RU97922U1 - SYSTEM FOR LIPID HEMODIALYSIS - Google Patents

Abstract

 A system for lipid hemodialysis, including a dialysis machine, blood lines for perfusion through a dialyzer, characterized in that the dialysis machine is equipped with a scale and a lipid-containing dialysis solution connected to the lines with a peristaltic pump and dialyzer, with adapters installed in front of the dialyzer (fittings) for tubes of different diameters.

Description

The proposed utility model relates to medicine, namely to replacement and intensive care, toxicology, and can be used to ensure the removal of fat-soluble substances from the blood by means of lipid hemodialysis.

The problem of removing fat-soluble (associated with lipids and lipoproteins) toxic substances (dichloroethane, carbon tetrachloride, benzene, etc.), drugs (propranolol, digoxin, diazepam, etc.), as well as fat-soluble metabolites that become high in concentration toxic, lead to damage to the functions of various organs, tissues or important regulatory mechanisms (bile acids, prostacyclins, nitric oxide, indole and phenolic metabolites, thiols, etc.) is still far from resolving Eden.

Efferent therapy is one of the areas actively used in intensive care (Sussman N.L., 1998; Santoro A. et al., 2004). Dialysis is a process of exchange of molecules between two solutions through semipermeable membranes. Substances dissolved in blood and dialysis fluid diffuse through the dialysis membrane, and the difference in the concentration of the substance in the blood and dialysate is the driving force behind diffusion (Daugirdas D.T. et al., 2003). If the concentration of a substance in the blood is greater than in the dialysate, the substance diffuses into the dialysis fluid (for example, urea, creatinine, phosphate, potassium, etc.). Conversely, if the concentration of the substance in the dialysate is greater than in the blood, the substance enters the blood (for example, bicarbonate, which is in the dialysate to correct acidosis). The category of particles that can be exchanged is determined by the size and architectonics of the pores in the semipermeable membrane and the molecular weight of the particles. However, fat soluble substances, i.e. “Connected” with plasma lipids and lipoproteins are not transported into the dialysis fluid because it does not contain lipids that they can contact. The same effect is observed for substances associated with proteins, they are not eliminated in a normal dialysis solution that does not contain protein. For the elimination of substances associated with blood plasma proteins, special systems have been developed, for example, molecular adsorption-recirculation system (MARS)

The molecular adsorption-recirculation system (MARS), combining the effects of plasma filtration, plasma sorption on ion-exchange resins and synthetic activated carbons and albumin-mediated hemodialysis, ensures the deligandization of patient albumin and transmembrane mass transfer of plasma metabolites associated with plasma proteins (Kym . al., 1999; Stange J. et al., 1999).

Systems for elimination through a semipermeable membrane of fat-soluble substances have not been previously developed.

An analogue of a utility model is a system for hemodialysis (Stetsyuk EA, Lebedev SV Classical hemodialysis. Moscow, 1997. - P.22-29). It includes an artificial kidney apparatus, dialyzer, blood lines, dialysis fluid lines, and dialysis fluid concentrate. A concentrate is a saline solution that is prepared in the factory and comes ready-made in cans or hermetically sealed bags that contain the exact amount of all the ingredients. Dialysis solutions used for hemodialysis on "artificial kidney" apparatuses are obtained by mixing proportional pump of a dialysis dialysis machine with dialysis fluid (34: 1 ratio) and buffering the mixture through a bicarbonate cartridge.

The flow direction of the dialysis fluid through the dialyzer is opposite to the direction of the blood flow, which increases the concentration gradient in all parts of the dialyzer.

The advantages of the analogue are the ability to remove water-soluble substances from blood plasma and the correction of plasma electrolytes by direct and reverse transport through the dialyzer membrane.

The disadvantage of the analogue is the impossibility of eliminating fat-soluble and / or protein-related substances, since the dialysis fluid used in this procedure does not contain lipids or proteins that would allow ligand substances to bind to lipid or, respectively, protein molecules of the dialysis fluid. Existing models of hemodialysis machines are designed to work with concentrated salt solutions, which are diluted with a proportional pump of dialysis machines in a ratio of 1:34, and the hydraulic system requires constant sterilization, which cannot be performed after filling it with protein-containing or lipid-containing solutions.

The closest analogue to the utility model is the molecular adsorption-recirculation system (MARS), capable of removing substances associated with plasma proteins (Mitzner SR, Stange J., Klammt S. et al. Improvement of hepatorenal syndrome with extracorporeal albumin dialysis MARS: Results of a prospective , randomized, controlled clinical trial. Liver Transplantation. - 2000. - Vol.6. - No. 3. P.277-286). The MARS system includes an artificial kidney apparatus, a Teraclin molecular adsorption-recirculation system apparatus (Germany), and standard consumables: MARS-flux hemodiafilter, diaMARS IE 250 cation exchange resin, diaMARS AC 250 carbon sorbent, low-flux diaFLUX dialyzer. The primary dialysis solution in contact with the patient’s blood through a semipermeable membrane is 20% human donor albumin, which is recycled by a MARS peristaltic pump. The circulating albumin, in turn, is purified from the ligands bound to it by perfusion through activated carbon and a cation exchange resin included in the albumin circuit, and then it is further purified from trapped water-soluble substances in the third circuit, where albumin itself is dialyzed in countercurrent with a standard dialysis cell. bicarbonate solution through the diaFLUX dialyzer membrane. Thus, an albumin-containing dialysis solution is able to remove hydrophobic toxins and metabolites associated with albumin from the patient’s blood.

The most significant drawback is the inability to use the MARS system to eliminate fat-soluble metabolites, xenobiotics, poisons, which makes it impossible to use it to treat a wide range of pathological conditions. Other disadvantages are the use of two types of dialysis solution - standard bicarbonate solution and albumin-containing and the high cost of consumables for the procedure.

Research Objective:

- providing technical feasibility of the lipid hemodialysis procedure, i.e. hemodialysis using dialysis fluid containing lipids in high (over 10%) concentration.

The essence of the utility model is a system for lipid hemodialysis, including a dialysis machine, blood lines for perfusion through a dialyzer, characterized in that the dialysis machine is equipped with a scale and a lipid-containing dialysis solution connected to the peristaltic pump and the dialyzer by highways, and in front of the dialyzer at the inlet / outlet pipes have adapters (fittings) for tubes of different diameters.

The technical result of using the system is to ensure the implementation of lipid hemodialysis procedures, i.e. hemodialysis using dialysis fluid containing lipids in high (over 10%) concentration. This allows you to increase the effectiveness of treatment, reduce the time of medical and social rehabilitation, improve the quality of life of the patient.

The system for lipid hemodialysis, to improve understanding, is shown in figure 1., where p. - a dialysis machine (an artificial kidney apparatus, 2 - a dialyzer, 3 - a peristaltic pump, 4 - blood lines, 5 - a container with a lipid-containing dialysis raster, 6 - scales, 7 - adapters, 8 - dialysis fluid line

The lipid hemodialysis system is used as follows:

The dialysis machine 1 is prepared for the hemodialysis procedure according to the instructions for its use until the testing stage. Universal blood lines 4 are connected to a high-flow dialyzer 2 and installed in the clamps of the dialysis apparatus, the perfusion segment of the arterial blood line is installed in the peristaltic blood pump 3 of the dialysis machine 1. A physiological solution of sodium chloride is used to fill the blood lines 4 and dialyzer 2.

Dialysis fluid line connectors are left in the flushing port clamps. Another set of connectors complete with silicone dialysis fluid lines and another set of blood lines are used to make the lines of 8 lipid dialyzed solution. The silicone tubes put on the connectors are cut off, leaving a length of 5-7 cm; open a set of universal blood lines, cut off the dialyzer connectors on the “arterial” and “venous” blood lines and, using adapters 7 (fittings), connect segments of silicone and blood lines with different diameters of the exits.

Dialysis fluid connectors snap into the dialysate fluid outlets of dialyzer 2 so that the arterial line (having a peristaltic pump segment) is installed on the same side as the blood inlet.

Adapters 7 of the two dialysis fluid lines made for connecting to the fistula needle are connected to the connectors of the bag in which the substitute is replaced with a lipid-containing dialysis fluid 5. The segment of the “arterial” line with the lipid-containing dialysis fluid is fixed in the grooves of the additional peristaltic pump 3 mounted on the dialysis cap cars. On the rod of the hemodialysis apparatus, scales 6 of the “steelyard” type are suspended and a container with a lipid-containing dialysis fluid 5 is suspended on their hook, with down connectors and its weight is recorded to account for the increase / loss with ultrafiltration.

Blood lines 4 are connected to the "arterial" and "venous", respectively, the entrance and exit of a double-lumen dialysis catheter.

After the introduction of a bolus dose of heparin, the peristaltic pump 3 of the dialysis machine 1 is turned on, the perfusion rate is adjusted to the required value. Turn on the peristaltic pump 3 with a segment of the line dialysis fluid 8 and bring the speed of perfusion to the necessary. A lipid hemodialysis procedure is performed. To change the bag with a lipid-containing dialysis fluid, both peristaltic pumps are stopped, the bag is replaced, and the procedure is continued.

Example 1

A dialysis machine 4008S (Fresenius, Germany) was prepared for the hemodialysis procedure according to the instructions for its use prior to the testing phase. Universal blood lines were connected to a high-flow dialyzer F70S (Fresenius, Germany) and installed in the clamps of the dialysis apparatus. The perfusion segment of the "arterial" blood line was installed in a peristaltic blood pump of the dialysis machine. A 0.9% sodium chloride solution was used to fill the blood lines and the dialyzer.

The connectors of the dialysis fluid lines (Cat. No. 3451445A, Fresenius, Germany) were left in the terminals of the washing port of the 4008S dialysis machine (Fresenius, Germany). Another set of the same connectors complete with silicone dialysis fluid lines (Cat. No. 39236315, Frezenius, Germany) and another set of blood lines were used to make the lines of the lipid-containing dialysis solution. The silicone tubes worn on the connectors were cut off, leaving a length of 5-7 cm; They opened a set of universal blood lines, cut off the dialyzer connectors on the “arterial” and “venous” blood lines, and, using fittings with different output diameters, connected a piece of the silicone line and the blood line.

Dialysing fluid connectors snapped onto the dialyser dialysis fluid outlets so that the arterial line (having a peristaltic pump segment) was installed on the same side as the blood inlet.

Adapters of both dialysis fluid lines made to connect to the fistula needle were connected to the connectors of the bag in which the substitute was replaced with a lipid-containing dialysis fluid. As a dialysis solution, a container with a lipid-containing dialysis liquid obtained by diffusion and convection through the dialysis membrane of a 20% offsinal emulsified solution of essential lipids — Lipofundin MCT / LST in countercurrent with a standard dialysis solution for 2 hours (patent application No. 2010105593) was used 02.16.2010 g)

A segment of the arterial line with a lipid-containing dialysis fluid was fixed in the grooves of an additional peristaltic pump mounted on the lid of the dialysis machine. An “steelyard” type balance was mounted on the rod of the hemodialysis apparatus and a container with a lipid-containing dialysis fluid was hung on its hook with the connectors down and its weight was recorded to account for increase / loss with ultrafiltration.

Blood lines were connected to the “arterial” and “venous”, respectively, the entrance and exit of the double-lumen dialysis catheter.

After administering a bolus dose of heparin, the peristaltic pump of the dialysis machine was turned on and the perfusion rate was adjusted to 100-150 ml / min. A peristaltic pump was switched on with a dialysis fluid line segment and its perfusion rate was adjusted to the required value. To change the bag with a lipid-containing dialysis fluid, both peristaltic pumps were stopped, the bag was replaced, and the lipid hemodialysis procedure was continued.

Example 2

A series of bench tests (5 procedures) of the use of lipid hemodialysis using lipid-containing dialysis fluid was carried out (patent application No. 2010015593 dated 02.16.2010). Assembled a system for lipid hemodialysis (see example No. 1). Cyclosporin was added to a bag containing canned donated blood. “Cyclosporin is practically not excreted during hemodialysis” (Instructions for use of the drug Cyclosporin (Sandimmun Neoral, manufacturer Novartis Pharma AG (Switzerland)), since it is a fat-soluble substance.

The drug was administered in a dose that creates highly toxic concentrations in donated blood of about 3000 ng / ml, which is 20-15 times higher than the usual blood concentrations of patients receiving the drug for immunosuppressive therapy. After thorough mixing, 5 ml of blood with cyclosporin dissolved in it was taken into a separate tube.

A lipid hemodialysis procedure was performed for 4 hours. The change of the package with lipid-containing dialysis fluid was performed 2 hours after the start of the procedure. Blood samples were taken from the port of the “arterial” line to the dialyzer before starting, after 30 minutes and then every hour of the procedure. Conducted a study of laboratory parameters of blood and the concentration of cyclosporine in it (table 1).

Table 1 Blood parameters containing highly toxic doses of cyclosporine during lipid hemodialysis options Before the procedure 30 minutes 1 hour 2 hours 3 hour 4 hour Cyclosporin, ng / ml 3764 ± 102 1392 ± 93 1118 ± 89 968 ± 91 390 ± 64 274 ± 73 Red blood cells, x10 ¹² / l 4.24 ± 0.32 4.24 ± 0.65 4.34 ± 0.55 4.43 ± 0.55 4.44 ± 0.79 4.51 ± 0.67 Hemoglobin, g / l 132.08 ± 8.93 135.86 ± 18.92 133.57 ± 16.8 135.14 ± 15.16 138.14 ± 15.12 141.06 ± 12.62 Hematocrit% 0.40 ± 0.03 0.41 ± 0.06 0.40 ± 0.04 0.40 ± 0.04 0.41 ± 0.07 0.42 ± 0.05 Free hemoglobin, g / l 2.57 ± 1.13 2.68 ± 1.18 2.87 ± 1.42 2.96 ± 1.22 3.16 ± 1.74 3.32 ± 1.67 Osmolarity, mosm / l 316.43 ± 11.18 299.29 ± 10.64 295.86 ± 6.91 295.57 ± 7.74 295.14 ± 7.71 294.21 ± 8.51 Cholesterol, mmol / L 3.96 ± 1.33 4.09 ± 0.84 4.01 ± 1.12 4.11 ± 1.12 4.14 ± 1.07 4.17 ± 1.26 Triglycerides, mmol / L 0.92 ± 0.24 1.38 ± 0.15 1.39 ± 0.15 1.41 ± 0.17 1.44 ± 0.18 1.48 ± 0.28 pH 7.06 ± 0.11 7.31 ± 0.15 7.33 ± 0.15 7.37 ± 0.1 7.32 ± 0.11 7.34 ± 0.14 Potassium, mmol / L 10.31 ± 2.21 6.40 ± 2.29 5.21 ± 2.23 5.02 ± 2.15 5.15 ± 2.13 5.03 ± 2.21 Sodium, mmol / L 156.14 ± 13.67 149.37 ± 11.49 143.33 ± 12.14 144.2 ± 12.17 143.3 ± 12.84 142.9 ± 10.57 Ionized calcium, mmol / l 0.06 ± 0.02 0.31 ± 0.04 0.36 ± 0.04 0.46 ± 0.05 0.60 ± 0.04 0.73 ± 0.06 Chlorides, mmol / L 92.00 ± 6.22 96.71 ± 2.56 98.14 ± 2.48 98.07 ± 2.71 98.71 ± 2.63 99.22 ± 2.94

At the same time, a study was conducted on the content of blood cyclosporin in a test tube that did not undergo lipid hemodialysis (Table 2).

table 2 The concentration of cyclosporine in blood not subjected to lipid hemodialysis. options Before the procedure 30 minutes 1 hour 2 hours 3 hour 4 hour Cyclosporin, ng / ml 3764 ± 102 3820 ± 107 3790 ± 96 3772 ± 81 3742 ± 111 3736 ± 98

As follows from table 1, as a result of the use of lipid hemodialysis, the concentration of cyclosporin in the blood decreased already by the first hour after the start of the lipid hemodialysis procedure, whereas in the test tube (table 2) there was no decrease in its concentration over time. Extremely positive changes in pH, osmolarity and electrolytes were revealed. Concentrations of triglycerides, cholesterol, free hemoglobin remained within physiological values (table 1).

Thus, a series of bench tests of the use of lipid hemodialysis using a lipid-containing dialysis fluid showed a decrease in the concentration of a fat-soluble substance, cyclosporine, in the blood.

Claims (1)

A system for lipid hemodialysis, including a dialysis machine, blood lines for perfusion through a dialyzer, characterized in that the dialysis machine is equipped with a scale and a lipid-containing dialysis solution connected to the lines with a peristaltic pump and dialyzer, with adapters installed in front of the dialyzer (fittings) for tubes of different diameters.