinal fluid from 100 pg / ml to 150 pg / ml and blood from 200 pg / ml to 700 pg / ml and interleukin- 6 in cerebrospinal fluid from 6.1 pg / ml to 10 pg / ml and blood from 10 pg / ml to 120 pg / ml predict the occurrence of extracranial inflammatory complications.

The disadvantages of this method include the following:

- the proposed method allows to predict the appearance of only inflammatory complications in about. period of traumatic brain injury (TBI), while traumatic brain disease (TBHM) should be considered as a form of the post-traumatic adaptation process, in which metabolic shifts that occur in the area of the injury (brain) lead to a violation of the integrity of the organ compartments of intact organs (O.S. Nasononkina, I. I. Deryabin [1987] and S. A. Georgiev et al. [1993]); those. the risk of inflammatory complications studied by the authors is only one aspect of a traumatic brain disease;

- for the study, a cerebrospinal fluid sampling is required, which is a rather traumatic procedure;

- the authors study the initial cytokine status in the cerebrospinal fluid after a head injury, which does not allow us to evaluate the dynamics of the humoral response (cytokines) associated with biochemical markers of oxidative stress (MDA) and the antioxidant defense component (superoxide dismutase);

- specific numbers of the levels of the studied cytokines are given, which implies the use of a specific enzyme immunoassay set (in their case, Cytelise) and limits the possibility of use.

Known patent No. 2196334 (Published: January 10, 2003) "A method for diagnosing a progressive course of a traumatic brain disease (TBHM) by examining blood serum", characterized in that the patient at the end of the recovery period using ELISA determines the level of TNF-α and IL-4 cytokines and at a TNF-α cytokine level above 16.8 pg / ml, and IL-4 cytokine below 97.88 pg / ml, a progressive course of TBHM is diagnosed.

The disadvantages of this method include the following:

- only the humoral response (cytokines) is investigated;

- only one of the variants of TBHM course is predicted - a progressive course;

- diagnosis is carried out at the end of the recovery period of the head injury, and in our case the diagnosis is carried out on the 1.2th day after the injury (acute period), i.e. thanks to the time-adjusted therapy, the progressive course of TBHM can be avoided altogether;

- specific numbers of levels of the studied cytokines are given, which implies the use of a specific enzyme-linked immunosorbent assay.

The closest in technical essence and selected as a prototype is a protected patent No. 2178179 (Published: 01/10/2002) "A method for predicting the course of traumatic brain disease (TBHM)."

The disadvantages of the prototype method are eliminated in the claimed invention.

The objective of the present invention is to reduce the morbidity of the method for predicting the course of traumatic brain disease in severe TBI, both combined and isolated.

This goal is achieved by the fact that in the first hour after a patient with a severe TBI, the patient is given Epocrine (the international non-proprietary name is epoetin alpha, the chemical name is recombinant human erythropoietin) at a dose of 10,000 IU, intravenously during the first 24 hours from the moment of injury. Before the administration of Epocrine and 24 hours after the administration of Epocrine, the content of cytokines in the blood serum is determined: IL-6, IL-10 (indicators of the humoral response of the body to injury); in addition, the content of malondialdehyde (MDA) (a product of lipid peroxidation) and the level of superoxide dismutase (SOD) (an enzyme that provides antioxidant protection) are determined in red blood cells.

Then, for each of the considered indicators, the relative change in its value after the introduction of Epocrine is determined (in percent) by calculating the ratio of the difference in the values of each of the considered indicators before and after the introduction of Epocrine to the value of the corresponding indicator before the introduction of Epocrine. The calculations are carried out according to the formula:

where A ₁ - the value of the indicator before the introduction of Epocrine,

And ₂ - the value of the indicator after the introduction of Epocrine,

P is the relative change in values.

With an increase in the content of IL-6 by more than 35% and IL-10 by less than 20%, MDA by more than 30%, against the background of an increase in the level of SOD by 45% or less, an unfavorable course of TBHM is predicted. As a result, the doctor is able to assess the dynamics of the humoral response (cytokines), coupled with biochemical markers of oxidative stress (MDA) and the antioxidant defense component (superoxide dismutase), and ultimately assess the body’s ability to restore cytokine balance and metabolic metabolism, and thereby, TBHM course prediction.

The technical result obtained as a result of using the claimed invention consists in increasing the accuracy and expanding the arsenal of tools used due to the fact that the result is evaluated as a percentage of the initial level, which does not limit the use of certain test systems; avoids complications of head injury due to time-adjusted therapy due to the fact that the diagnosis is carried out on the 1st day after the injury (acute period).

The theoretical premise of the claimed invention was our research to assess the importance and the relationship between the severity of TBHM and changes in the concentration of interleukin-6, interleukin-10, the product of LPO (MDA), the component of AOD (superoxide dismutase) in response to the introduction in the acute period of severe combined or isolated TBI drug recombinant human erythropoietin (Epocrine), leading to a normalization of the balance between pro- and anti-inflammatory cytokines and a decrease in the activation of LPO processes.

Injury disrupts brain activity due to both primary (biomechanical factors) and subsequent secondary damage (activation of pathophysiological cascades). Secondary damage encompasses many complex biochemical and cellular processes that exacerbate the severity of primary damage (Dafin F. Mureshanu, 2007). These include changes in the cytokine balance, activation of lipid peroxidation processes and components of the body's antioxidant defense.

It has been established that a number of factors are essential in the development of immune responses in the central nervous system: the state of the BBB, the level of antigenic representation in brain tissue and the level of cell adhesion to the endothelium of the brain vessels, activation of T-lymphocytes, which may have a polyclonal character, a lack of control systems, and disruption of mechanisms tolerance and control of immune responses due to the imbalance of activation and suppressor cytokines, their soluble receptors and inhibitors (Gusev E.I. et al., 1998; Fabry.et al., 1994). Cytokines are designed to ensure the adequacy of responses by regulating intercellular interactions (Akmaev I.G., 1997). According to Scares et al. (1995) the balance between pro-inflammatory and inhibitory, anti-inflammatory cytokines is critical in determining the severity of the neuro-autoimmune process within the central nervous system, which contributes to the progression of damage in brain injury and supports the chronic inflammatory process.

At the same time, activation of lipid peroxidation processes is a key link in neuronal death during brain damage (Kryzhanovsky GN, 1997). Activation of LPO processes is a general response of the brain to injury during head injury (Guidelines for craniocerebral injury. Edited by Acad. RAMS A.N. Konovalova - M. - 1998. - P.461). It is a vivid indicator of the degree of metabolic disturbance and the severity of destructive processes both in the body as a whole and in the brain tissue (V. A. Rozanov, V. A. Tsepkolenko, L. E. Klaupik. Modern ideas about the pathogenesis of irreversible damage to nerve cells with traumatic brain injury // Journal of Neurosurgery named after NN Burdenko, 1998, No. 2. P.37-41).

A number of studies indicate the interaction of the components of the cytokine network and lipid peroxidation products in the secondary damage caused by TBHM. So pro-inflammatory cytokines enhance the microbicidal nature of mononuclear cells due to the induction of the synthesis of superoxide and nitroxide radicals (Ketlinsky S.A., Kalinina N.M., 1995). On the other hand, the anti-inflammatory cytokines IL-4, IL-10, interleukin-13 (IL-13), TGF-beta, being antagonists of anti-inflammatory cytokines, have some opposite effects in the development of an inflammatory reaction (Freidlin I.S., 1995). They act as synergists in suppressing the production of superoxide and nitroxide radicals, acting on the enzyme involved in their formation.

The phenomenon of “oxygen explosion” of phagocytes, as the initiator of the inflammatory reaction, is the starting point for the excessive release of interleukins and other biologically active substances (Menshchikova EB et al., 2006; Pasechnik IN, 2002, Novik ES, 2007).

The blood test of the victim is carried out precisely on the 2nd day after the injury, since by this time, as a rule, a relative stabilization of the patient’s condition is observed due to removal from shock, improvement of the rheological properties of blood. At the same time, by this time, foci of ischemia are limited and foci of traumatic necrosis are formed in the brain, which allows only by this time to evaluate the functional capabilities of brain tissue (Kasumova S.Yu. Pathomorphology of craniocerebral injury // Neurotraumatology. Handbook. - Rostov- on-Don, 1999, p. 187-191). This allows you to evaluate the functionality of brain tissue that is not damaged irreversibly as a result of the trauma with minimal impact of processes in the body during the shock period.

Recombinant human erythropoietin (Epocrine) is approved for medical use by order of the Ministry of Health of the Russian Federation No. 212 of July 20, 1995 - glycoprotein, in its composition, biological and immunological properties, is identical to natural human erythropoietin. The recombinant human erythropoietin preparation exhibits neuroprotective properties in an experimental model of stroke and head injury. The drug reduces the volume of the damage zone and improves the functional outcome, which is possibly due to the suppression of the inflammatory response to damage (Hasselblatt et al., 2006). Sakanaka et al. (1998) found that erythropoietin can increase the activity of antioxidant enzymes such as superoxide dismutase, glutathione pyroxidase in neurons, thus protecting the brain parenchyma from damage due to ischemia. Its use for the treatment of cerebral ischemia is described (patent No. 2242991, published December 27, 2004). Calapai et al. (2000) and Sasaki (2000) suggested that erythropoietin may exhibit a neuroprotective effect by decreasing NO-mediated formation of free radicals or counteracting their toxicity. Chen et al. (2007) in their study on a model of an animal with a brain injury found that the introduction of recombinant erythropoietin can reduce the inflammatory response in the brain after traumatic injury and this may be one of the mechanisms by which recombinant erythropoietin improves treatment outcomes. Given that the course of TBHM depends on the degree of balance between pro-inflammatory and anti-inflammatory cytokines in the brain tissue (Soares et al., 1995) and on the severity of metabolic metabolic changes in the LPO and AOZ systems (Romodanov A.P., Kopyev O.V., Pedachenko EG et al. Pathogenetic substantiation of periods of traumatic brain disease // Journal of Neurosurgery named after N.N. Burdenko, 1990, No. 6, pp. 10-13), the dynamics of changes in these indicators can serve as objective laboratory evaluation criteria metabolic shifts during T BGM.

The method is as follows.

After a preliminary examination of the victim, including clinical and laboratory tests, the patient is taken blood from the ulnar vein with a needle with a wide lumen without a syringe to determine the level of cytokines. To obtain plasma, blood samples are centrifuged for 15 minutes at 3000 rpm. Erythrocyte mass and blood plasma are obtained, which are collected and stored at a temperature of + 4 ° C.

These studies are carried out according to the following methods.

Determination of the quantitative concentration of IL-6 and IL-10 cytokines in the blood is carried out by a method based on the solid-phase "sandwich" variant of enzyme-linked immunosorbent assay. Specific reagents of the kit are monoclonal antibodies adsorbed on the surface of the holes of a collapsible polystyrene plate.

The research methodology is the same for the quantitative determination of IL-1 beta, IL-6, TNF-alpha, IL-10. At the first stage of analysis, test and control samples are incubated in wells with immobilized antibodies. Unbound material is removed by washing. The bound cytokine interacted during incubation with conjugate No. 1 (antibodies to a specific human cytokine with biotin). Next, unbound conjugate No. 1 is removed by washing. In the third stage, the bound conjugate No. 1 interacted during incubation with conjugate No. 2 (streptavidin with horseradish peroxidase). Unbound conjugate is also removed and the amount of bound conjugate No. 2 is determined by color reaction using a horseradish-hydrogen peroxide peroxidase substrate and chromogen-tetramethylbenzidine. The reaction is stopped by the addition of a stop reagent and the optical density of the solutions in the wells is measured at a wavelength of 450 nm. The intensity of yellow staining is proportional to the amount of interleukin contained in the sample.

To determine the level of IL-6, IL-10, use IFA-Best reagent kits of Vector-Best CJSC (Novosibirsk). Measurements are taken using a Uniplan 2005 vertical spectrophotometer. The quantitative content of cytokines is expressed in PCG / ml.

Determination of the content of malondialdehyde (MDA) in blood red blood cells is carried out according to the method of I.D. Stalnaya and T.D. Gorishvili (Steel I.D., Gorishvili T.D. Method for the determination of malondialdehyde using thiobarbituric acid. - In: Modern methods in biochemistry. - M .: "Medicine", 1977, p.66-68), which is based on the formation of a colored trimethyl complex of MDA with two molecules of 0.68% thiobarbituric acid. To 1 ml of 1% hemolysate was added 1 ml of a 33% trichloroacetic acid solution and 1 ml of a 0.75% TBA solution. Samples were placed in a boiling water bath at 100 ° C for 15 minutes. After cooling, the samples were centrifuged at 3000 rpm. The optical density of the solution was measured on a FEC at a wavelength of 535 nm in a cuvette with a layer thickness of 1 cm against distilled water.

The number of TBA-active products was calculated by the formula:

C-D / KlV,

where D is the optical density of the sample;

K is the molar coefficient equal to 1.56 · 10 ⁵ mol ^-1 cm ^-1 ;

l is the thickness of the cell;

V is the sample volume.

The content of MDA in the hemolysate is expressed in nmol / mg of hemoglobin.

Determination of the content of intracellular superoxide dismutase is carried out according to the method of Orphans (Sirota T.V. A new approach to the study of the process of autooxidation of adrenaline and its use for measuring the activity of superoxide dismutase // Vopr. Medical Chemistry, 1999, No. 3, pp. 14-15). The principle of the method for determining intracellular SOD is based on its ability to inhibit the reduction of nitrotetrazolium blue (NTS) during the autooxidation of adrenaline to adrenochrome in an alkaline environment under the conditions of generation of a superoxide anion radical.

To 1 ml of 1% hemolysate add 250 μl of 96% ethyl alcohol and 150 μl of chloroform, vigorously shake until complete precipitation of hemoglobin, which prevents determination. Centrifuged at 3000 rpm for 10-15 minutes.

To 3.5 ml of 50 mmol Na-carbonate buffer (pH 10.55) add 100 μl of supernatant erythrocyte hemolysate with precipitated hemoglobin (50 μl of plasma), 0.2 ml of an aqueous HTC solution (1: 1v: v) and 50 μl 0.1% solution of adrenaline, mix thoroughly. Incubate in a water thermostat at + 27 ° C for 10 minutes using a stopwatch. A purple color develops. The optical density of the experimental samples is measured at a wavelength of 540 nm against the control sample. Instead of biosubstrate, an appropriate amount of distilled water is added to the control. SOD activity is calculated by the formula:

T% = (E _to -E _op / E _to ) · 100%,

where T% is the percentage of inhibition of the recovery reaction of the NTS;

E _to - the optical density of the control sample;

E _op - the optical density of the experimental sample.

A 50% inhibition of the rate of NTS recovery is taken as a standard unit of enzyme activity.

SOD _{(for hemolysate)} = T% / 50% · V · t · c,

where V is the volume of the biosubstrate (ml);

t is the incubation time (min);

c - hemoglobin concentration in 1 ml of hemolysate (g / l).

SOD activity is expressed in conventional units / min · mg Hb.

After blood sampling, Epocrine at a dose of 10,000 ME is administered intravenously to the patient. 24 hours after the administration of Epocrine, venous blood is re-taken from the patient, in which the concentration of the same parameters is again determined.

Then, for each of the considered indicators, the relative change in its value after the introduction of Epocrine is determined (in percent) by calculating the ratio of the difference in the values of each of the considered indicators before and after the introduction of Epocrine to the value of the corresponding indicator before the introduction of Epocrine. The calculations are performed according to the formula:

where A ₁ - the value of the indicator before the introduction of Epocrine,

And ₂ - the value of the indicator after the introduction of Epocrine,

P is the relative change in values.

With an increase in the content of IL-6 by 35% and higher and IL-10 by no more than 20%, MDA by 30% and higher, against the background of an increase in SOD by no more than 45%, an unfavorable course of TBHM is predicted.

Based on the results of the prognosis, the patient is corrected for an intensive care course.

The performance of the proposed method is confirmed by the following clinical examples.

Example 1

Patient Peninsula, 36 years old, medical history No. 37088, was admitted to the anesthesiology and intensive care unit of the MLPU GBSMP No. 2 of Rostov-on-Don for an open head injury, severe brain contusion with compression of the brain with an intracerebral hematoma, and a bruised head wound. Upon receipt of the state cr. heavy, skin and visible mucous membranes of a pale color, blood pressure = 100/60 mm Hg, pulse = 90 beats. in min, BH = 16 in min, level of consciousness - coma I, pupils D = S, photoreaction is reduced, horizontal nystagmus, muscle tone is reduced. According to computed tomograms of the brain (CT): intracerebral medial hematoma on the right, subarachnoid hemorrhage. An ultrasound (US) examination of the abdominal organs revealed no pathology; free fluid was not determined. The patient was prescribed an intensive care complex, which includes hemostatic, dehydration measures, as well as inhalation of moistened oxygen through a face mask.

Immediately after admission to the hospital, on the first day from the moment of injury, after a preliminary examination of the victim, including clinical and laboratory tests, a blood sampling was performed from a peripheral vein, in which the parameters were determined: IL-6 = 145.20 pg / ml, IL-10 = 5.84 pg / ml, MDA = 1.66 nmol / mg Hb, SOD = 1.86 units / min · mg Hb. After blood sampling, the patient was intravenously given Epocrine at a dose of 10,000 ME diluted in 10 ml of isotonic NaCl solution. 24 hours after the administration of Epocrine, venous blood was taken again from the patient, in which the value of the same indicators of cytokines, LPO and AOZ system was again determined. The following values were obtained: IL-6 = 197.18 pg / ml, IL-10 = 6.97 pg / ml, MDA = 2.17 nmol / mg Hb, SOD = 2.68 units / min · mg Hb. Then, according to the formula proposed above, the changes in these indicators after the introduction of Epocrine were determined. Calculations showed that the following change in each of the indicators occurred: an increase in IL-6 and IL-10 by 36% and 19.4%, respectively, an increase in MDA by 30.7%, and an increase in SOD by 44%. The patient was given a prognosis of an adverse course of TBHM.

The course of the disease proceeded in accordance with the unfavorable prognosis and was complicated by the development of PON, sepsis, and bilateral pneumonia. A mechanical ventilation lasting 30 days was performed. For 10 days, the patient was in coma 1, then his condition was regarded as apalic syndrome. After 21 days, the patient was transferred from the ARO to the neurosurgery department.

Example 2

Patient Zh-ev, 18 years old, medical history No. 49113, was admitted to the Department of Anesthesiology and Intensive Care MLPU GBSMP No. 2 of Rostov-on-Don due to an emergency surgery, severe brain contusion, traumatic subarachnoid hemorrhage, left occipital bone fracture, abrasions of the face. Upon receipt of the state cr. heavy, skin and visible mucous membranes of a pale color, blood pressure = 100/60 mm Hg, pulse = 98 beats. in min, BH = 16 in min, level of consciousness - coma I, pupils D = S, photoreaction is reduced, muscle tone is moderately reduced. According to computed tomograms of the brain (CT): in the left frontal region, the hemorrhagic impregnation site is about 2 × 0.5 cm, NAO, a linear fracture of the occipital bone on the left without pronounced displacement of fragments. An ultrasound (US) examination of the abdominal organs revealed no pathology; free fluid was not determined. The patient was prescribed an intensive care complex, which includes hemostatic, dehydration measures, as well as inhalation of moistened oxygen through a face mask. Immediately after admission to the hospital, on the first day from the moment of injury, after a preliminary examination of the victim, including clinical and laboratory tests, a patient was taken from a peripheral vein for blood, in which the following parameters were determined: IL-6 = 28.21 pg / ml, IL-10 = 6.33 pg / ml, MDA = 1.57 nmol / mg Hb, SOD = 2.15 units / min · mg Hb. After blood sampling, the patient was intravenously given Epocrine at a dose of 10,000 ME diluted in 10 ml of isotonic NaCl solution. 24 hours after the administration of Epocrine, venous blood was taken again from the patient, in which the value of the same indicators of cytokines, LPO and AOZ system was again determined. The following values were obtained: IL-6 = 37.97 pg / ml, IL-10 = 7.65 pg / ml, MDA = 2.03 nmol / mg Hb, SOD = 3.14 units / min · mg Hb. Then, according to the formula proposed above, the changes in these indicators after the introduction of Epocrine were determined. The calculations showed that the following change in each of the indicators occurred: an increase in IL-6 and IL-10 by 34.6% and 20.9%, respectively, an increase in MDA by 29.3%, an increase in SOD by 46%. The patient was given a prognosis of a favorable course of TBHM.

The course of the disease proceeded in accordance with the favorable prognosis: on the 3rd day the patient left the coma, on the 7th day the patient was transferred from the ARC to the neurosurgery department. During the observation period in the ARC, the patient had no complications.

In order to study the effectiveness of the proposed method for predicting the course of TBHM in the anesthesiology and intensive care unit of BSMP-2 in Rostov-on-Don, according to the claimed method, 30 people with severe combined and isolated head injury were examined. Of these, 19 patients showed an increase in the level of IL-6 by 35% and higher, IL-10 by 20% or lower, the rate of MDA red blood cells increased by more than 30% against the background of an increase in SOD by 45% or less. An adverse course of TBHM was observed in these patients.

Thus, the claimed method allows with high accuracy to predict the outcome of TBHM with the least traumatic study and to make a selection or adjustment of intensive care.

The inventive method has been tested in clinical practice and can be recommended for implementation in intensive care hospitals.

Claims (1)

A method for predicting the course of traumatic brain disease (TBHM), which involves examining a biological fluid with a determination of the concentration of malondialdehyde (MDA) in it, characterized in that venous blood is collected from the victim on the first day after the injury, in which the content is determined in addition to determining the MDA value in the blood serum of the cytokines IL-6, IL-10 and the level of superoxide dismutase (SOD), after blood sampling, the patient is injected with recombinant human erythropoietin at a dose of 10,000 IU, after 24 hours after the introduction of recombinant human erythropoietin, venous blood is retrieved from the patient, in which the values of IL-6, IL-10, MDA of red blood cells and the level of SOD are again determined, the ratio of the difference in the values of each of the considered parameters before and after the introduction of recombinant human erythropoietin to the value of the corresponding indicator before the introduction of recombinant human erythropoietin and with an increase in the content of IL-6 by 35% or higher, IL-10 by 20% or lower, MDA of red blood cells - by more than 30%, SOD level by 45% or less unfavorable course of TBHM.