RU2795206C1 - Method of early prediction of postoperative cognitive dysfunction in ihd patients undergoing coronary artery bypass surgery - Google Patents

Abstract

FIELD: medicine.

SUBSTANCE: invention relates to cardiac surgery, neurology, anesthesiology and intensive care, clinical immunology, and can be used for early prediction of the development of postoperative cognitive dysfunction in patients with coronary artery disease who underwent coronary artery bypass grafting. The determination of indicators of innate immunity IFNγ, IL-10 and neuropeptides NSE, S100B in the blood serum is carried out. At the following serum values before surgery: IFNγ more than 16.46 pg/ml; after surgery: IFNγ more than 14.4 pg/ml, NSE more than 5.56 ng/ml; 24 hours after surgery: IL-10 more than 19.89 pg/ml and S100B more than 92.63 pg/ml there is an unfavorable prognosis for a high risk of developing postoperative cognitive dysfunction.

EFFECT: method provides the possibility of assessing the prognosis in patients with coronary artery disease who underwent coronary artery bypass surgery, allowing to assess the risk of developing postoperative cognitive dysfunction at an early stage by determining and analyzing the serum level of IFNγ, NSE, S100B, IL-10.

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Description

The invention relates to medicine, namely to cardiac surgery, neurology, anesthesiology and intensive care, clinical immunology, being a method for early diagnosis of postoperative cognitive dysfunction in patients with coronary heart disease (CHD) who underwent coronary artery bypass grafting.

Continuous improvement of myocardial revascularization techniques, anesthetic and perfusion support, as well as monitoring of vital functions during and after these operations has led to a decrease in the incidence of severe neurological disorders and an increase in interest in milder, at first glance, postoperative cognitive impairments. which nevertheless lead to a decrease in the quality of life of patients, disability and an increase in the length of stay of patients in the hospital [Aleksandrovich Yu.S. et al., 2019]. These include postoperative cognitive dysfunction (POCD).

It is difficult to estimate the frequency of occurrence of this complication, since for a long time there were no clear diagnostic criteria, and it is often not diagnosed in a hospital, but is noticed only by relatives of the patient, who becomes forgetful, sometimes disoriented in space and time. According to some reports, the frequency of this complication can reach from 6 to 56% on days 42-84 after surgery [Polushin Yu.S. et al., 2019).

In connection with the growing interest in the problem of postoperative cognitive dysfunction, as well as the complexity of its diagnosis associated with errors in the use and evaluation of neuropsychological testing data, various biomarkers of damage and predictors of this complication are being actively searched for. These metrics can help clinicians diagnose, categorize patients at risk, and provide guidance to help elucidate the immune mechanisms underlying POCD, which is an important prospect for the development of different drugs that can target different pathogenesis for prevention or treatment. The literature presents scattered data on the participation in the implementation of neuroinflammation, and as a result, in the formation of postoperative cognitive dysfunction, such indicators as interferons, primarily interferon gamma (IFNγ), interleukins, neuropeptides.

From the above information, it follows that there are no unambiguous and systematized data on the role of innate immunity disorders in the pathogenesis of postoperative cognitive dysfunction.

Method RU 2219840 C2 for determining the long-term prognosis of neurocognitive function in patients undergoing coronary bypass grafting consists in assessing cerebral blood flow by SPECT before surgery and after 1 month, which is a disadvantage of the method, t.to. does not imply early identification of the risks of developing POCD.

The closest adopted for the prototype is the method EN 2645938 C1, which consists in predicting postoperative cognitive dysfunction in women after hysterectomy by examining the cognitive status and serum level of S100B protein in the preoperative and early postoperative period. The disadvantage of this method is the lack of a comprehensive laboratory study, which reduces the sensitivity of the technique, repeated cognitive testing in the early postoperative period, on the second day after surgery, which contradicts modern recommendations for the diagnosis of POCD, as well as an assessment of the risk of developing POCD with other surgical intervention than aortocoronary shunting.

The objective of the invention is to create an early, more informative and specific method for assessing the risk of developing postoperative cognitive dysfunction in patients with coronary artery disease who underwent coronary artery bypass surgery due to an in-depth analysis of a complex of immunological parameters.

To solve the problem in the method for early diagnosis of postoperative cognitive dysfunction in patients with coronary artery disease who underwent coronary artery bypass surgery, according to the invention, venous blood is taken from patients with coronary artery disease who underwent coronary artery bypass surgery on the day of surgery before and after the intervention and 24 hours after the day for laboratory determination of the serum level of interferon gamma (IFNγ), neuron-specific enolase (NSE), protein C100B (S100B), interleukin 10 (IL-10). With serum values before surgery: IFNγ more than 16.46 pg/ml; after surgery: IFNγ more than 14.4 pg/ml, NSE more than 5.56 ng/ml; 24 hours after surgery: IL-10 more than 19.89 pg/ml and S100B more than 92.63 pg/ml establish an unfavorable prognosis for a high risk of developing postoperative cognitive dysfunction.

EFFECT: developed a new method for assessing the prognosis in patients with coronary artery disease who underwent coronary artery bypass surgery, which allows at an early stage to assess the risk of developing postoperative cognitive dysfunction by determining and analyzing the serum level of interferon gamma (IFNγ), neuron-specific enolase (NSE), protein C100B (S100B). ), interleukin 10 (IL-10).

The claimed method was developed on the basis of the TSMU of the Ministry of Health of Russia and tested on the basis of the medical center of the FGAEI HE FEFU. The study included, according to the inclusion criteria and taking into account the exclusion criteria, 100 male and female people from 64 to 74 years old with coronary artery disease, who underwent CABG under CPB, and 30 relatively healthy elderly people (control group). All examined patients were tested according to the Montreal Cognitive Assessment Scale (MoCa test) and MMSE before CABG, on the 7th day after CABG and 31-40 days after surgery. The control group was tested once. Based on the MoCa test and MMSE, two groups were distinguished. Group I - patients without postoperative cognitive dysfunction - these are 56 people with deterioration in MoCa test and MMSE 31-40 days after CABG less than 2 points (1.3±0.06) in 2 tests, and group II included 44 patients with postoperative cognitive dysfunction with worsening of this indicator by more than 2 points (3.0±0.2) in 2 tests 31-40 days after CABG. Patients of groups I and II differed little in age, gender, time of surgery, cardiopulmonary bypass and aortic clamping. All patients signed an agreement on personal consent to undergo all stages of the study.

For the first time, a comprehensive assessment of the system of cytokines, metalloproteinases, their inhibitors and neurospecific proteins, concomitant risk factors was carried out with an analysis of their relationship in patients with postoperative cognitive dysfunction after coronary artery bypass grafting:

- assessed general clinical data in patients with coronary heart disease with postoperative cognitive dysfunction, after CABG;

- the most valuable markers for the development of postoperative cognitive dysfunction were identified;

- Serum levels of interferon gamma (IFNγ), neuron-specific enolase (NSE), protein C100B (S100B), interleukin 10 (IL-10) were determined by the sandwich method of solid-phase ELISA using reagents from R&D Systems (USA).

According to the results of studies in the development of the proposed method, immunological markers of a high risk of developing postoperative cognitive dysfunction in patients with coronary artery disease after CABG were identified.

To identify risk markers for the development of postoperative cognitive dysfunction, the following were performed:

1. Venous blood sampling was carried out in patients with coronary artery disease who underwent CABG immediately before surgery, immediately after and 24 hours after surgery for laboratory determination of the serum level of interferon gamma (IFNγ), neuron-specific enolase (NSE), protein C100B (S100B), interleukin 10 (IL-10).

2. Comprehensive monitoring of patients with coronary artery disease was carried out in the intra- and postoperative period.

3. Patients were tested using the Montreal Cognitive Assessment Scale (MoCa test) and MMSE before CABG, on the 7th day after CABG and 31-40 days after surgery.

With serum values before surgery: IFNγ more than 16.46 pg/ml; after surgery: IFNγ more than 14.4 pg/ml, NSE more than 5.56 ng/ml; 24 hours after surgery: IL-10 more than 19.89 pg/ml and S100B more than 92.63 pg/ml establish an unfavorable prognosis for a high risk of developing postoperative cognitive dysfunction. The method is carried out as follows.

From a patient undergoing coronary artery bypass surgery, venous blood is taken for laboratory determination of the serum level of interferon gamma (IFNγ), neuron-specific enolase (NSE), protein C100B (S100B), interleukin 10 (IL-10). Blood sampling is performed before surgery, immediately after surgery, and 24 hours after surgery, since these periods allow us to assess the dynamics of the immune response and to conduct an early assessment of the development of neuroinflammation.

The content of IFNγ was assessed in blood serum by a quantitative method of solid-phase ELISA using Human IFN-gamma DuoSet ELISA kits (catalog number DY285B (R&D Systems, USA). The content of interferon gamma was expressed in picograms per milliliter (pg/ml), the sensitivity of the methods used was 1 pg/ml The control values were taken as the results of similar tests carried out in a group of healthy people.Blood was taken immediately before the operation and immediately after it.

S100B content was assessed in blood serum by quantitative solid-phase ELISA using Human S100B DuoSet ELISA kits (catalog number DY1820-05 (R&D Systems, USA). S100B protein content was expressed in picograms per milliliter (pg/ml), the sensitivity of the methods used was 1 pg/ml The results of similar tests carried out in a group of healthy people were taken as control values.Blood was taken 24 hours after the operation.

The content of NSE was assessed in blood serum by a quantitative method of solid-phase ELISA using Human Enolase 2/Neuron-specific Enolase DuoSet ELISA kits (catalog number DY5169-05 (R&D Systems, USA). The content of neuron-specific enolase was expressed in nanograms per milliliter (ng/ml), the sensitivity of the applied methods was 1 pg/ml For control values were taken the results of similar tests conducted in a group of healthy people.Blood was taken immediately after surgery.

The content of IL-10 was assessed in blood serum by a quantitative method of solid-phase ELISA using Human IL-10 DuoSet ELISA kits (catalog number DY217B (R&D Systems, USA). The content of interleukin 10 was expressed in picograms per milliliter (pg/ml), the sensitivity of the methods used was 1 pg /ml For the control values were taken the results of similar tests conducted in a group of healthy people.Blood was taken 24 hours after surgery.

Based on the results of a comprehensive study, a prognostic conclusion is made. With serum values before surgery: IFNγ more than 16.46 pg/ml; after surgery: IFNγ more than 14.4 pg/ml, NSE more than 5.56 ng/ml; 24 hours after surgery: IL-10 more than 19.89 pg/ml and S100B more than 92.63 pg/ml establish an unfavorable prognosis for a high risk of developing postoperative cognitive dysfunction.

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

Example 1: A patient with coronary artery disease was admitted to the hospital with indications for CABG. Venous blood sampling was performed immediately before surgery, immediately after surgery, and 24 hours after CABG. According to laboratory studies, the level of IFNγ before surgery: 13.44 pg/ml; after surgery: 11.2 pg/ml; NSE after surgery 4.12 ng/ml; IL-10 24 hours after surgery 17.07 pg/ml; S100B 24 hours after surgery 80.1 pg/ml. Based on the data obtained, a low risk of developing postoperative cognitive dysfunction was established. According to the results of neurocognitive testing after 31 days, there were no signs of neurocognitive dysfunction.

Example 2: A patient with coronary artery disease was admitted to the hospital with indications for CABG. Venous blood sampling was performed immediately before surgery, immediately after surgery, and 24 hours after CABG. According to laboratory studies, the level of IFNγ before surgery: 19.41 pg/ml; after surgery: 15.33 pg/ml; NSE after surgery 6.33 ng/ml; IL-10 24 hours after surgery 20.02 pg/ml; S100B 24 hours after surgery 153.33 pg/ml. Based on the data obtained, a high risk of developing postoperative cognitive dysfunction was established, and active preventive activities were initiated to prevent the development of POCD. According to the results of neurocognitive testing after 31 days, the patient showed moderate changes, further dispensary observation by a neurologist and work with a rehabilitation specialist were recommended.

List of sources:

1. Aleksandrovich Yu.S., Akimenko T.I., Pshenisnov K.V. Postoperative cognitive dysfunction - is it a problem for the anesthesiologist-resuscitator? // Bulletin of anesthesiology and resuscitation. 2019. No. 4. URL: https://cyberleninka.ru/article/n/posleoperatsionnaya-kognitivnaya-disfunktsiya-yavlyaetsya-li-ona-problemoy-dlya-anesteziologa-reanimatologa (date of access: 06/30/2022).

2. Polushin Yu.S., Polushin A.Yu., Yukina G.Yu., Kozhemyakina M.V. POSTOPERATIVE COGNITIVE DYSFUNCTION - WHAT WE KNOW AND WHERE TO MOVE NEXT. Bulletin of anesthesiology and resuscitation. 2019; 16(1): 19-28. https://doi.org/10.21292/2078-5658-2019-16-1-19-28.

3. Safavynia S.A., Goldstein R.A. The Role of Neuroinflammation in Postoperative Cognitive Dysfunction: Moving From Hypothesis to Treatment. Front Psychiatry. 2019.I.9:752. doi:10.3389/fpsyt.2018.00752.

Claims (1)

A method for early prediction of the development of postoperative cognitive dysfunction in patients with coronary artery disease who underwent coronary artery bypass surgery, including the determination of innate immunity indicators IFNγ, IL-10 and neuropeptides NSE, S100B in blood serum, characterized in that with serum values before surgery: IFNγ more than 16, 46 pg/ml; after surgery: IFNγ more than 14.4 pg/ml, NSE more than 5.56 ng/ml; 24 hours after surgery: IL-10 more than 19.89 pg/ml and S100B more than 92.63 pg/ml establish an unfavorable prognosis for a high risk of developing postoperative cognitive dysfunction.