Background. Innovative advances in cardiac surgery to reduce the negative impact of cardiopulmonary bypass (CPB) require a comprehensive solution. The ultimate questions of present interest remain the prevention of hypoxia, the composition of the priming volume of the oxygenator, the state of erythrocytes and their energy potential, the level of hemolysis, the pathogenetic approach to the correction of electrolytes during perfusion, as well as the biocompatibility of the extracorporeal circuit. The study aimed to create the protocol for cardiopulmonary bypass, which includes the possibility of reducing the negative effects of synthetic polymers of the extracorporeal circuit; reducing the hydrodynamic load on the tissue; carrying out a more physiological correction of the acid-base state; improving the energy potential of cells; correction of electrolyte balance during cardiopulmonary bypass taking into account the stages of the surgical operation. Materials and methods. The study included 225 patients who underwent cardiac surgery using cardiopulmonary bypass. The patients were divided into three groups. The first group consisted of 75 people, whose extracorporeal contour was treated with the adaptive composition by a special technique. After centrifuging the patient’s blood, serum was obtained, which was diluted in a solution of 0.9% NaCl and treated with the oxygenator circuit. The second group included patients (n = 75) in whom fructose-1,6-diphosphate (FPD) was used in the perfusion regimen. The drug was administered intravenously at a dose of 10 g at a rate of 10 ml/min in two stages: 5 g of FPD were injected immediately before the start of perfusion and 5 g before the patient was warmed up. The third group was the control group. Perfusion was performed using a membrane oxygenator in a non-pulsating blood flow mode with a prime of 1.3–1.6 L to achieve moderate hemodilution (Ht — 25 ± 2 g/L). A hyperosmolar priming volume with a total osmolarity of up to 510.6 mmol/L was used. The basic solutions were volutens, reosorbilact, mannitol 15%, Soda-buffer 4.2%. Hemogram (Hb, Ht, MCV, MCH, MCHC, RDWa, RDW%, hemolysis), oxygen transport: saturation of arterial (SaO2%) and venous blood (SvO2%), partial pressure of oxygen in arterial (PaO2) and venous blood (PvO2), oxygen delivery index (IDO2), oxygen consumption index (IVO2), oxygen extraction (O2ER), and oxygen extraction index (O2EI) were studied. The research of morphological changes in erythrocytes was carried out. Results. Our study aimed to develop and implement into practice an optimized cardiopulmonary bypass protocol based on the results obtained. The previous studies have shown that treatment of the oxy-genator circuit with the adaptive composition creates a protective layer of autoalbumin on the inner surface of the extracorporeal circuit, and the use of a drug with the active fructose-1,6-diphosphate ingredient during perfusion allows correcting hypophosphatemia, reducing the energy deficiency of the cells. In these two groups, in comparison with the control one, after CPB, there was a lower level of hemolysis, a lower number of echinocytes, and spherocytes. The three groups used the hyperosmolar priming volume. Before perfusion, there were the following indices: IDO2 — 332.00 ± ± 84.84 ml/(min • m2), IVO2 — 76.07 ± 28.34 ml/(min • m2), O2ЕR — 22.91 ± 6.33 %, O2EI — 22.47 ± 6.32 %, BE = –0.78 ± 2.13 mmol/L. At 10 min after CPB, there were the following indices: IDO2 — 579.7 ± 112.3 ml/(min • m2), IVO2 — 30.91 ± 13.31 ml / (min • m2), O2ER — 5.35 ± 2.07 %, O2EI — 5.26 ± ± 2.08 %, BE = 0.82 ± 2.03 mmol/L. IDO2 increased due to the oxygenator gas exchange, and the decrease in IVO2, O2ЕR, O2EI can be explained by the patient’s cooling. At the warming stage, there were the indices: IDO2 — 598.8 ± 114.9 ml/(min • m2), IVO2 — 108.10 ± 33.11 ml/(min • m2), O2ER — 18.04 ± 4.14 %, O2EI — 17.95 ± 4.15 %, BE = –0.11 ± 8.88 mmol/L. IDO2 — 305.7 ± 60.9 ml / min • m2), IVO2 — 77.15 ± 24.29 ml/(min • m2), O2ЕR — 25.36 ± 6.5 %, O2EI — 25.34 ± 6.5 %, BE = –0.36 ± 2.20 mmol/L. After CPB, the rate of diuresis was 11.88 ± 5.31 ml/kg/h, the relative hydrobalance after CPB was 9.67 ± 8.12 ml/kg. Our proposed protocol for cardiopulmonary bypass includes the basic points: 1) treatment of the oxygenator contour with the adaptive composition; 2) in patients with an initially low level of phosphorus, administration of the drug of fructose-1,6-diphosphate by the scheme; 3) the use of a hyperosmolar priming volume of the oxygenator; 4) correction of electrolytes taking into account the stages of cardiac surgery. Conclusions. The proposed procedure for the treatment of the extracorporeal oxygenator circuit is simple and affordable, improves the biocompatibility of the oxygenator. The use of a hyperosmolar priming volume avoids the volume load and provides an adequate gas transport function of the blood. The application of FPD makes it possible to reduce hemolysis and protect erythrocytes, correct electrolytes by taking into account the stages of operations and the peculiarities of CPB.