RU2542434C1 - Method for prediction of degree of risk of haemolytic complications following coronary bypass surgery - Google Patents

Abstract

FIELD: medicine.

SUBSTANCE: preoperative blood hemopoietins are measured by describing an amplitude, a time of development and a membrane potential recovery rate associated with Ca²⁺-induced erythrocyte hyperpolarising response (HPR); blood concentrations of erythropoietin (EPO) and tumour necrosis factor-α (TNF-α) are also determined. If they are found to belong to respective confidential intervals, the postoperative blood free haemoglobin concentration Y is determined by formula. If Y appears to excess 40 mg/dl, a high risk of postoperative haemolytic complications is predicted.

EFFECT: enabling quantitative assessment of prediction of degree of manifestation of postoperative haemolysis in the patient.

4 tbl, 2 ex

Description

The invention relates to the field of medicine, cardiac surgery, perfusiology, cardiology, resuscitation and can be used for preoperative prediction of the risk of developing hemolytic complications after coronary artery bypass grafting in cardiopulmonary bypass.

Despite the half-century history of the development of cardiac surgery, the problem of intravascular hemolysis in cardiopulmonary bypass remains still relevant. It is important to note that to date, the use of the least traumatic and most biocompatible perfusion modules still does not completely exclude the progressive increase in hemoglobinemia during operations on a stopped heart. Moreover, the severity of this pathophysiological reaction varies even when using identical perfusion equipment, which indicates the important role of the initial structural and metabolic properties of red blood cells in the processes of their destruction during extracorporeal perfusion associated with nonphysiological shear deformation, complement-dependent lysis, hyperoxia and hypothermia. Given that massive intravascular hemolysis can induce dysfunction of various organs (primarily kidneys) and the development of multiple organ failure in the early postoperative period, the preoperative prediction of the level of postperfusion hemoglobinemia based on the assessment of the properties of red blood cells seems to be extremely important, since it allows the primary prevention of hemolytic disorders.

A known method of preoperative prediction of the severity of intraoperative hemolysis in cardiac patients based on an analysis of the conditions for the upcoming operation. Take into account the type of equipment used, the estimated duration of IR and perfusion temperature, the intensity of the coronary suction (depends on the features of operative access), the possibility of transfusion of blood products. The lower the perfusion temperature and the longer its duration, the greater the severity of hemolysis; the use of oxygenators “D-902” and “Gish Vision” forms the most significant increase in free hemoglobin, the use of donated blood preparations does not significantly affect the severity of hemolysis [1]. In addition, the use of centrifugal and roller pumps with incomplete occlusion is more preferable than roller pumps with full occlusion; silicone and glass have less hemolytic effect than polyvinyl chloride and teflon; The use of biocompatible coated highways has some advantages over uncoated systems [2]. The main drawback of this approach is that it is difficult to predict the final level of hemoglobinemia, since it is difficult to determine the contribution of all IR conditions, but most importantly, the method does not take into account the individual characteristics of the patient and the properties of red blood cells undergoing destruction in the extracorporeal circuit.

A known method for predicting the degree of hemolysis in patients of any category by assessing the resistance of red blood cells to the action of shear deformation in vitro, while various modifications of the method differ in the method of recording the severity of destructive processes. One of them is based on determining the deformability of cells after circulation of a suspension of red blood cells in a closed circuit - the greater the decrease in their deformability, the more pronounced hemolysis is expected in a patient [3]. Another method is carried out by decreasing the number of red blood cells after mechanical action or by changing the ratio of intra- and extracellular hemoglobin after it - the fewer cells remain after exposure to the stimulus or the greater the increase in extracellular hemoglobin after it, the greater the severity of the expected in vivo hemolysis is higher [4]. Meanwhile, the drawback of the methods is that the severity of hemolysis is predicted on the basis of assessing the resistance of red blood cells only to a mechanical factor, while cells in the extracorporeal circuit are exposed to several stimuli (as described above).

There is a method of assessing the functional state of the body in patients of any category by measuring the in vitro hemolytic resistance of red blood cells to hydrochloric acid, which reflects the state of the lipid phase of the red blood cell membrane (permeability and chemical composition). Thanks to the erythrocyte resistance analyzer, the parameters of cell acid lysis are determined and, using unique software, they are converted into hematological parameters, blood formation characteristics, activity of the sympathoadrenal system, thyroid-stimulating hormone and thyroid hormones in blood plasma, which are automatically compared with standard indicators of a healthy person, after which the system gives a conclusion about the functional state of the body [5]. The disadvantage of this method is the doubtful extrapolation of its results to the hemolysis process during IR, since in vivo red blood cells are not exposed to such low pH values, and a comprehensive analysis of the hormonal background, rather, gives an idea of the reactivity of the whole organism, and not about the resistance of red blood cells to direct cyto-destructive effect of the IR apparatus.

A known method for predicting postperfusion hemolysis in cardiosurgical patients with a deficiency of the intra-erythrocyte enzyme glucose-6-phosphate dehydrogenase: the greater the enzyme deficiency, the higher the hemoglobinemia after surgery with IR is higher [6]. The disadvantage of the method is its limited use only in patients with a hereditary deficiency of this enzyme (a form of hemolytic anemia), while in patients not suffering from hematological pathology, the role of this given property of cells in the mechanisms of the implementation of postperfusion hemolysis has not been studied.

Thus, all the above methods for predicting hemolysis, based on the assessment of the structural and metabolic properties of red blood cells before surgery, use only one of the many characteristics of the cell (mechanical or acid resistance, or enzyme activity) and have not been tested in patients with coronary heart disease (CHD) coronary bypass surgery. Meanwhile, the nature of the pathology determines the peculiarities of the violation of the morphofunctional and metabolic properties of red blood cells, which together determine the resistance of cells to a number of hemolysis-inducing factors IR.

The closest way to predict hemolytic complications by assessing the severity of hemolysis in patients with coronary artery disease after surgery with IR is a method consisting in a combined assessment of the mechanical, acid, osmotic resistance of red blood cells and their membrane permeability before surgery. It was shown that hemolytic complications, such as pronounced postperfusion hemolysis (more than 40 mg / dl), develop in patients with coronary artery disease with high permeability of the erythrocyte membrane, reduced acid and mechanical resistance of the cells, and a normal minimum osmotic resistance before surgery; moderate hemolysis (less than 40 mg / dl) - in patients with coronary artery disease with normal permeability of the erythrocyte membrane, normal acid, mechanical resistance of cells and a high value of the minimum osmotic resistance of erythrocytes before surgery [7]. Nevertheless, the revealed features of the preoperative properties of erythrocytes are only in the nature of associations, while the confidence intervals for the studied parameters in the compared groups of patients are not established and the indicators are not integrated into the mathematical regularity, using which it would be possible to predict the exact concentration of free hemoglobin in blood plasma after surgery.

A new technical task is to increase the accuracy and informativeness of the method, in which a quantitative assessment of the prognosis of the severity of hemolysis after surgery with IR is possible, based on a complex statistical analysis of many indicators of the peripheral unit of the erythron before surgery.

To solve the problem, in a method for predicting the risk of developing hemolytic complications after coronary artery bypass surgery in patients with cardiopulmonary bypass by assessing the condition of the peripheral erythron unit before surgery, the hematopoietins in the blood are evaluated before surgery, for which the amplitude, time of its development and rate of restoration of the membrane potential at Ca ²⁺ -induced hyperpolarization of the erythrocytes (GPO), concentration of erythropoietin (EPO) and tumor necrosis factor she-α (TNF-α) in the blood, and if they belong to their respective confidence intervals: amplitudes from 0.11 to 1.01 mV; the time of its development from 26.16 to 60.12 s, GPO from 0.49 to 0.91 meqN + / (min × l cells); EPO from 2.94 to 20.14 mIU / ml and TNF-α from 0.21 to 6.8 pg / ml, respectively, calculate the concentration of free hemoglobin in the blood after surgery Y according to the formula:

Y = 139.60-1.43 X _EPO -0.44 X _TNF -29.20 X _ΔE -38.64 X _V2 -0.90 X X _ΔT

where 139.60 is a constant for patients with coronary heart disease with a risk of developing severe hemoglobinemia;

1.43; 0.44; 29.20; 38.64 and 0.90 - numerical values are coefficients;

X _EPO - concentration of EPO in plasma (mIU / ml);

X _TNF - concentration of TNF-α in blood plasma (PG / ml);

X _ΔE is the amplitude of Ca ²⁺ -induced GPO of erythrocytes (mV);

X _V2 — rate of restoration of membrane potential in Ca ²⁺ -induced HPO of erythrocytes (meqH + / (min × l cells));

X _ΔT is the development time of the maximum value (amplitude) of the membrane potential in Ca ²⁺ -induced HPO of erythrocytes (seconds).

and with Y exceeding 40 mg / dl, a high degree of risk of developing hemolytic complications in the postoperative period is predicted.

The severity of hemolytic complications is directly proportional to the Y value. The calculated Y value is the concentration of free hemoglobin in the blood after surgery, expressed in mg / dl, and closely correlates with the actually observed level of hemoglobinemia after surgery (correlation coefficient 0.98; p <0.01 ) This formula reflects the relationship between factors quite well and explains 96% of the variation of the effective trait by the variation of factor variables.

Taking into account the fact that in order to use the regression equation, it is necessary to satisfy the requirement that the distribution of factor variables correspond to the normal law, then the developed formula can be applied only if factor variables vary within confidence intervals (at a level of statistical significance p <0, 05) established by the training sample:

- for the concentration of EPO in the blood (2.94; 20.14) mIU / ml;

- for the concentration of TNF-α in the blood (0.21; 6.8) pg / ml;

- for the amplitude of Ca ²⁺ -induced GPO of erythrocytes (ΔE) (0.11; 1.01) mV;

- for the rate of restoration of the membrane potential (V ₂ ) with Ca ²⁺ -induced GPO of erythrocytes (0.49; 0.91) meqN ⁺ / (min × l cells);

- for the time of development of the maximum value of the membrane potential (ΔT) with Ca ²⁺ -induced GPO of erythrocytes (26.16; 60.12) seconds.

When using values that go beyond the corresponding confidence intervals, the prognostic value of the formula may decrease.

The method is as follows.

In a patient diagnosed with coronary artery disease, who is scheduled to undergo coronary bypass surgery under IR conditions, the content of EPO and TNF-α in the blood and the parameters of Ca ²⁺ -induced GPO of red blood cells are determined before surgery - its maximum value, i.e. amplitude (ΔE), the time of its development (ΔT) and the rate of restoration of the membrane potential (V ₂ ). If each of the obtained values varies within the respective above confidence intervals, then these values are used to calculate the concentration of free hemoglobin in the blood after surgery according to the formula:

Y = 139.60-1.43 X _EPO -0.44 X _TNF -29.20 X _ΔE -38.64 X _V2 -0.90 X X _ΔT

The calculated Y value represents the concentration of free hemoglobin in the blood (mg / dl) expected in this patient after completion of the IR operation. If it exceeds 40 mg / dl, then a high degree of severity of intraoperative hemolysis is predicted with the development of highly probable hemolytic complications, the severity of which is directly proportional to the value of Y.

The initiation of intravascular hemolysis during IR operations is today an inevitable component of the patient's post-perfusion reactions to extracorporeal perfusion. Massive hemoglobinemia significantly impairs renal function due to obstruction of the renal tubules by coagulated hemoglobin, induction of free radical processes in the renal epithelium, and aggravation of renal ischemia due to the binding of nitric oxide (NO) molecules. Similarly, free hemoglobin mediates severe microcirculatory disorders in all tissues and organs, which is complemented by occlusion of microvessels with membrane fragments of lysed cells and potentiation of posthemorrhagic anemia. In this regard, the study and correction of intravascular hemolysis during operations with IR has become one of the main tasks of perfusion and resuscitation.

Among the contributing (exogenous) factors for the development of severe hemolysis, the features of perfusion equipment and the conditions of the operation are distinguished. The severity of hemoglobinemia increases with prolonged extracorporeal perfusions, with intensive coronary suction, deep hypothermia, high hematocrit and blood oxygenation during surgery, transfusion of donor red blood cells. Predisposing (endogenous) factors mainly include the presence of hereditary and acquired hemolytic anemia - thalassemia, sickle cell anemia, anemia due to a genetically determined deficiency of glucose-6-phosphate dehydrogenase, malaria and babesiosis. Meanwhile, the level of postperfusion hemoglobinemia varies significantly even in cardiosurgical patients who do not suffer from hematological pathology, operated on under approximately equal conditions. In this regard, there is an assumption that the severity of postperfusion hemolysis depends on the state of the peripheral erythron at the time of surgery, given that it would be possible to predict the severity of intravascular hemolysis after IR in the preoperative period.

The development of the proposed method for predicting the severity of intraoperative hemolysis in cardiac patients based on the analysis of the structural and metabolic status of red blood cells before surgery is based on the results of experimental and clinical studies. An in-depth clinical and laboratory examination of 90 coronary heart disease patients who underwent coronary bypass surgery, in which 1 h after completion of IR in the blood, the concentration of free hemoglobin was determined, and before the operation, a number of indicators of the structural and metabolic status of red blood cells and blood composition: the content of red blood cells, reticulocytes, fibrinogen, haptoglobin, erythropoietin necrosis factor-α tumor, and glycophorin a ⁺ glycophorin B ⁺ red blood cells, erythrocytes rigidity index, a phospholipid and cholesterol- th ratio, the relative content of inositol, phosphatidylserine, phosphatidylethanolamine and phosphatidic acid in the erythrocyte membrane, the activity of Na ⁺ / K ⁺ -adenozintrifosfatazy erythrocyte membrane, catalase activity in erythrocytes and indicators Ca ²⁺ -induced hyperpolarizing erythrocyte response (GAP).

Patients were included in the study, subject to the following criteria:

1. Men and women from 48 to 70 years old inclusive, suffering from coronary artery disease (angina pectoris) and undergoing coronary bypass surgery in the IR;

2. The written informed consent of the patient to participate in the study.

The exclusion criteria from the study were:

1. Exacerbation of chronic concomitant pathology;

2. The presence of hematological diseases (anemia, chronic leukemia);

3. The presence of acute respiratory disease 3 weeks before surgery;

4. Appointment of oxygen therapy courses, erythropoietin or iron preparations;

5. Performing operations combined with coronary artery bypass grafting (resection of an aortic or left ventricular aneurysm, correction of heart defects, removal of myxoma, surgery to restore blood flow through the carotid arteries and lower limb arteries);

6. The presence of infusion of red blood cells during perfusion;

7. The duration of the IR is more than 240 min;

8. Refusal of research.

The diagnosis of coronary heart disease (CHD) was established on the basis of complaints and medical history, electrocardiography, ultrasound of the heart, cardioventriculography, as well as scintigraphy and emission computed tomography of the myocardium. In the presence of hemodynamically significant stenosis of two or more coronary arteries (more than 75% of the cross-sectional area of the vessel) and / or complete occlusion of the trunk of the left coronary artery, a coronary bypass operation was prescribed.

Among IHD patients, males predominated, suffering from angina pectoris of functional class III, circulatory insufficiency of functional class II (NYHA) and grade 3 hypertension, which in the structure of the concomitant pathology mainly included diseases of the gastrointestinal tract (Table 1).

Extracorporeal perfusion was carried out on a Stokert IR apparatus (SORIN GROUP DEUTSCHLAND, Germany) equipped with roller pumps using disposable Quadrox membrane oxygenators (MAQUET AG, Germany). To fill the primary volume of the IR apparatus, physiological saline in a volume of 1200 ml and polyglucin 400 ml were used. The perfusion volumetric rate was calculated based on the perfusion index of 2.5 l / min / m ² and the patient’s body surface area. Extracorporeal perfusion was performed under normothermy conditions (36.09 ± 0.26 ° C) and antegrade cardioplegia using Custodiol solution (Dr. F. Koehler Chemie GmbH, Germany). The characteristic of the intraoperative period is given in table.2.

At the preoperative stage, IHD patients underwent antianginal therapy using prolonged nitrates (isosorbide-5-mononitrate), beta1-blockers (bisoprolol, metoprolol), Ca ²⁺ channel blockers (felodipine, amlodipine). Antihypertensive therapy with angiotensin-converting enzyme inhibitors (enalopril, spiropril, perindopril, fosinopril) and diuretics (spironolactone, indapamide, furosemide) was also carried out; antiplatelet agents (acetylsalicylic acid, clopidogrel) and anticoagulants (heparin, fraxiparin) were prescribed. Correction of lipid metabolism was carried out using statins (atorvastatin, simvastatin). In type 2 diabetes mellitus, hypoglycemic drugs (glibenclamide, glyclazide, metformin) were prescribed; with peptic ulcer of the stomach and / or duodenum - antiulcer therapy (omeprozole, ranitidine).

In the intraoperative period, patients with coronary artery disease received intravenous infusions of ketamine 5%, fentanyl 0.005%, promedol 2%, morphine 1%, diazepam 0.5%; dimedrol 1%, droperidol 0.25%, lidocaine 10%, atropine 0.1%, pentamine 5%, pipecuronium 0.2%, suxamethonium 2%, nitroglycerin 1%, heparin 5000 U / ml, ethamylate 12.5%, aminocaproic acid 5%, prednisone 2.5%, ceftriabol 1 g, sultamine 1.5 g, furosemide 1%. In some cases, according to the indications, adrenomimetics (adrenaline, dopmin, mesatone) or adrenergic blockers (metoprolol, albetor, ebronil), insulin, verapamil were administered.

The analysis of the above parameters of the structural and metabolic status of red blood cells and blood composition in patients with coronary artery disease before surgery in connection with the concentration of free hemoglobin in the blood 1 h after completion of the IR was performed. Venous blood taken from the ulnar vein was heparinized (50 U / ml), plasma was separated, and red blood cells were washed three times with physiological saline. The erythromass was used to assess the conductivity of the K ⁺ (Ca ²⁺ ) erythrocyte channels by detecting Ca ²⁺ -induced GPO, to measure the relative content of glycophorin A ⁺ and glycophorin B ⁺ red blood cells by luminescence microscopy, to determine the activity of catalase by the rate of decomposition of hydrogen peroxide , erythrocyte rigidity index by filtration method, erythrocyte membrane isolation to determine the relative content of inositol phosphate, phosphatidylserine, phosphatidylethanolamine and phosphatidic acid you are in the erythrocyte membrane, the activity of Na ⁺ / K ⁺ adenosine triphosphatase in it. In the blood plasma, the concentration of EPO and TNF-α was determined by enzyme-linked immunosorbent assay, haptoglobin by immunoturbodimetry, Klaus fibrinogen, free hemoglobin by the benzidine method. Whole blood was used to count red blood cells and reticulocytes by standard hematological methods.

The obtained values were subjected to regression analysis, taking as an effective variable (Y) the concentration of free hemoglobin in the blood of cardiac surgical patients after surgery, and the analyzed variables of the structural and metabolic status of red blood cells and blood composition in the preoperative period as X factor variables (X). Considering the requirement of a regression analysis on the use of a complex of related variables as a training sample (determined for the same patient) and the fact that the studies were carried out in blocks, several databases were formed, including a small number of factor variables, which made it possible to obtain several equations of multiple linear regression of the effective sign (table 3).

When analyzing the statistical parameters of the revealed patterns (Table 3), it becomes obvious that the most informative is equation No. 6, which describes the dependence of the severity of postperfusion hemoglobinemia on the concentration of EPO and TNF-α in the blood and the parameters of Ca ²⁺ -induced GPO of red blood cells before surgery, since the formula is significant at a level of statistical significance p <0.05, reflects quite well the relationship between factors (multiple correlation coefficient R = 0.98) and explains 96% of the variation of the effective sign by the variation of fa -valued variables (determination coefficient R ² = 0.96). In this regard, as a formula for predicting hemolysis after surgery, the following pattern was chosen:

Y = 139.60-1.43 X _EPO -0.44 X _TNF -29.20 X _ΔE -38.64 X _V2 -0.90 X X _ΔT

where 139.60 is a constant for patients with coronary heart disease with a risk of developing severe hemoglobinemia;

1.43; 0.44; 29.20; 38.64 and 0.90 - numerical values are coefficients;

X _EPO - concentration of EPO in the blood (mIU / ml);

X _TNF - concentration of TNF-α in the blood (pg / ml);

X _ΔE is the amplitude of Ca ²⁺ -induced GPO of erythrocytes (mV);

X _V2 — rate of restoration of membrane potential in Ca ²⁺ -induced HPO of erythrocytes (meqH ⁺ / (min × l cells));

X _ΔT is the development time of the maximum value (amplitude) of the membrane potential in Ca ²⁺ -induced HPO of erythrocytes (seconds).

Taking into account the requirement of a regression analysis on the conformity of the nature of the distribution of factor variables to the normal law, confidence intervals for factor variables were calculated (at a level of statistical significance p <0.05), within which the application of the obtained formula is true:

- for the concentration of EPO in the blood (2.94; 20.14) mIU / ml;

- for the concentration of TNF-α in the blood (0.21; 6.8) pg / ml;

- for the amplitude of Ca ²⁺ -induced GPO of erythrocytes (ΔE) (0.11; 1.01) mV;

- for the rate of restoration of the membrane potential (V ₂ ) with Ca ²⁺ -induced GPO of erythrocytes (0.49; 0.91) meqN ⁺ / (min × l cells);

- for the time of development of the maximum value of the membrane potential (ΔT) with Ca ²⁺ -induced GPO of red blood cells (26.16; 60.12) seconds (s).

It should be noted that a regression analysis between the amount of hemoglobinemia after surgery, the duration of IR and the maximum level of blood oxygenation during perfusion demonstrates a weak effect of these factors on hemolysis, since they determine only 20% of hemoglobinemia variability (determination coefficient R ² = 0.20; table .3, formula No. 1), which is much less than the determining effect of the initial (before surgery) condition of the peripheral erythron unit on the severity of intraoperative hemolysis (Table 3, formula No. 6).

As a result of the application of the proposed method, a close correlation was observed between the calculated and actually observed values of the concentration of free hemoglobin in the blood (correlation coefficient 0.98; p <0.01; Table 4); forecast accuracy was 93.6%.

Examples of the method

Example 1. Patient K., 63 g. Diagnosis: CHD. Angina of exertion of functional class III, post-infarction cardiosclerosis (2011), circulatory failure of functional class II NYHA, IHD duration of 7 years. Concomitant diseases: grade 3 hypertension, type 2 diabetes mellitus, gastric ulcer (remission), urolithiasis. The duration of cardiopulmonary bypass was 136 min, the average perfusion rate: temperature 36.08 ° C, the volumetric perfusion rate of 5.2 l / min, the intensity of coronary suction 651 ml / min, the level of blood oxygenation 158 mm Hg, hematocrit 26, 2%; there was no intraoperative transfusion of erythromass; red blood diseases were not observed in the last 6 months before surgery.

A study was carried out according to the proposed method B of blood taken before surgery, the concentration of EPO and TNF-α, the parameters of Ca ²⁺ -induced GPO of erythrocytes ΔE, V ₂ and ΔT were respectively: 18.50 mIU / ml; 3.51 pg / ml; 0.60 mV; 0.49 meqN ⁺ / (min × L cells); 52.0 sec The obtained values were substituted into the formula for calculating the concentration of free hemoglobin in the blood after surgery:

Y = 139.60-1.43 · 18.5-0.44 · 3.51-29.20 · 0.60-38.64 · 0.49-0.90 · 52 = 28.4 mg / dl .

The level of postperfusion hemoglobinemia predicted before surgery was correct; in a patient after IR, the concentration of free hemoglobin in blood plasma was 26.5 mg / dl, which was only 7% different from the predicted value (28.4 mg / dl). This level of hemoglobinemia was regarded as insignificant, since it does not exceed the threshold of clinically significant hemolysis (40 mg / dl), which, thanks to the developed formula, was determined before the operation and after it was associated with a short hospital stay (16 days), lack of protein in the urine its entire length and a small volume of pleural exudate after surgery (150 ml on the 2nd day after surgery). Meanwhile, according to the existing traditional approach in predicting the severity of hemolysis after surgery based on an analysis of the conditions for its implementation, somewhat increased (exceeding the average statistical level) duration of IR and hematocrit during perfusion suggested the development of significant hemolysis after surgery, which nevertheless less, did not form, obviously, due to the high hemolytic resistance of red blood cells due to their preoperative structural and metabolic status m

Example 2. Patient N., 59 years old. Diagnosis: ischemic heart disease. Angina pectoris III functional class, postinfarction cardiosclerosis (2010), circulatory failure II NYHA functional class, duration of coronary heart disease 4 years. Concomitant diseases: hypertension of the 2nd degree, chronic gastritis (remission), pneumofibrosis, gallstone disease. The duration of cardiopulmonary bypass was 108 min, the average perfusion: temperature 36.12 ° C, the volumetric perfusion rate of 5.6 l / min, the intensity of the coronary suction 543 ml / min, blood oxygenation level of 168 mm Hg, hematocrit 22, 7%; there was no intraoperative transfusion of erythromass; red blood diseases were not observed in the last 6 months before surgery.

A study according to the proposed method. In the blood taken before surgery, the concentration of EPO and TNF-α, the parameters of Ca ²⁺ -induced GPO of erythrocytes ΔE, V ₂ and ΔT were respectively: 8.08 mIU / ml; 2.85 pg / ml; 0.56 mV; 0.64 meqN ⁺ / (min × L cells); 33.8 s The obtained values were substituted into the formula for calculating the concentration of free hemoglobin in the blood after surgery:

Y = 139.60-1.43.8.08-0.44 2.85-29.20 0.56-38.64 0.64-0.90 33.8 = 55.2 mg / dl.

Forecast: High probability of hemolytic complications in the postoperative period.

The level of postperfusion hemoglobinemia predicted before surgery was correct; in a patient after IR, the plasma concentration of free hemoglobin was 56.1 mg / dl, which was only 2% different from the predicted value (55.2 mg / dl). This level of hemoglobinemia was regarded as high, since it exceeded the threshold of clinically significant hemolysis (40 mg / dl), which was calculated before the operation and after that was associated with a long hospital stay (20 days), the presence of protein in the urine (0.34 g / l, 4 days after surgery) and a large volume of pleural exudate after surgery (450 ml, 3 days after surgery). Meanwhile, according to the existing traditional approach in predicting the severity of hemolysis after surgery based on an analysis of the conditions for its implementation, slightly increased (exceeding the average statistical level) indicators of blood oxygenation and volumetric perfusion rate testified in favor of the development of significant hemolysis after surgery, and low hematocrit and the intensity of the coronary pump with an average duration of IR, on the contrary, allowed to suggest the development of ety hemoglobinemia. Thus, the prognosis of hemolysis based on the conditions of the operation was uncertain, while the application of the proposed method made it possible to obtain a quantitative indicator, which made it possible to accurately predict the formation of clinically significant hemolysis.

Thus, the application of the proposed method, which predicts the degree of hemolytic complications in patients with coronary heart disease after surgery with cardiopulmonary bypass, and its introduction into the clinical practice of cardiac surgery departments will allow predicting the magnitude of postperfusion hemoglobinemia and the development of highly probable hemolytic complications even at the preoperative stage, which will allow the cardiologist and cardiac surgeon to prescribe preparations for the primary prevention of hemolysis, and to the perfusiologist and anesthetist-resuscitator scorre ted tactics perfuziologicheskogo software and choose the optimal method of secondary prevention of severe hemoglobinemia. In General, the result of the application of the method will be expressed in improving the quality of life of patients in the early postoperative period, reducing the cost of health resources for their postoperative rehabilitation and reducing the mortality of cardiac patients from hemolysis-induced complications.

Information sources

1. Standardization of the assessment of intraoperative hemolysis during cardiac surgery in conditions of cardiopulmonary bypass / I.I. Dementieva, Yu.A. Morozov, M.A. Charnaya et al. // Cardiology and cardiovascular surgery. - 2010. - No. 4. - S. 75-78.

2. Vercamest, L. Hemolysis in cardiac surgery patients undergoing cardiopulmonary bypass: A review in search of a treatment algorithm / L. Vercamest // The J. of Extra Corporeal Technology. - 2008 - Vol.40, N4. - P.257-267.

3. Patent RU No. 23037353, publ. 09/27/2007 "A method for determining the dynamic characteristics of red blood cells."

4. US patent No.2011300574, publ. 08/12/2011 "Cell-couting method for blood hemolysis analysis in fragility measurements.

5. Patent RU No. 2179315, publ. 02/10/2002 “A method for determining the functional state of an organism by the degree of blood resistance to acid hemolysis”

6. Dogra, N. Glucose-6-phosphate dehydrogenase deficiency and cardiac surgery / N. Dogra, G. D. Puri, S.S. Rana // Perfusion. - Vol.25, N6. - P. 417-421.

7. Maltseva, I.V. The characteristic of erythrocyte resistance in cardiosurgical patients with varying degrees of severity of postperfusion hemolysis / I.V. Maltseva // Bulletin of Siberian medicine. - 2013. - T.12, No. 1. - S.69-74.

application

Table 1

Clinical characteristics of the studied groups of patients with coronary heart disease before coronary artery bypass surgery in conditions of cardiopulmonary bypass

Note. Hereinafter in Table 2: coronary heart disease - coronary heart disease, NYHA (New York Heart Association) - New York Heart Association, duodenum - duodenum.

table 2

Characterization of the perfusion stage of coronary artery bypass surgery in patients with coronary heart disease $$\left(\overline{X}\pm m\right)$$

Note: See table 1, pO ₂ - partial pressure of oxygen in the blood, HbO ₂ - degree of saturation of hemoglobin with oxygen, Hct - hematocrit.

Table 3

Results of a regression analysis between clinical and laboratory parameters before surgery and the level of postperfusion hemoglobinemia in patients with coronary heart disease

Note: R is the coefficient of multiple correlation, R ² is the coefficient of determination, p is the level of statistical significance of the obtained formula, X _IR is the duration of cardiopulmonary bypass, X _pO2 is the maximum partial pressure of oxygen in the blood during surgery. Parameters of the preoperative period: X _Er - content of red blood cells, X _Ret - content of reticulocytes in blood, X _Fb - content of fibrinogen in blood plasma, X _{XC / PL} - ratio of cholesterol and phospholipid in the erythrocyte membrane, X _IR - index of rigidity of red blood cells, X _{Na / K} is the activity of Na ⁺ / K ⁺ adenosine triphosphatase of the erythrocyte membrane, X _Cat is the activity of catalase in erythrocytes, X _IF is the proportion of inositol phosphate in the erythrocyte membrane, X _PS is the proportion of phosphatidylserine in the erythrocyte membrane, X _PEA is the proportion of erythrocyte nitrate X _FC - share phos atidnoy acids in the erythrocyte membrane, X _EPO - the concentration of erythropoietin in blood plasma before surgery, X _TNF - concentration of tumor necrosis factor α in blood plasma, X _hapten - haptoglobin concentration in the blood plasma, X _GfV - percentage of glycophorin B ⁺ red blood cells, X _ΔE - amplitude of Ca ²⁺ -induced hyperpolarizing response erythrocytes, X _V2 - regeneration membrane potential at Ca ²⁺ -induced hyperpolarizing response erythrocytes, X _ΔT - time of the maximum value of the membrane potential at Ca ²⁺ -indutsirov nnom hyperpolarizing response to red blood cells

Table 4

Calculated according to the multiple regression equation and the actual values of the concentration of free hemoglobin in the blood in patients with coronary heart disease after cardiopulmonary bypass

Table 1 Indicator IHD patients Number of patients: 90 men,% 85.56 women,% 14.44 Age years 59.40 ± 1.03 Duration of coronary heart disease, years 5.16 ± 0.97 Functional class of angina pectoris II,% 18.89 III,% 74.44 IV,% 6.67 Functional class of circulatory failure (NYHA) I,% 8.89 II,% 78.89 III,% 12.22 Hypertension of the III degree,% 91.11 Type 2 diabetes mellitus,% 14.44 Thyroid Dysfunction,% 8.89 Prostate dysfunction,% 15,55 Gastrointestinal tract pathology: - peptic ulcer of the stomach and / or duodenum,% 17.77 - gastritis,% 70.00 Diseases of the liver and biliary tract,% 32.22 Urinary system diseases,% 36.66 Lung diseases,% 17.77 Perioperative risk by Euroscor,% 2.43 ± 0.31

table 2 Indicator IHD patients The duration of cardiopulmonary bypass, min 112.09 ± 3.84 Duration of myocardial ischemia, min 75.48 ± 6.11 Volume perfusion rate average, l / min 5.22 ± 0.08 Maximum perfusion volumetric rate, l / min 5.38 ± 0.10 pO ₂ average, mmHg 150.13 ± 5.63 pO ₂ maximum, mmHg 195.72 ± 6.92 HbO ₂ average,% 98.52 ± 0.33 HbO ₂ minimum,% 97.08 ± 0.67 Hct average,% 24.60 ± 0.95 Hct minimum,% 23.00 ± 0.74 Perfusion temperature average, ° C 36.09 ± 0.26 Minimum perfusion temperature, ° C 35.52 ± 0.19 The intensity of the coronary suction, ml / min 670.34 ± 48.17 The proportion of patients with a different number of shunted arteries,% 2 arteries 15,56 3 arteries 43.33 4 arteries 36.67 5 arteries 4.44 The concentration of free hemoglobin in the blood 1 h after surgery, mg / dl 34.27 ± 7.28

Table 3 No. Multiple Linear Regression Equation R R ² p one Y = -7.57 + 0.20 · X _IR + 0.13 · X _pO2 0.44 0.20 0.04 2 Y = 42.09-1.23; X _Er -0.36; X _Ret + 5.82; X _Fb 0.36 0.13 0.77 3 Y = 222,73-145,31 · X _XC / _{FL -1,30 · X Ret + 0,27 · X} IR 0.87 0.76 0.18 four Y = -344.61 + 456.81 · X _{Na / K} -5.34 · X _Cat + 16.52 · X _IF + 7.42 · X _FS + 5.06 · X _PEA + 5.18 · X _FC 0.96 0.93 0.19 5 Y = 36.96 + 1.09 · X _EPO -1.70 · X _TNF + 0.08 · X _Hapt -0.37 · X _GfV 0.61 0.38 0.37 6 Y = 139.60-1.43 · X _EPO -0.44 · X _TNF -29.20 · X _ΔE -38.64 · X _V2 -0.90 · X _ΔT 0.98 0.96 0.02

Table 4 The concentration of free hemoglobin in blood plasma after surgery, mg / DL Patient Code 23 24 26 29th thirty 31 32 35 36 Actual value 13.5 28.0 26.5 45.9 56.1 51.0 49.8 63,2 33.0 Estimated value 12.5 33.0 28,4 41.1 55,2 52.7 46.1 65.0 32.9

Claims (1)

A method for predicting the degree of risk of developing hemolytic complications after coronary artery bypass surgery in cardiopulmonary bypass by evaluating the state of the peripheral erythron unit before surgery, characterized in that the content of hematopoietins in the blood before surgery is estimated, for which the amplitude, time of its development and rate of restoration of the membrane potential at Ca ²⁺ -induced hyperpolarizing response erythrocytes (GAP), the concentration of erythropoietin (EPO) and tumor necrosis factor-α (TNF-α) in rovi, and in the case of belonging to their respective confidence intervals: the amplitude of from 0.11 to 1.01 mV; the time of its development from 26.16 to 60.12 s, GPO from 0.49 to 0.91 meqN + / (min × l cells); EPO from 2.94 to 20.14 mIU / ml and TNF-α from 0.21 to 6.8 pg / ml, respectively, calculate the concentration of free hemoglobin in the blood after surgery Y according to the formula:

where 139.60 is a constant for patients with coronary heart disease with a risk of developing severe hemoglobinemia;
1.43; 0.44; 29.20; 38.64 and 0.90 - numerical values are coefficients;
X _EPO - concentration of EPO in plasma (mIU / ml);
X _TNF - concentration of TNF-α in blood plasma (PG / ml);
X _ΔE is the amplitude of Ca ²⁺ -induced GPO of erythrocytes (mV);
X _V2 — rate of restoration of membrane potential in Ca ²⁺ -induced HPO of erythrocytes (meqH + / (min × l cells));
X _ΔT is the development time of the maximum value (amplitude) of the membrane potential with Ca ²⁺ -induced HPO of red blood cells (seconds),
and with Y exceeding 40 mg / dl, a high degree of risk of developing hemolytic complications in the postoperative period is predicted.