Sources for obtaining whole human blood and its components are not unlimited and currently cannot meet the needs of surgery, especially if we take into account the increasing number of surgical interventions using artificial blood circulation machines, which require large amounts of blood. Obtaining and using cadaveric blood and drugs from waste blood also did not completely solve this problem.
Advances in chemistry and enzymology have made it possible to create heteroprotein, polysaccharide and synthetic drugs from available raw materials.
Blood replacement fluid is a physically homogeneous transfusion medium with a targeted effect on the body, capable of replacing a certain blood function.
Mixtures of various blood-substituting fluids or their sequential use can have a complex effect on the body.
Blood replacement fluids must meet the following requirements:
1) be similar in physical and chemical properties with blood plasma;
2) completely excreted from the body or metabolized by enzyme systems;
3) do not cause sensitization of the body with repeated administrations;
4) not to provide toxic effect on organs and tissues;
5) withstand sterilization for long term maintain their physicochemical and biological properties.
Blood-substituting fluids are usually divided into colloidal solutions- dextrans (dextran [average molecular weight 50,000-70,000], dextran [average molecular weight 30,000-40,000]), gelatin preparations; saline solutions- isotonic sodium chloride solution, Ringer-Locke solution; buffer solutions- sodium bicarbonate solution, trometamol solution; solutions of sugars and polyhydric alcohols(dextrose, sorbitol, fructose); protein preparations(protein hydrolysates, amino acid solutions); fat preparations- fat emulsions (for example, Soybean oil + Triglycerides); hydroxyethyl starch preparations(hydroxyethyl starch).
Classification of blood-substituting fluids (depending on the direction of action)
I. Hemodynamic (anti-shock).
1. Low molecular weight dextrans - dextran [cf. they say weight 30,000-40,000], Dextran [cf. molecular weight 30,000-50,000] + Mannitol + Sodium chloride.
2. Medium molecular dextrans - dextran [cf. they say weight 50,000-
70 000].
3. Gelatin preparations.
4. Preparations based on hydroxyethyl starch - hydroxyethyl starch.
II. Detoxification. Low molecular weight polyvinyl alcohol.
III. Preparations for parenteral nutrition.
1. Protein hydrolysates - Amino acids + Peptides, Amino acids + Dextrose + Mineral salts + Peptides.
2. Amino acid solutions - polyamine.
3. Fat emulsions - Soybean oil + Triglycerides.
4. Sugars and polyhydric alcohols - dextrose, sorbitol, fructose.
IV. Regulators of water-salt and acid-base status.
1. Saline solutions- isotonic sodium chloride solution, Ringer's solution.
2. Buffer solutions - sodium bicarbonate solution, trometamol solution.
V. Oxygen carriers- perftoran, perfucal.
BLOOD SUBSTITUTE FLUIDS WITH HEMODYNAMIC (ANTI-SHOCK) ACTION
Medium-molecular blood substitutes are mainly hemodilutants; they help increase blood volume and thereby restore blood pressure levels. They are able to circulate in the bloodstream for a long time and attract intercellular fluid into the vessels. These properties are used for shock and blood loss. Low-molecular blood substitutes improve capillary perfusion, circulate in the blood for less time, and are excreted more quickly by the kidneys, carrying away excess fluid. These properties are used in the treatment of capillary perfusion disorders, to dehydrate the body and combat intoxication by removing toxins through the kidneys.
Dextran[cf. they say weight 50,000-70,000] - colloidal solution of dextran (dextrose polymer of bacterial origin). It contains a medium molecular weight (60,000×10,000) fraction of dextran, the molecular weight of which is close to that of albumin, which ensures normal colloid osmotic pressure in human blood. The drug is a 6% solution of dextran in an isotonic sodium chloride solution, pH = 4.5-6.5. Available in sterile form in 400 ml bottles. Stored at temperatures from -10?C to +20?C. Shelf life: 5 years. The drug may freeze; after thawing, the medicinal properties are restored.
The mechanism of the therapeutic action of dextran [cf. they say weight 50,000-70,000] is due to its ability to increase and maintain bcc by attracting fluid from the interstitial spaces into the vascular bed and retaining it due to its colloidal properties (hemodilution). When using dextran [cf. they say weight 50,000-70,000] the increase in blood plasma volume exceeds the volume of the administered drug. The drug circulates in the vascular bed for 3-4 days, its half-life is 1 day.
According to the hemodynamic effect of dextran [cf. they say weight 50,000-70,000] is superior to all known blood substitutes; due to its colloid-osmotic properties, it normalizes blood pressure and central venous pressure and improves blood circulation. In dextran [cf. they say weight 50,000-70,000] there are up to 20% low molecular weight fractions of dextran, which can increase diuresis and remove toxins from the body. Dextran [cf. they say weight 50,000-70,000] promotes the release of tissue toxins into the vascular bed and then their removal by the kidneys. Indications for use are the following: 1) shock (traumatic, burn, surgical); 2) acute blood loss; 3) acute circulatory failure in severe intoxication (peritonitis, sepsis, intestinal obstruction, etc.); 4) exchange blood transfusions for hemodynamic disorders.
Use of the drug not shown with skull trauma and increased intracranial pressure, ongoing internal bleeding.
A single dose of the drug is 400-1200 ml, if necessary it can be increased to 2000 ml. Dextran [cf. they say weight 50,000-70,000] is administered intravenously by drip and stream (depending on the patient’s condition). In emergency situations, a jet infusion is started, and when blood pressure rises, they switch to a drip infusion at a rate of 60-70 drops per minute.
Dextran[cf. they say weight 30,000-40,000] - 10% solution of low molecular weight (molecular weight 35,000) dextran in an isotonic solution of sodium chloride. Capable of increasing BCC, every 20 ml dis-
The solution is mixed with an additional 10-15 ml of water from the interstitial fluid. The drug has a powerful disaggregating effect on red blood cells, helps eliminate blood stasis, reduce its viscosity and increase blood flow, i.e. improves the rheological properties of blood and microcirculation. It has a strong diuretic effect, so it is advisable to use it for intoxication. Dextran [cf. they say mass 30,000-40,000] leaves the vascular bed within 2-3 days, but the main amount is excreted in the urine in the first day. Indications The requirements for using the drug are the same as for other hemodynamic blood substitutes; in addition, it is used for the prevention and treatment of thromboembolic disease, for post-transfusion complications, and for the prevention of acute renal failure. The dose of the drug is 500-750 ml. Contraindication for its use are chronic kidney diseases.
Gelatin- 8% solution of partially hydrolyzed gelatin in an isotonic sodium chloride solution. Relative molecular weight 20,000?5000. Due to its colloidal properties, the drug increases the bcc. They mainly use the rheological properties of gelatinol, its ability to thin the blood (reduce viscosity) and improve microcirculation. Has no nutritional value. After 2 hours in bloodstream Only 20% of the drug remains and is completely excreted within 1 day in the urine. It is administered by drip and stream intravenously, intra-arterially, the drug is used to fill the heart-lung machine. The maximum dose for 1 administration is 2000 ml. Relative contraindications for its use are acute and chronic nephritis.
Transfusion therapy in emergency situations (shock, acute blood loss, acute vascular insufficiency), you should start with drugs that can quickly restore blood volume. The use of donor blood leads to a loss of 20-30 minutes (the time required to determine blood groups, compatibility tests, etc.). In terms of its ability to restore bcc, donor blood has no advantages over colloidal plasma substitutes. In addition, with shock and severe deficiency of bcc, a disruption of capillary blood flow occurs, the causes of which are an increase in blood viscosity, aggregation of formed elements and microthrombosis. This microcirculation disorder is aggravated by transfusion of donor blood. In this regard, transfusion therapy in case of shock and even blood loss should be started with intravenous administration of anti-shock blood substitutes - dextran [cf. they say weight 50,000-70,000] and dextran [cf. they say weight 30,000-40,000].
BLOOD SUBSTITUTE FLUIDS
DISINTOXIFICATION ACTION
3% solution of low molecular weight polyvinyl alcohol in isotonic sodium chloride solution. Available in bottles with a capacity of 100, 200 and 400 ml. Store at a temperature not lower than +10? C. Single dose - 250 ml. The drug is administered twice with an interval of several hours, the rate of administration is 20-40 drops per minute. Indications Severe purulent-inflammatory diseases accompanied by purulent-resorptive fever, purulent peritonitis, intestinal obstruction, sepsis, burn disease, postoperative and post-traumatic conditions are recommended for use. Contraindications for the use of the drug are thrombophlebitis, thromboembolic condition (due to the danger of embolism).
PREPARATIONS FOR PARENTERAL NUTRITION
Protein hydrolysates
Protein hydrolysates are used to replenish the nutritional function of the blood. The preparations are solutions of protein hydrolysis products (hydrolysates) and contain essential and essential amino acids and low molecular weight peptides. The latter undergo final breakdown in the liver during transfusion. Amino acids + Peptides are obtained from technical casein. Amino acids + Dextrose + Mineral salts + Peptides are prepared from whole donor blood not used for transfusion, red blood cells and blood clots remaining after plasma collection, as well as waste (placental) blood. A whole protein molecule is not subject to breakdown in the liver, therefore whole blood, plasma, and serum cannot be considered a nutrient medium and they can only be used for hemocorrection. If the complex of transfused amino acids does not contain at least one essential amino acid, protein synthesis does not occur.
Amino acids + Peptides contains 43-59 g of amino acids and simple peptides, 5.5 g of sodium chloride, 0.4 g of potassium chloride, 0.4 g of calcium chloride, 0.005 g of magnesium chloride per 1000 ml of pyrogen-free water. Available in bottles of 200 and 400 ml. Stored at temperatures from 10 to 23? C. Shelf life: 7 years. The drug is well absorbed by the body (nitrogen absorption reaches 80-93%), does not have anaphylactogenic
properties. During storage, a slight sediment may form, which disappears when the bottle is shaken.
Amino acids + Dextrose + Mineral salts + Peptides contains nonessential and essential amino acids and simple peptides; their quantitative composition is close to other hydrolysates. A 5% dextrose solution was added to the solution. Available in 400 ml bottles. Stored at a temperature of 4-20? C. Shelf life: 3 years. When storing the drug, a small sediment may appear, which easily disperses when the bottle is shaken. The presence of persistent sediment and turbidity serves as an indicator that the drug is unsuitable for use.
Amino acid mixtures
Amino acid mixtures are balanced mixtures of crystalline amino acids in optimal ratios for absorption. The preparations contain all essential and especially valuable non-essential amino acids. The following preparations are solutions of amino acids: polyamine, aminofusin, moriamin, vamin.
Polyamine- a preparation containing 8 essential amino acids and D-sorbitol. The content of total nitrogen is 1.13%, tryptophan - 145 mg in 100 ml of pyrogen-free water. Available in bottles of 200 and 400 ml. Stored at temperatures from -10 to +20? C. Shelf life: 2 years.
Dose of protein blood replacement solutions at complete parenteral nutrition is determined by the body’s daily need for protein (1-1.5 g/kg) and is 1500-2000 ml/day for protein hydrolysates, 800-1200 ml/day for amino acid mixtures, and 700-1000 and 400 for partial parenteral nutrition, respectively. -600 ml/day (half dose). Combinations of protein blood replacement solutions, amino acid solutions, blood products (plasma, albumin solution) are used taking into account the body’s total daily need for protein and its content in transfusion media.
Indications for the use of protein blood replacement solutions and amino acid mixtures. Protein hydrolysates are used to prepare patients for surgery.
Various pathological conditions (oncological diseases, purulent-inflammatory processes, diseases accompanied by a violation of natural nutrition - gastric ulcer, stenosis of the esophagus, antrum, etc.) are accompanied by disturbances in protein metabolism, which leads to hypo- and dysproteinemia. This affects the body’s resistance to surgical trauma,
infections, leads to impaired wound healing after surgery and the development of complications. The use of protein hydrolysates and amino acid mixtures makes it possible to correct dys- and hypoproteinemia. The use of protein blood replacement solutions after operations, especially on the esophagus, stomach, and intestines, allows one to maintain a normal nitrogen balance in the body and ensures a more favorable course of the postoperative period.
The use of protein hydrolysates is indicated for purulent-inflammatory diseases (peritonitis, pleural empyema, lung abscess, extensive phlegmon, osteomyelitis) and intestinal obstruction, which are always accompanied by significant breakdown of protein and its loss with exudate, pus, and intestinal contents.
Of great importance is the use of protein blood-substituting fluids for burn disease, which is accompanied by large losses of protein due to burn injury and subsequent plasma loss, as well as in the case of purulent-inflammatory complications.
Contraindications for the use of protein blood-substituting fluids are acute circulatory disorders (shock, blood loss), acute and subacute renal failure, thrombosis, thrombophlebitis, thromboembolism.
Protein hydrolysates and amino acid mixtures are administered intravenously, very rarely - subcutaneously, and also through a probe inserted into the small intestine during surgery on the stomach and esophagus.
Fat emulsions
Soybean Oil + Triglycerides - 20% soybean oil emulsion with particle size less than 1 micron, energy capacity 2100 kcal/l. Fat emulsions are especially indicated for long-term parenteral nutrition (for 3-4 weeks). It is advisable to use them in cases where it is necessary to add a large amount of calories in a limited volume of liquid.
Contraindications For infusions of fat emulsions, shock, the early postoperative period, severe liver diseases, fat embolism, thrombophlebitis, thromboembolism, severe atherosclerosis, uncompensated diabetes mellitus, and lipid metabolism disorders are used.
Sugars, polyhydric alcohols
To cover the body's energy needs during parenteral nutrition, dextrose, fructose, and sorbitol are used. Very
plays a big role dextrose, which is used in the form of 5%, 10%, 20% and 40% solutions. She is able to support energy metabolism. Excess dextrose is quickly eliminated by the kidneys, so it is rarely used on its own, but is used as an energy supplement to other blood replacement fluids, especially protein hydrolysates. If the body's absorption of glucose is impaired (diabetes mellitus, stress, shock), fructose and sorbitol are used. Fructose almost completely metabolized in the liver, its absorption does not depend on insulin. Used as a 5%, 10% or 20% solution.
Sorbitol- polyhydric alcohol, which is absorbed by splitting in the liver. Its absorption does not depend on insulin, so it can be used for parenteral nutrition of patients diabetes mellitus. Used as a 5% solution.
The sugars used contribute to the accumulation of proteins in the body; their dose for parenteral nutrition is 250 g/day.
ELECTROLYTE SOLUTIONS
Balanced transfusion therapy involves the introduction of electrolyte solutions to restore and maintain osmotic pressure in the interstitial space. Electrolyte solutions improve the rheological properties of blood and restore microcirculation. In case of shock, blood loss, severe intoxication, or dehydration of the patient, water transfers from the intercellular spaces into the bloodstream, which contributes to fluid deficiency in the interstitial space. Saline solutions with low molecular weight easily penetrate through the capillary wall into the interstitial space and restore fluid volume. All saline blood-substituting fluids quickly leave the bloodstream. To increase the period of circulation in the blood, it is advisable to use them together with colloidal solutions.
Isotonic sodium chloride solution is a 0.9% aqueous solution of sodium chloride. Available in sealed bottles or prepared in a pharmacy. If there is significant loss of fluid by the body, accompanied by extracellular dehydration, up to 2 liters of the drug can be administered per day. It quickly leaves the bloodstream, so its effectiveness in shock and blood loss is negligible. Used in combination with blood transfusions, blood-substituting solutions with anti-shock action.
Ringer-Locke solution. Composition of the drug: sodium chloride 9 g, sodium bicarbonate 0.2 g, calcium chloride 0.2 g, potassium chloride 0.2 g, dextrose 1 g, bidistilled water up to 1000 ml. The solution is more physiological in composition than an isotonic sodium chloride solution. It is used to treat shock, as well as to replenish blood loss in combination with transfusions of blood, plasma, and hemodynamic blood-substituting fluids.
As acid-base regulators, a 5-7% solution of sodium bicarbonate and a 3.66% solution are used trometamol.
Oxygen carriers. This group includes perfluorocarbon derivatives (peftoran, perfucol) and soluble hemoglobin preparations. They are called "artificial blood". They have the property of reversibly binding oxygen. Issues related to their clinical use have not been fully clarified: their pharmacokinetics have not been sufficiently studied, and the drugs are not without toxicity.
PRINCIPLES OF PARENTERAL NUTRITION
In severe conditions of the body caused by shock, blood loss, surgery and disruption of natural food intake, transfusion therapy is necessary, which, along with replenishing the deficit of bcc and restoring the water-electrolyte balance, provides the body with energy and plastic materials, which increase significantly under stressful conditions. Due to the lack of plastic materials, the reparative abilities of tissues are reduced, which is especially important in postoperative period. The lack of energy materials leads to the consumption of tissue proteins and plastic materials introduced in the form of hydrolysates and amino acids. All this determines the need for balanced parenteral nutrition, taking into account the needs of the body. The minimum daily energy requirement of the body is 25 kcal, protein - 1-1.5 g/kg, fat - 1-2 g/kg.
The energy capabilities of blood substitutes for parenteral nutrition are as follows: 1 g of dextrose provides 4 calories, 1 liter of a 20% dextrose solution provides 800 calories, 1 g of lipids provides 9 calories. Alcohol can be used as an energy source: 1 g of alcohol gives 7 calories, no more than 50-100 ml of alcohol is administered per day, added to other transfusion media in 5-7% concentration. Rational parenteral nutrition includes solutions of crystalloids, sodium bicarbonate (or trometamol), dex-
trans and vitamins, taking into account the water-electrolyte and acid-base state of the body. Protein in hydrolysates contains about 5%, in plasma and serum - 7.5-9%.
Fat emulsions are used to cover the body's energy needs. The use of an isotonic dextrose solution for this purpose involves the need to administer large volumes of liquid, and highly concentrated solutions are dangerous due to the development of plasma hyperosmolarity. At the same time, using only fat emulsions as an energy source entails the appearance of ketone bodies in the body. Therefore, parenteral nutrition combines fat emulsions and carbohydrates.
The use of native proteins in the form of whole blood, plasma, protein, albumin is inappropriate for parenteral nutrition, since the half-life of proteins in the body is 14-30 days. Therefore, protein-containing blood components are used to urgently replace plasma volume deficiency. The proteins introduced with them circulate in the bloodstream for a long time and perform corresponding functions.
With parenteral nutrition, the total volume of transfusion per day is 2500-3000 ml (1500 ml per 1 m 2 of body surface plus 500 ml for every degree increase in body temperature). The total calorie content of the solutions should correspond to the amount of fluid administered (in milliliters). An approximate scheme of parenteral nutrition, taking into account the energy and plastic needs of the body, may be as follows.
1. 20% dextrose solution - 500 ml, 70% ethanol solution - 50 ml, protein hydrolysates (or amino acid solution) - 500 ml, Ringer-Locke solution - 500 ml, vitamins C, B 1, B 2. Administered intravenously over 4-5 hours in the first half of the day. According to indications, the transfusion composition is supplemented with solutions of sodium bicarbonate, trometamol, and potassium chloride.
2. 20% dextrose solution - 500 ml, Soybean oil + Triglycerides - 500 ml, protein hydrolysates (or amino acid solution) - 500 ml, 20% solution of albumin, protein or plasma - 50-100 ml. Administered intravenously over 4-5 hours in the second half of the day. Vitamins are administered taking into account the daily needs of the body. According to indications, solutions of electrolytes, etc. are added. To increase the absorption of proteins, anabolic hormones (nandrolone) are used.
MAIN STEPS AND SEQUENCE OF ACTIONS OF THE DOCTOR WHEN TRANSFUSING BLOOD SUBSTITUTE FLUIDS
Determining indications for transfusion
Assessment of the patient's condition allows us to identify the need for transfusion of hemodynamic (anti-shock) blood replacement fluids, which are indicated for various types of shock, acute blood loss, and dextran [cf. they say weight 30,000-40,000], in addition, for microcirculation disorders associated with thrombophlebitis, thromboembolism, and vascular operations. In case of purulent intoxication, traumatic toxicosis, transfusions of blood substitutes with detoxifying action are performed. Full or partial parenteral nutrition is prescribed if enteral nutrition is impossible or limited - in case of hypoproteinemia, diseases accompanied by significant protein breakdown (purulent diseases, burns). In case of dehydration, electrolyte imbalance, or acid-base status, transfusion of electrolyte solutions, sodium bicarbonate, and trometamol is indicated.
Identifying contraindications for transfusion
It is necessary to find out whether the patient has acute liver failure, cardiac decompensation, thrombosis, or embolism. It is important to collect a transfusion and allergy history, i.e. information about the patient’s tolerance to blood-substituting fluids in the past, to determine the presence of allergic diseases. Protein blood replacement fluids are contraindicated in cases of decompensated liver failure, acute glomerulonephritis, allergic diseases, and active pulmonary tuberculosis.
Choosing the route of administration of blood substitutes
The main route of drug administration is intravenous, with the exception of subcutaneous administration. Protein hydrolysates are also administered through a probe passed transnasally into the intestine after surgery on the esophagus or stomach. To ensure the transfusion of blood substitute fluids, the following equipment is required: 1) a transfusion system (one-time use) with a dropper; 2) needle for venipuncture; 3) short and long needles for the bottle in the case of using a reusable system; 4) sterile tray; 5) rubber band; 6) alcohol
for treating the injection site and the rubber cap of the bottle; 7) sterile gauze balls; 8) stand for ampoule; 9) Mohr-type clamp to regulate the speed of drip administration of the drug; 10) Billroth clamp; 11) adhesive plaster.
Determination of combinations of blood substitutes
The determination of combinations of blood substitutes is determined by the indications for transfusion therapy: traumatic shock, purulent intoxication, burn shock, acute blood loss, prolonged fasting in the postoperative period, protein deficiency, water-salt imbalance, changes in blood pH (acidosis), preparation for surgery in exhausted patients with disorders digestion.
Determining the suitability of hematopoietic fluids
The shelf life of the drug, possible violations of the storage conditions specified in the instructions (overheating or freezing of solutions), and damage to the integrity of the bottle should be taken into account. Signs of unsuitability include cloudiness of the solution, the presence of flakes, films on the surface, and sediment. The presence of a small sediment is allowed only in Amino Acids + Peptides.
Transfusion technique
Installation of the infusion system is carried out in the same way as for blood transfusion. The disposable system is filled with a solution so that there are no air bubbles in it and a dropper can be used to count drops. After processing surgical field and puncture the vein with a needle, 20-25 ml of a 0.5% procaine solution is injected through it with a syringe, then a system for drip administration of blood-substituting solutions is connected to the needle. A single dose for subcutaneous administration should not exceed 500 ml. Subcutaneous administration of the drug is used extremely rarely, since this method is less effective: protein digestibility is much lower, and in case of shock the effect of a rapid increase in blood volume is not achieved.
Carrying out a biological test
A biological test is necessary when transfusing protein hydrolysates, fat emulsions, and dextran [cf. they say weight 50,000-
70,000]. The biological test involves intermittent infusion of 5, 10 and 15 ml of the drug with an interval of 3 minutes. If there is no reaction (anxiety, tachycardia, difficulty breathing, facial flushing, skin itching, rash, drop in blood pressure), the transfusion can be continued.
When transfusion of fat emulsions, an extended biological test is carried out: during the first 10 minutes, the drug is administered at a rate of 10-20 drops per minute; if there are no reactions, the administration is continued at a rate of 20-30 drops per minute.
With dextran transfusion [cf. they say weight 50,000-70,000] after infusion of the first 10 ml and the next 30 ml, take a break for 3 minutes; if there is no reaction, the transfusion is continued.
Determination of the rate of drug administration
In emergency situations, they begin jet injection of blood-substituting fluids with anti-shock action, and then switch to drip injections - 60-70 drops per minute. Blood-substituting detoxifying fluids and electrolyte solutions are administered at a rate of 40-50 drops per minute. When protein preparations are administered at a rate of 20 drops per minute, 85% of amine nitrogen is assimilated by the liver, no pyrogenic or toxic reactions are observed; at a speed of 40-60 drops per minute, 73% of nitrogen is absorbed, in some cases complications are observed; at a rate of 100 drops per minute, 22% of nitrogen is absorbed, complications are often observed. It is most advisable to administer protein hydrolysates and amino acid solutions at a rate of 20-40 drops per minute.
Monitoring the patient's condition
It is necessary to monitor the patient’s well-being, behavior, appearance, color skin, determine pulse and breathing rates. When the first signs of transfusion reactions appear (for example, anxiety, headache, facial flushing, skin rash, tachycardia, increased breathing), the infusion is slowed down or stopped. If the reaction does not go away on its own, appropriate medications are administered.
Registration of transfusion
At the end of the infusion, an appropriate entry is made in the medical history and the register of transfusions of blood substitute fluids, noting the amount and type of drugs administered, and the presence of a reaction.
Adverse reactions to the administration of blood replacement solutions are rare. Thus, when using protein hydrolysates and fat emulsions, they are observed in 1-1.5% of cases, with the infusion of dextran [cf. they say weight 50,000-70,000] - 0.1% as a manifestation of individual hypersensitivity to the drug.
There are allergic, pyrogenic, toxic reactions. Allergic reactions administration of protein hydrolysates is possible in patients with severe purulent processes, burns due to autosensitization and in persons suffering from allergic diseases. Manifest in the form of cyanosis, suffocation, tachycardia, swelling of the eyelids, face (Quincke's edema), skin itching and rash. Pyrogenic reactions consist of an increase in body temperature, the appearance of chills at the end of the transfusion of blood substitutes or after it. To prevent a reaction, it is necessary to use disposable systems, change the system during long-term (more than 1 day) infusion, and use drugs taking into account their shelf life. Toxic reactions are expressed in headache, tachycardia, liver enlargement, lower back pain, and changes in urine. The reason for this is the increased content of protein breakdown products in the protein hydrolyzate. Transfusion of blood replacement fluids with signs of unsuitability or expired storage is strictly prohibited.
If complications occur during the infusion of blood replacement fluids, you should immediately stop the transfusion or slow down the rate of drug administration, inject intravenously 10 ml of a 10% calcium chloride solution, antihistamines (diphenhydramine, chloropyramine), 20 ml of a 40% dextrose solution, 1 ml 0.2 % platiphylline solution, 1 ml of 1% trimeperedine solution. When blood pressure drops, vasoconstrictors and cardiac drugs, crystalloid solutions, and glucocorticoids are used.
To prevent complications, it is necessary to follow the rules of transfusion, find out the transfusiological and allergological history, not exceed the daily dose and rate of administration of protein drugs (20-40 drops per minute), be sure to conduct a biological test when transfusing protein blood substitutes, dextran [cf. they say weight 50,000-70,000] and fat emulsions. If a reaction to the drug is suspected, promethazine, chloropyramine or diphenhydramine and calcium chloride are first administered (10-15 minutes before).
Blood-substituting fluids (blood substitutes, plasma-substituting solutions) are solutions for parenteral administration (subcutaneous, intramuscular, intravenous), used to replenish the volume of fluid circulating in the bloodstream, remove toxic substances from the body, as well as for the purpose of parenteral nutrition (for example, if it is impossible eating after a burn, surgery, etc.). The administration of blood replacement fluids is possible without taking into account the patient’s blood group. Most of them do not have a sensitizing (see) effect and do not cause anaphylactoid reactions. According to the classification of the Leningrad Institute of Blood Transfusion (LIBK), all blood substitute fluids are divided into the following groups: 1) saline crystalloid solutions; 2) blood-substituting fluids with components of human blood; 3) colloidal blood-substituting fluids with colloids foreign to the human body - from heterogeneous protein, blood-substituting fluids with colloids of plant origin and synthetic colloidal solutions; 4) anti-shock solutions that have a special therapeutic purpose; 5) protein hydrolysates.
Saline crystalloid solutions (Ringer's, Ringer-Locke's solutions, LIPC No. 3, saline infusin TsOLIPK, etc.) have a low molecular weight compared to protein and colloid solutions and are quickly cleared from the bloodstream. They are indicated for administration when it is necessary to immediately replenish fluid in the body - in case of dehydration, as well as in case of acute blood loss (especially complex saline blood replacement fluids, for example, saline infusin TsOLIPK), in case of intoxication, etc. (see Isotonic solutions).
Blood-substituting fluids with components of human blood - serotransfusin CIPC, albumin solutions, dry plasma solutions - have a high molecular weight and are slowly removed from the bloodstream, providing good support arterial pressure. They are indicated for use in cases of shock, blood loss, burns, as well as in the treatment of pathological processes accompanied by dehydration of the body. When they are administered, pathological reactions usually do not develop.
Blood-substituting fluids with colloids foreign to the human body - BK-8, Belenky's therapeutic (LSB), etc. - are similar in their mechanism of action to blood-substituting fluids with components of human blood and are used for the same indications. However, some of them may cause phenomena (increased sensitivity of the body) when administered repeatedly. Therefore, a reactivity test is necessary before infusion (see below). Of the blood-substituting fluids in this group, the most widely used are synthetic colloidal solutions - polyglucin, polyvinylpyrrolidone, polyvinol and hemodez.
Polyglucin is a 6% colloidal solution (in isotonic sodium chloride solution) of a high molecular weight compound - glucose. Due to its large molecular weight, close to the molecular weight of blood albumin, polyglucin, when introduced into the bloodstream, circulates in it for a long time: 40% of the administered drug is retained in the blood during the day. It has the most pronounced anti-shock effect. Up to 2000 ml is administered intravenously and intraarterially. In case of large blood losses and extensive burns, infusions begin with polyglucin, since it raises blood pressure faster than blood, and then move on to or plasma.
Polyvinylpyrrolidone is a polymer compound; A 3.5% solution of polyvinylpyrrolidone is called hemovinyl. In terms of anti-shock properties, hemovinyl is inferior to polyglucin, but superior to saline blood replacement fluids.
Polyvinol is a 2.5% colloidal solution of a polymer compound, its effect is close to solutions of polyvinylpyrrolidone. Used for blood loss and shock intravenously and intra-arterially up to 1 liter. tachycardia, difficulty breathing).
Blood replacement solutions. Hemodynamic blood substitutes, detoxification solutions, blood substitutes for parenteral nutrition, regulators water-salt metabolism and acid-base status, oxygen carriers, infusion antihypoxants.
Hemodynamic drugs (anti-shock blood substitutes) are intended to normalize central and peripheral hemodynamics, which are impaired due to blood loss, mechanical trauma, burn shock, various diseases internal organs(perforated gastric and duodenal ulcers, intestinal obstruction, acute cholecystitis, acute pancreatitis, exogenous and endogenous intoxications).
Solutions of this group have a high molecular weight and pronounced colloid-osmotic properties, due to which they circulate for a long time in the vascular bed and attract intercellular fluid into it, significantly increasing the bcc (volemic effect). In addition to the main effect, hemodynamic blood substitutes also have a detoxification effect, improve microcirculation and rheological properties of blood.
Antishock blood substitutes include four groups of drugs:
Dextran derivatives
Gelatin preparations,
Hydroxyethyl starch derivatives,
Derivatives of polyethylene glycol.
Dextran derivatives
Depending on the molecular weight, solutions are distinguished:
Medium-molecular (polyglucin, polyfer, rondex, macrodex, intradex, dextran, plasmodex, chemodex, oncovertin);
Low molecular weight (reopolyglucin, reogluman, rheomacrodex, lomodex, dextran-40, hemodex).
The main medium molecular weight drug of dextran is polyglucin, and the low molecular weight drug is rheopolyglucin.
Poliglyukin - 6% solution of the medium molecular weight fraction of dextran (molecular weight 60,000 - 80,000) in isotonic sodium chloride solution. When administered intravenously, it quickly increases blood volume, increases and persistently maintains blood pressure. Polyglucin increases the volume of circulating fluid in the bloodstream by an amount exceeding the volume of the administered drug, which is explained by its high colloid osmotic pressure. It circulates in the body from 3 to 7 days, on the first day 45-55% of the drug is excreted, the predominant route of elimination is through the kidneys. The introduction of polyglucin enhances redox processes in the body and the utilization of oxygen from the inflowing blood by tissues. Injection of the drug increases vascular tone.
Polyglucin is indicated in the treatment of traumatic, surgical and burn shock: acute blood loss, acute circulatory failure in various diseases. Adverse reactions with the administration of polyglucin are extremely rare. However, in some individuals (less than 0.001%) there is an individual increased sensitivity to the drug, manifested in the development of symptoms of anaphylaxis up to anaphylactic shock. To prevent this reaction when using polyglucin, it is necessary to conduct a biological test.
Reopoliglyukin - 10% solution of low molecular weight dextran (molecular weight 20,000-40,000) in an isotonic sodium chloride solution or 5% glucose solution. Like polyglucin, it is a hyperoncotic colloid solution and, when administered intravenously, significantly increases the volume of blood volume. Each gram of the drug binds 20-25 ml of water in the bloodstream. This explains its hemodynamic effect. Reopolyglucin circulates in the body for 2-3 days, 70% of the drug is excreted in the urine in the first day.
The main effect of rheopolyglucin, in contrast to polyglucin, is the improvement of the rheological properties of blood and microcirculation. This is due to the drug’s ability to cause disaggregation of red blood cells, relieve blood stasis and prevent thrombus formation. The high concentration of the drug that occurs in the blood promotes the flow of fluid from the tissues into the bloodstream, which leads to hemodilution and a decrease in blood viscosity. Dextran molecules cover the surface of blood cellular elements and change the electrochemical properties of red blood cells and platelets. The antithrombotic effect of rheopolyglucin is probably due to an increase negative charge platelets and a decrease in their ability to adhesion and aggregation. Indications for the use of rheopolyglucin are microcirculation disorders during shocks of various origins, thromboembolic complications, open heart surgery, vascular diseases, surgical interventions on blood vessels, post-transfusion complications, prevention of acute renal failure.
Reactions and complications when using rheopolyglucin are the same as when using polyglucin. Before administration, it is also necessary to conduct a biological test.
Gelatin preparations.
Gelatin preparations include gelatinol, modelel, hemogel, gelofusin, plasmogel. The founder of the group and the most common drug is gelatinol.
Gelatinol is an 8% solution of partially digested edible gelatin in an isotonic solution of sodium chloride (molecular weight 15,000-25,000). Gelatinol is a protein that contains a number of amino acids: glycine, proline, etc. The therapeutic effect is mainly associated with its high colloid-osmotic pressure, which ensures the rapid flow of tissue fluid into the vascular bed. As hemodynamic drugs, gelatinol and its analogues are less effective than dextrans. They leave the vascular bed faster and are distributed in the extracellular space. Gelatinol is non-toxic, pyrogen-free, and antigenic reactions are not typical. The main part of the drug is excreted by the kidneys.
Indications for use are acute hypovolemia, different kinds shock and intoxication. The drug is contraindicated in acute diseases kidneys and fat embolism.
Due to possible allergic reactions when using gelatinol, a biological test is required.
Hydroxyethyl starch derivatives.
The first generation of hydroxyethyl starch solutions was created from potato starch, but the drugs were not approved for clinical use. Second generation of solutions (HAES-steril, plasmosteril, hemohes, refortan, stabizol) made from corn starch. Domestic drugs in this group include Volecam and Oxyamal.
The most widespreadHAES-sterilized iplasmosteril . The structure of the drugs is close to glycogen in animal tissues and can be destroyed in the bloodstream by amylolytic enzymes. Solutions based on hydroxyethyl starch have a good hemodynamic effect, side effects are rare.
When using hydroxyethyl starch derivatives, the concentration of serum amylase may increase on days 3-5. In rare cases, drugs can cause anaphylactoid reactions, so it is advisable to conduct a biological test.
Derivatives of polyethylene glycol.
This group of blood substitutes includes polyoxidine, which is a 1.5% solution of polyethylene glycol in a 0.9% sodium chloride solution. Molecular weight - 20,000. In terms of its hemodynamic and volumetric characteristics, it is similar to drugs from the hydroxyethyl starch group. In addition, it improves the rheological properties of blood and reduces tissue hypoxia. It is excreted mainly by the kidneys. The half-life is about 17 hours, circulates in the blood for up to 5 days. Has virtually no side effects.
Detoxification solutions.
Detoxifying blood substitutes are designed to bind toxins circulating in the blood and remove them from the body in the urine. They are effective only if the toxins are able to form complexes with the drug, as well as while maintaining the excretory function of the kidneys and the ability of the “blood substitute - toxin” complex to be filtered in the renal glomeruli. When using these drugs, the load on the kidneys sharply increases, so patients with impaired renal function, and especially with acute renal failure, are not prescribed drugs from this group.
The main drugs are derivatives of polyvinylpyrrolidone (gemodez, neogemodez, periston-N, neocompensan, plasmodan, kolidon) and a solution of low molecular weight polyvinyl alcohol - polydez.
Hemodez - 6% solution of low molecular weight polyvinylpyrrolidone with a molecular weight of 12,000-27,000. Most of it is excreted by the kidneys 6-8 hours after intravenous administration. Active against many toxins, with the exception of diphtheria and tetanus, as well as toxins formed during radiation sickness. It also eliminates stasis of red blood cells in capillaries during acute blood loss, shock, burn disease and others. pathological processes. Depending on the degree of intoxication, adults are administered intravenously from 200 to 400 ml per day, and children at the rate of 15 ml / kg of body weight. Contraindication for use is bronchial asthma, acute nephritis, cerebral hemorrhage.
Neohemodesis - 6% solution of low molecular weight polyvinylpyrrolidone with a molecular weight of 6000-10,000 with the addition of sodium, potassium and calcium ions. The detoxification effect of neohemodez is higher than that of hemodez.
Indications for use are similar to those for hemodez. In addition, the therapeutic effect of neohemodesis is clearly manifested in thyrotoxicosis, radiation sickness, various liver diseases and other pathologies. The drug is administered intravenously at a rate of 20-40 drops per minute, maximum single dose for adults it is 400 ml, for children 5-10 ml/kg.
Polidez - 3% solution of polyvinyl alcohol in isotonic sodium chloride solution. Molecular weight 10,000-12,000. Completely excreted by the kidneys within 24 hours. Polydesis is used intravenously to treat intoxication caused by peritonitis, intestinal obstruction, acute pancreatitis, acute cholecystitis, acute purulent infection, burn disease, liver damage, etc. Adults are prescribed 200-500 ml per day, children at the rate of 5-10 ml/kg. With rapid administration of the drug, dizziness and nausea may occur.
Blood substitutes for parenteral nutrition.
Parenteral nutrition preparations are indicated in case of complete or partial exclusion of the patient’s natural nutrition due to certain diseases and after surgical interventions on organs gastrointestinal tract; for purulent-septic diseases; traumatic; radial and thermal injuries; severe complications of the postoperative period (peritonitis, abscesses and intestinal fistulas), as well as hypoproteinemia of any origin. Parenteral nutrition is provided by protein preparations, fat emulsions and carbohydrates. The former contribute to the intake of amino acids into the body, and fat emulsions and carbohydrates supply it with energy for the absorption of protein.
Along with proteins, carbohydrates and fats, electrolytes play an important role in parenteral nutrition: potassium, sodium, calcium, phosphorus, iron, magnesium, chlorine, as well as microelements: manganese, cobalt, zinc, molybdenum, fluorine, iodine, nickel, etc. The first take part in the most important metabolic and physiological processes, are part of the structure of cells, including blood cells, are necessary for the regulation of osmotic processes, etc. The latter regulate the functional activity of enzymes, hormones, etc. To enhance the effect of parenteral nutrition, additionally vitamins and anabolic hormones are prescribed.
Protein preparations
Protein preparations include protein hydrolysates and mixtures of amino acids.
The sources of protein hydrolysates are casein, cattle blood proteins, muscle proteins, as well as red blood cells and donor blood clots. When obtaining protein hydrolysates, the starting material is subjected to enzymatic or acid hydrolysis. The most widely used are casein hydrolysate, hydrolysin, aminokrovin, amikin, aminopeptide, fibrinosol, aminosol, aminon, amigeni, etc.
Protein hydrolysates are administered intravenously at a rate of 10-30 drops per minute.
The volume of introduced hydrolysates can reach 1.5- 2 l per day. Contraindications to the use of protein hydrolysates are acute hemodynamic disorders (shock, massive blood loss), cardiac decompensation, cerebral hemorrhage, renal and liver failure, thromboembolic complications.
Protein hydrolysates can be administered through a tube into the stomach (tube feeding).
A separate group consists of solutions of amino acids, which are easily absorbed by the body, since there is no need to break down peptides. The advantage of mixtures of crystalline amino acids is a simpler production technology, a high concentration of amino acids, the ability to create drugs with any ratio of amino acids and the addition of electrolytes, vitamins and energy compounds to the mixture. Main drugs: polyamine, infusamine, vamin, moriamin, freemin, alvezin, aminoplasmal etc. Amino acid mixtures are administered intravenously at 20-30 drops per minute with total parenteral nutrition at a dose of 800-1200 ml daily. They can be administered through a tube into the stomach.
When transfusing any protein drugs, a biological test must be performed.
Fat emulsions.
Inclusion of fat emulsions in parenteral nutrition complex \ improves the energy of the patient’s body, has a pronounced nitrogen-saving effect, corrects the lipid composition of the plasma and the structure of cell membranes. Fats provide the body with essential fatty acids (linolenic, linoleic, arachidonic), fat-soluble vitamins (A, K, D), and phospholipids. IN clinical practice use fat emulsions (emulsified fats do not cause fat embolism). The most widely used are intralipid, lipiphysian, infuzolipol, lipofundin, lipomul, infonutrol, fatgen and others.
Fat emulsion preparations are administered intravenously at a rate of 10-20 drops per minute or through a tube into the stomach.
The use of fat emulsions is contraindicated in cases of shock, traumatic brain injury, liver dysfunction, and severe atherosclerosis. Before performing the infusion, a biological test is prescribed.
Carbohydrates.
Carbohydrates are used in parenteral nutrition to meet energy needs, and also as an energy supplement to protein hydrolysates. Carbohydrates introduced into the body contribute to the breakdown of protein hydrolysates and the construction of their own proteins from amino acids.
The most common solutions are glucose solutions (5%, 10%, 20% and 40%). A contraindication to its use is diabetes.
Other carbohydrates include fructose and carbohydrate alcohols (xylitol, sorbitol, mannitol). The absorption of these drugs is not directly related to the action of insulin and is possible in patients with diabetes mellitus.
Regulators of water-salt metabolism and acid-base status.
Drugs in this group include crystalloid solutions and osmotic diuretics.
Crystalloid solutions
All crystalloid solutions can be divided into two groups.
1. Solutions that correspond in their electrolyte composition, pH and osmolarity to blood plasma - the so-called basic crystalloid solutions. The main drugs are Ringer's solution, Ringer-Locke solution, lactosol.
In clinical practice, these solutions are used to correct isotonic hydroionic disorders, since they contain the most optimal set of ions.
2. Solutions that differ in electrolyte composition, pH and osmolarity from blood plasma - the so-called corrective solutions, which are intended to correct violations of the hydroionic and acid-base balance.
This group of drugs includes: physiological (isotonic) sodium chloride solution (0.9% solution), Acesol, Chlosol, Disol, Trisol, sodium bicarbonate solution 4-5% sodium bicarbonate (soda) solution is used to correct metabolic acidosis.
Crystalloid solutions have a low molecular weight and quickly penetrate through the capillary wall into the intercellular space, restoring fluid deficiency in the interstitium. They leave the vascular bed quite quickly. In this regard, the combined use of crystalloid and colloid solutions is advisable.
Crystalloids, along with hemodynamic colloid blood substitutes, include complex therapy traumatic and hemorrhagic shock, purulent-septic diseases, and is also used for the prevention and correction of disturbances in the water-salt balance and acid-base balance of the blood during major operations and in the postoperative period. In this case, not only the deficiency of extracellular fluid is replenished, metabolic acidosis is compensated and detoxification occurs, but also some hemodynamic effect occurs, consisting in the partial correction of hypovolemia and stabilization of blood pressure.
Osmodiuretics
Osmodiuretics include polyhydric alcohols: mannitol and sorbitol.
Mannitol- 15% solution of mannitol in isotonic sodium chloride solution.
Sorbitol -20% solution of sorbitol in isotonic sodium chloride solution.
The mechanism of the diuretic action of these drugs is associated with an increase in plasma osmolarity and the influx of interstitial fluid into the bloodstream, which contributes to an increase in blood volume and an increase in renal blood flow.
As a result of increased renal filtration, the excretion of sodium, chlorine and water increases, while their reabsorption in the renal tubules is suppressed. The drugs are administered intravenously by drip or stream at the rate of 1-2 g/kg body weight per day.
The indication for the use of osmodiuretics is early stage acute renal failure, hemolytic shock, heart failure, cerebral edema, intestinal paresis (stimulate peristalsis), diseases of the liver and biliary tract, etc. Contraindications to their use are a violation of the filtration process in the kidneys, heart failure with pronounced anasarca and other conditions of extracellular hyperhydration, intracranial hematomas.
Oxygen carriers
The creation of blood substitutes that perform the main function of blood - the transfer of oxygen to body tissues, the so-called “artificial blood”, is an important but very difficult task.
Currently, two directions are being intensively developed in the creation of blood substitutes with the function of oxygen transfer.
1. Solutions of modified hemoglobin.
This group includes gelenpol(pyridoximinated polymerized hemoglobin in human blood). Gelenpol contains a freeze-dried polymer derivative of hemoglobin with stabilizers in the form of glucose and ascorbic acid. Clinical observations and experimental data suggest that gelenpol models the respiratory function of erythrocytes and the functions of plasma proteins, increases the hemoglobin content in the circulating blood and its synthesis. Gelenpol is used for hypovolemia, anemia and hypoxic conditions.
2. Emulsions of perfluorocarbons.
The main drugs of this group are perftoran, perfucol, flusol-Da. Perfluorocarbons passively transfer oxygen and carbon dioxide in proportion to the difference in the partial pressure of the corresponding gas, increase the flow of oxygen and carbon dioxide due to an increase in their mass transfer, due to the increased solubility of gases in perfluorocarbons and the possibility free passage gases through particles.
Perfluorocarbons are chemically inert substances that do not undergo metabolic transformations in the human body.
The drugs are used as antishock and anti-ischemic agents; have rheological, hemodynamic, diuretic, membrane-stabilizing, cardioprotective and sorption properties; reduce erythrocyte aggregation. They are prescribed for acute and chronic hypovolemia (traumatic, hemorrhagic, burn and infectious-toxic shock), for microcirculation disorders, changes in tissue metabolism and metabolism, during operations on a stopped heart as the main dilutant for filling the heart-lung machine, for anti-ischemic protection of donor organs.
It should be noted that it has still not been possible to solve the problem of high-quality sterilization of blood substitutes - oxygen carriers and reducing the cost of their production. In this regard, they are used quite rarely in clinical practice.
Infusion antihypoxants.
Infusion antihypoxants are the youngest group of blood substitutes. They are designed to increase the energy potential of the cell. The main drugs are mafusolopolyoxyfumarin (contains the antihypoxant sodium fumarate) and reamberin (contains succinate). Due to the introduction of fumarate or succinate, drugs of this group restore cellular metabolism, adapting cells to a lack of oxygen; due to participation in reversible oxidation and reduction reactions in the Krebs cycle, they promote the utilization of fatty acids and glucose by cells; normalize the acid-base balance and gas composition of the blood. The drugs are indicated for hypovolemic conditions and have virtually no side effects.
Endogenous intoxication in surgery and principles of its correction. Main types of endotoxicosis. Complex treatment.
Intoxication is a pathological condition that occurs as a result of the action of toxic (poisonous) substances, endogenous or exogenous, on the body origin. Accordingly, a distinction is made between endogenous and exogenous intoxications.
Endogenous intoxications are classified depending on:
· the disease that served as the source of their occurrence (traumatic,radiation, infectious, hormonal).
· from a disorder of the physiological system, which led to the accumulation of toxic products in the body (intestinal, renal, liver).
Intoxication usually occurs as a result of the action of circulating in the bloodtoxic substances; circulation of endogenous poisons in the blood is more often referred to as toxemia, and circulation of toxins as toxemia.
Terms that indicate a substance in the blood are often used, such as azotemia.
According to the mechanism of development, the following types can be distinguished:
Retention - due to difficult excretion and retention of secretions, for example, with impaired excretory ability of the kidneys, with the accumulation of carbon dioxide and depletion of oxygen in the blood and tissues due to respiratory distress.
Resorption - due to the formation of toxic substances in body cavities during rotting and fermentation with subsequent absorption of products decay, for example, during purulent processes in the pleural cavity, Bladder or in the intestines with obstruction, intestinal, intestinal, infections, or with long-term constipation.
Metabolic - due to metabolic disorders and changes in composition tissues, blood or lymph, resulting in excessive accumulation intoxic substances in the body:
1.phenolic compounds,
2. nitrogenousbases such as betaine,
3. ammonium substances,
4.sour foodsintermediate carbohydrate metabolism (milk, etc.).
This may includeazotemia in endocrine diseases (diabetes, myxedema, Graves' and Addison's diseases, parathyroid tetany), in vitamin deficiencies, malignant neoplasms, in liver disease, when intoxication can occur due to the liver losing its ability to neutralize toxic products.
Infectious - due to the accumulation of bacterial toxins and other waste products of microbes, as well as tissue breakdown products in infectious diseases.
There may be a combination of several factors at play. Thus, with uremia, the retention of toxic products due to insufficiency of kidney function is combined with metabolic disorders. In the pathology of pregnancy, autointoxication occurs as a result of the retention of toxic metabolic products in the maternal body and, at the same time, as a result of metabolic disorders and decay processes occurring in the fetal body.
A special place is occupied by intestinal autointoxication, which I.I. Mechnikov attributed great importance in human pathology. Fermentation and putrefaction processes occur normally in the intestines. An experiment of this is the effect of extracts of intestinal contents.
When administered intravenously to an experimental animal, convulsions, central paralysis, respiratory arrest and collapse were observed. Under normal conditions, absorbed toxic substances are easily neutralized by the liver, but under pathological conditions of digestion, the processes of rotting and fermentation intensify in the intestines, as a result of which toxic substances accumulate. Absorbed in increased quantities, they can have a toxic effect. Among these toxic substances, some aromatic compounds (phenol, cresol, skatole, indole) formed from amino acids in as a result of transformationside chain as well as amino acid decarboxylation products - putrescine, cadaverine.
Intestinal autointoxication is most pronounced in cases where increased processes of putrefaction and fermentation in the intestines are combined with a weakening of the barrier function of the intestines, liver and excretory activity of the kidneys.
Under various extreme influences ( mechanical injury, extensive burn, massive blood loss) autointoxication can develop as a result of entry into the blood endotoxiaEscherichia coli, causing functional disorders in the circulatory system. Plasma obtained from animals with irreversible posthemorrhagic shock causes necrosis of the small intestinal mucosa, pyrogenic reaction and leukopenia in healthy animals. There is a concept that explains the mechanism of endotoxemia in extreme conditions of various origins. It is known that all types of shock are characterized by circulatory failure of internal organs with the subsequent development of tissue hypoxia, which inevitably leads to an increase in the activity of cells of the reticuloendothelial system (RES). As a result, the RES loses its ability to neutralize endotoxin, continuously passing from the intestine into the blood through the portal vein. Circulating quantity endotoxin constantly increases, which affects circulatory function; A vicious circle arises in which the accumulation of endoxia aggravates circulatory disorders and, above all, microcirculation.
Biophysical mechanisms, autointoxication.
The biophysical mechanisms of autointoxication are based on disturbances in physical and chemical processes in the body. It is known that in the cell there are both enzymatic and non-enzymatic systems that initiate the processes of lipid peroxidation cell membranes. As a result of these physicochemical processes, lipid oxidation products are formed - hydroperoxides, peroxides, aldehydes and ketones of unsaturated fatty acids. These products have significant reactivity; they interact with amino acids of proteins, nucleic acids and other cellular molecules, which leads to inactivation of enzymes, uncoupling of oxidative phosphorylation, and the occurrence of chromosomal aberrations. The formation of peroxides of unsaturated fatty acids in membrane phospholipids contributes to changes in the permeability of these membranes. A number of extreme factors stimulate LPO and primarily include poisoning, effects of ionizing radiation, stress.
Clinical manifestations autointoxications have their own characteristics. The course of endogenous intoxication is largely determined by the nature of the underlying disease. For example, diffuse and toxic goiter is characterized by persistent tachycardia, weight loss, exophthalmos, and symptoms of the toxic effect of an excess amount of thyroid hormones (thyrotoxicosis).
In chronic uremia, phenomena are observed in places where nitrogenous substances are released. wastes: in the larynx, pharynx, gastrointestinal tract, found on the skin accumulations of urea crystals.
With chronic endogenous intoxication, patients report malaise, irritability, weakness, headache, dizziness, nausea; exhaustion occurs and the body's resistance decreases. In some cases, autointoxication can occur in the form of severe acute poisoning (vomiting, stupor, coma). This course is typical for acute renal failure, hepatargia, and acute burn toxemia.
The occurrence of autointoxication was previously imagined only as a result of the direct effect of endotoxin on tissues and organs. However, poisonous metabolic products, like any other biologically active substances, have effects on organs and through the central nervous system. It is also possible that they irritate a vast field of receptor formations with a subsequent reflex effect on various functions of the body.
Thus, autointoxication (autos- self + intoxication) - self-poisoning with toxic substances that are produced by the body both in case of some disturbances of normal functioning and in various diseases. Basically, substances that cause autointoxication are products of metabolism or tissue breakdown.
Under normal conditions, natural metabolites are excreted from the body (through the kidneys with urine, through the colon with feces, through the skin with sweat, through the lungs with air or various secretions), or are neutralized as a result chemical transformation in the processes of intermediate metabolism. Autointoxication occurs in pathological conditions when protective devices are insufficient, for example, in case of dysfunction of the excretory organs or metabolic disorders, as well as in abnormal absorption processes from various cavities.
Basic principles of treatment:
1. In case of surgical pathology - radical surgical intervention with removal of the affected organ and effective drainage. In some cases(for example, with destructive cholecystitis, appendicitis), this can be done quite successfully, thereby interrupting further progression of endotoxicosis. In other cases, for example, when cholelithiasis is complicated by obstructive jaundice, radical surgery may not be enough, since phenomena of liver and hepatorenal failure developed. PromotionThe effectiveness of treatment of patients with obstructive jaundice can be achieved using pathogenetically based correction of hemostasis disorders.
2. Elimination of the underlying disease, which served as a source of formation and accumulation of endogenous toxic substances in the body, for example, in case of endocrine insufficiency, it is necessary to replenish the missing hormone, in case of uremia - restoration of kidney function, in case of infectious autointoxication - the use of antibiotics.
3. Elimination of toxic substances, for example, in case of autointoxication with carbon dioxide, removal of its excess by stimulating respiration, in case of autointoxication from cavities (intestines, uterus, bladder, pleural, abdominal cavities) removing the contents by washing or removing it using drainage.
4. Neutralization of toxic substances by adding disinfectants to washing liquids or introducing themperosor intravenously.
5. Strengthening the body’s excretory ability with the help of diuretics,laxatives, pathogenic drugs.
6. Reducing the concentration of toxic substances by introducing fiphysiological solutions, forced diuresis, and in case of severe autointoxication - plasmapheresis, hemodialysis, hemosorption.
Detoxification therapy is therapeutic measures aimed at stopping or reducing the intensity of the effects of toxic substances on the body.
The objectives of detoxification are to break the “vicious circles” of the process of development of endogenous intoxication and reduce the concentration of the most important endotoxins so as to unblock one’s own protection and regulation systems and make them capable of carrying out final sanogenesis.
The mechanisms available in the body to overcome intoxication are the antitoxic function of the liver and reticulocyte system, the elimination of toxic substances by the kidneys, organs of the gastrointestinal tract, etc.
In case of endogenous intoxication, detoxification therapy is carried out in the following directions.
1. Hemodilution to reduce the concentration of toxic substances, circulating in the blood. For this purpose they use drinking plenty of fluids, para-enteral introduction isotonic solutions salts, glucose.
2. Improving blood supply to tissues and organs to speed up flushing toxic substances. This purpose is served by intravenous drip administration rheologically active drugs- low molecular weight dextrans (reopolyglucin, hemodez), which also have the ability to bind toxins and promote their excretion in the urine.
3. Acceleration of the elimination of toxic substances in the urine, usually undertaken following hemodilution and the introduction of rheologically active drugs and carried out by the formation of diuresis using significant doses of fast-acting diuretics (furose mid) provided that renal function is preserved and in the absence of an artery al hypertension.
Methods of extrarenal blood purification occupy a special place. Such methods include plasma ferresis, peritoneal dialysis, IV laser, and UV irradiation of blood.
Carrying out detoxification therapy requires systematic clinical and laboratory monitoring in order to avoid its negative consequences for the patient’s condition, which may be caused by a violation of the composition of electrolytes in the body and water metabolism. The main complications may be hypervolemia and hyperhydration, leading to circulatory decompensation with the development of anasarca, pulmonary edema, and cerebral edema.
More rare side effects of therapy are a decrease in myocardial tolerance to cardiac glycosides, a decrease in the effectiveness of antibiotics and other drugs, migration of stones into the bile and urinary tract, allergic reactions on administered drugs.
BLOOD SUBSTITUTE FLUIDS(syn.: blood substitutes, plasma substitutes, blood substitute solutions, plasma substitute solutions, hemocorrectors) - drugs used for medicinal purposes as blood substitutes or correctors. K. J. used for transfusion therapy for various patol conditions; they are administered intravenously, intraarterially, intraosseously, sometimes subcutaneously or through a probe into the gastrointestinal tract. tract.
Dextran is a polymer of glucose; it is obtained by biol synthesis using a culture of Leuconostoc mesenteroides on a medium containing sucrose. In this case, the so-called native dextran with mol. weighing hundreds of millions. To reduce the mol. weight and isolation of a fraction with certain properties, native dextran is subjected to acid hydrolysis and fractionation.
The mechanism of dextran breakdown in the body was clarified thanks to the work of E. L. Rosenfeld (1955-1956), A. S. Saenko (1963-1964), Ammon (R. Ammon, 1963), who discovered an enzyme that breaks down dextran in the organs of animals and humans .
For the first time, a blood substitute based on dextran (macrodex) was proposed in Sweden in 1943 by Gronwall and Ingelmann (A. Gronwall, B. Ingelmann). Wedge, tests of the drug showed its high level of treatment. action.
In the Soviet Union, a medium-molecular dextran preparation with a mol. weighing 60,000 (+10,000) - polyglucin, developed by G. Ya. Rosenberg, T. V. Polushina and others (1954). Experimental studies conducted by N.A. Fedorov and V.B. Koziner (1956, 1974) showed that a jet infusion of polyglucin into fatally exsanguinated dogs quickly and persistently restores blood pressure and respiration. The effectiveness of the hemodynamic action of polyglucin is due to its high colloid-osmotic property and the ability to circulate in the bloodstream for a long time. Wedge, studies have made it possible to highly evaluate polyglucin, used for acute circulatory disorders. The main indications for use of the drug are traumatic, surgical and burn shock, acute blood loss.
The domestic preparation of low molecular weight dextran (average molecular weight approx. 40,000) - rheopolyglucin, developed by T. V. Polushina, G. Ya. Rosenberg and K. I. Struchkova (1967), is an analogue of the Swedish drug rheomacrodex. The drug is used for capillary blood flow disorders, for the prevention of surgical and treatment of traumatic and burn shock; in case of arterial and venous circulation disorders, for the prevention and treatment of thrombosis and thrombophlebitis, endarteritis, Raynaud's disease; during heart surgery using a heart-lung machine (it is added to the perfusion fluid); in the vascular and plastic surgery; for detoxification in case of burns, peritonitis, pancreatitis, etc. Preparations of low molecular weight dextran maintain the volume of circulating blood more briefly than preparations of medium molecular dextran, which is associated with the rapid disappearance of the polymer from the bloodstream. So, in 6 hours. after infusion, the content of the drug in the blood decreases by approximately 2 times; During this period, 60% of the drug is excreted in the urine, and after 24 hours - 70-80%.
Other antishock blood substitutes are inferior in their effect to polyglucin. Gelatin preparations that remain in a liquid state at room temperature received a positive assessment: plasmagel (France), hemogel (Germany) and the domestic preparation gelatinol (average molecular weight 20,000), developed by L. G. Bogomolova and T. V. Znamenskaya (1962 ). Gelatinol is used in the treatment of hemorrhagic, surgical and traumatic shock of the I-II degree, in preparing patients for surgery, for the purpose of detoxification for burns, for filling the heart-lung machine during hemodilution perfusions. The drug is administered intravenously or intra-arterially. The dose depends on the patient’s condition; from 250 to 2000 ml can be administered at a time. In more severe cases, its use is combined with blood transfusions.
The drug is produced in bottles of 250 and 500 ml, stored at a temperature not exceeding 22°.
Detoxifying blood substitutes used to detoxify the body must bind and be eliminated as quickly as possible toxic substances. To obtain detoxifying blood substitutes, polymers that can combine with various substances. These include polyvinylpyrrolidone (see) and polyvinyl alcohol.
Polyvinylpyrrolidone (PVP) binds and promotes the removal from the body of various dyes (Congo red, eosin, methylene blue, etc.), even those that are not excreted on their own, as well as snake venom, toxins from the causative agents of diphtheria, dysentery, tetanus, etc. With a decrease they say weight, the rate of excretion of PVP along with associated toxic compounds increases. This property is the basis for its successful use for detoxification in infections, burns, purulent-septic processes, etc. Since PVP is not broken down by the body’s enzyme systems, blood substitutes based on it do not contain high-molecular fractions, which are retained by the kidney filter and deposited in the tissues. Preparations based on it have an average mol. weight 12,600 ± 2700. They have found wide application in toxic forms of acute gastrointestinal tract. diseases (dysentery, dyspepsia, salmonellosis, etc.), especially in children; for burns and acute radiation sickness in the intoxication phase; with hemolytic disease of newborns; for peritonitis and intestinal obstruction as a means of temporary relief of the patient’s condition before surgery and as a means of detoxification in the postoperative period; in acute renal failure; for edema caused by chronic diseases, kidney diseases or toxicosis of pregnant women; for thyrotoxicosis; for sepsis; for various liver diseases (hepatitis, hepatocholangitis, acute and subacute liver dystrophy, hepatic coma).
The domestic preparation of low molecular weight polyvinylpyrrolidone - hemodez - is widely used. Similar drugs under the name periston-n, neocompensan, etc. they are produced abroad.
The mechanism of action of hemodez is based on its ability to bind toxins or breakdown products in the form of complex compounds that are quickly eliminated from the body.
Treatment the effectiveness of hemodesis is also due to the improvement of microcirculation, the elimination of stasis of red blood cells in the capillaries and precapillary network, which leads to an improvement in renal blood flow and a sharp increase in diuresis. The detoxification properties of the drug for intoxications of various origins are significantly higher than those of donor plasma.
Hemodez, like other PVP-based drugs, is administered intravenously at a rate of 40-80 drops per minute. The dose depends on the age of the patient and the degree of intoxication: for infants - 5-10 ml per 1 kg of weight, maximum dose -70 ml, for children from 2 to 5 years -100 ml, from 5 to 10 years - 150 ml, from 10 to 15 years - 200 ml] for adults maximum dose - 400 ml.
The main amount of hemodesis is excreted during the first 3-12 hours, almost completely within 24 hours.
The drug is contraindicated in severe cardiopulmonary failure, with severe allergies and cerebral hemorrhage. The drug is produced in bottles with a capacity of 100, 200, 400 ml. Store at temperatures from 0 to 20°.
This same group of blood substitutes includes a solution of low molecular weight polyvinyl alcohol - polydesis with a mol. weighing 10,000 +- 2000, developed by Z. A. Chaplygina, L. G. Mikhailova, N. V. Shostakov (1968).
The drug is used in the treatment of intoxications of various origins in surgical and infectious patients, in septic conditions in obstetric and gynecological practice. After administration, the content of the drug in the bloodstream decreases by 23% after 3 hours; after 24 hours, 25-40% of the administered amount remains; traces of the polymer are detected within 5 days. 60-75% of polydesis is excreted in urine within 24 hours. Using histochemical methods, the polymer was detected in organs and tissues within 3-7 days. after introduction. Storage at a temperature not lower than 10°. Freezing of the drug is not allowed.
Blood substitutes for parenteral nutrition
The problem of parenteral nutrition is the problem of maintaining metabolic processes in the body by directly introducing into the blood products of final enteral digestion nutrients. In this way, the processes of biosynthesis of protein structures with all their specificity must be ensured. Parenteral nutrition is becoming increasingly important.
Indications for the use of parenteral protein nutrition preparations are all diseases accompanied by hypoproteinemia of various origins, when patients cannot take food orally, as well as in preparation for surgery in weakened patients, in the postoperative period to normalize nitrogen metabolism, especially after surgical interventions on the esophagus, gastrointestinal tract. -kish. tract and during maxillofacial operations, extensive burns.
In the Soviet Union they are used for treatment. in practice, there are three types of protein hydrolysates: casein hydrolysate, developed by P. S. Vasiliev, N. A. Fedorov, N. S. Aleksandrovskaya, V. V. Suzdaleva and others (1954); hydrolysates from cattle blood proteins: hydrolysine, developed by I. R. Petrov, L. G. Bogomolova and Z. A. Chaplygina (1954), and aminopeptide (see), developed by P. E. Kalmykov and T. I. Golubev (1956). The first two drugs are obtained by acid hydrolysis, the third - by enzymatic hydrolysis (see Hydrolysates).
Of the protein hydrolysates produced abroad, aminozol (Sweden) is the most widely used. Protein hydrolysates contain protein breakdown products - amino acids and short peptides. They contain all the essential and non-essential amino acids, as well as salts that are part of the blood plasma. They are completely devoid of anaphylactogenic properties.
The digestibility of protein hydrolysates increases significantly with the addition of B vitamins, especially vitamin B12, as well as hypertonic solutions of glucose and anabolic hormones.
Hydrolysates are administered intravenously, subcutaneously or through a probe into the gastrointestinal tract. tract. Transfusion is carried out only by drop method. It is recommended to start with 20-25 drops and, if tolerated, gradually increase to 40-50 drops per minute. Daily dose- 1.5-2 l. The drugs should not be used when cardiovascular failure, cerebral hemorrhage, acute nephritis and nephrosclerosis, as well as venous disease (thrombophlebitis).
Hydrolysates are produced in bottles of 400 or 450 ml. Casein hydrolyzate is stored at temperatures from -10 to 23°; freezing of the drug is not a contraindication for use, provided the packaging is kept sealed. Hydrolysine is stored at a temperature from 4 to 20°, aminopeptide - at a temperature from 1 to 20°.
Balanced amino acid mixtures, which include only free L-amino acids, are used as preparations for parenteral protein nutrition. They have significant advantages over other drugs, because they can contain large amounts of free amino acids and can be rationally balanced in optimal ratios for protein synthesis in the body. These mixtures must contain all essential amino acids and some especially valuable non-essential ones. We must strive for such a ratio of amino acids that is optimal for satisfying the plastic and functional needs of the body; It is also advisable to take into account the characteristics of the patol and the state of the body.
Various amino acid mixtures are used: S-2 Moriamin (Japan), aminofusin, aminoplasmal (Germany), Freamin (USA), Vamin (Sweden), etc.
Based on domestic amino acids, a polyamine preparation has been developed, which is an infusion solution with all essential amino acids and the addition of some especially valuable non-essential amino acids. The energy substance includes hexahydric alcohol - sorbitol. Good tolerability and high effectiveness of the drug as a treatment have been established. parenteral protein nutrition products.
Amino acid mixtures are administered intravenously by drop method at a rate of 25-35 drops per minute. in doses of 400-1200 ml daily for the entire period of exclusion of oral nutrition (5-10 days), then depending on the severity of hypoproteinemia.
For maximum absorption the use of amino acid mixtures should be combined with the introduction of various energy components - carbohydrates (glucose, fructose), polyhydric alcohols (sorbitol), fat emulsions that help satisfy the body's energy needs, as well as stimulants of protein metabolism - vitamins and hormones.
Regulators of water-salt and acid-base balance
Deviations in water and electrolyte balance have a negative impact on the outcome of traumatic and burn shock. In these cases, rational formulations of electrolyte solutions should be used. It is permissible to limit the use of electrolyte solutions only in mild cases of burn and traumatic shock, when the injury is not complicated by significant blood loss. For more severe states of shock transfusion of electrolyte solutions should be combined with more effective transfusion agents (blood, plasma, polyglucin, etc.).
For various patol conditions, salt infusion solutions are used. The drug lactasol, developed by G. Ya. Rosenberg and I. L. Smirnova (1975), which is similar in salt composition to Ringer’s solution and additionally contains lactic acid, has proven itself well. It is successfully used to correct hemodynamics and acid-base balance blood.
Osmodiuretics also play an important role in correcting the blood composition in various pathol conditions, which include solutions of polyhydric alcohols - mannitol (see Mannitol) and sorbitol.
Saline solutions are used intravenously, subcutaneously, rectally, in a stream and drip. In case of severe traumatic and burn shock, salt solutions are recommended to be used in combination with blood, polyglucin, plasma, protein after the patient has been removed from a state of severe hemodynamic crisis. The dose of the drug for combined treatment is set individually, but it should be at least 1 - 2 liters. For mild traumatic shock and burns, the area of which does not exceed 10-15% of the body surface, it is permissible to use one saline solution in a dose of up to 3 liters. In case of acute circulatory disorders as a result of severe purulent surgical complications (peritonitis, pancreatitis, sepsis), intestinal obstruction, intestinal paresis, foodborne toxic infection, enterocolitis, dysentery, the drug is administered in a dose of 1-3 d per day and again for several days, depending on the the patient's condition.
The use of saline solutions is contraindicated in cases of decompensated alkalosis and in all cases where the introduction of large amounts of fluid into the body is not indicated (with closed skull injury, cardiac decompensation, pulmonary edema, etc.).
The drugs are produced in 400 ml bottles and stored at room temperature. Freezing is not a contraindication for use as long as the packaging is kept sealed.
Blood substitutes with oxygen transfer function
In a number of countries (USSR, USA), the possibility of using purified hemoglobin preparations for intravenous administration as a blood substitute to improve respiratory processes in the patient’s body is being studied. They are prepared by purifying erythrocyte hemolysate from stroma residues and protein procoagulants. The resulting purified hemoglobin is administered to animals in significant quantities in the experiment - up to 3 g per 1 kg of body weight.
L.G. Bogomolova and T.V. Znamenskaya (1975) developed a preparation of 3% hemoglobin - erygem, which has a positive hemodynamic, hemostatic and erythropoietic effect when administered intravenously to patients.
A new method for complete purification of erythrocyte hemolysate from stromal proteins and procoagulant activity was developed by G. Ya. Rosenberg et al. (1975).
Complex action blood substitutes
In severe shock conditions, in parallel with hemodynamic disorders, microcirculation disorders, severe tissue acidosis and accumulation of metabolic metabolites occur in the patient's body. In this regard, new complex antishock blood substitutes are being developed in order to increase treatment. the effects of existing targeted blood substitutes - polyglucin and rheopolyglucin. On their basis, other complex blood substitutes with multifunctional action are being developed: with iron salts - to enhance erythropoiesis (polyfer); in combination with mannitol - to enhance the diuretic and rheological effect of rheopolyglucin (glucoman).
To correct disturbances in blood composition, optimize its qualitative and quantitative characteristics in various pathols, conditions, special complex transfusion agents have been developed - the so-called. perfusion cocktails. They combine transfusiol. and pharmacol, activity. As a rule, all cocktails cause hemodilution). Some perfusion cocktails are used for regional perfusion of isolated areas of the body and maintaining their vital activity or therapy with high concentrations of pharmacol, drugs for the period of exclusion from the general bloodstream.
Classification, chem. The composition and purpose of the most common perfusion cocktails are presented in Table 2.
The cardiac surgical perfusion cocktail is intended for conducting controlled hemodilution (see) during open-heart surgery using a heart-lung machine. The cocktail contains gelatinol, salt components, a source of reserve alkalinity, an inhibitor of fibrinolysis activation, active antiaggregation substances, myocardial stimulants, and osmotic diuretics.
For isolated perfusion of the coronary arteries of the heart, special solution, proposed by A. A. Vishnevsky. Before perfusion of the coronary arteries of the heart, this solution is pre-cooled to a temperature of 0-4 °, due to which it takes 2-6 minutes. it is possible to cool the heart to a temperature of 36-12-8°. The solution consumption is 400-900 ml.
Nephrol, a cocktail created for filling artificial kidney devices, as well as for auxiliary perfusions in patients with kidney diseases. Its composition includes albumin solution, anabolic agents, hydrogen ion acceptors, phosphorylated carbohydrates, and salt components.
An antishock cocktail is used in cases of catastrophic hemodynamic failure and acute tissue hypoxia (cardiac arrest, asphyxia, etc.). Included in the cocktail as a transfusiol. bases include solutions of dextrans. Pharmakol, activity is provided by specific antihypoxic drugs, active bases, as well as substances that normalize the contractile function of the myocardium.
The cocktail for regional perfusion of isolated areas of the body contains low molecular weight dextran (reopolyglucin), novocaine, a direct anticoagulant, and fibrinolysis activators as a base. In this solution, depending on the purpose of administration and the nature of the patol. process include antishock drugs, antibiotics and other anti-inflammatory drugs.
The preservative cocktail is intended for perfusion of isolated organs for the purpose of their preservation. The solution is based on albumin or colloidal plasma substitutes. Its active part includes salt components, antihypoxic drugs, and energetically active substances.
Antishock and detoxification cocktails as transfusiol. the bases have ordinary salt isoionic (blood plasma) solutions, colloidal solutions or albumin. Of the existing colloidal solutions, hemodez, polydesis, polyglucin, rheopolyglucin, and gelatinol are used. Pharmakol, the activity of the cocktail is created by analgesics, sedatives, diuretics, anticoagulants, energy, antispasmodics and other agents.
Artificial blood is a blood replacement solution that simulates the most important important functions blood: filling blood vessels(hemodynamics), oxygen transport (respiratory function), delivery of nutrients (amino acids, fats, carbohydrates, vitamins) to tissues, ensuring water-salt and acid-base balance, removal of metabolic products.
Scientific research to create artificial blood began in the 60s. 20th century, did not go beyond the boundaries of laboratories and the framework of animal experiments.
In solving the problem of creating artificial blood, a leading role is played by the development of methods for obtaining transfusion components that can ensure the fulfillment of the functions of red blood cells in transferring oxygen from the lungs to the tissues in conditions of complete or partial bleeding of the body. Formulations of complex multifunctional blood substitutes are being developed based on well-known solutions such as dextran, hemodez, amino acid mixtures, lactasol, as well as the first models of blood substitutes - oxygen carriers, containing emulsions of compounds such as fluorocarbons, chemically modified hemoglobin molecules, intracomplex iron compounds, artificial red blood cells.
Emulsions of fluorocarbons and solutions of chemically modified hemoglobins, introduced into the vascular bed, make it possible to maintain the life of exsanguinated animals for several hours.
Blood-substituting fluids in military field conditions
The role of K. in military field conditions is extremely high. This is due to a certain shortage of canned blood, as well as the fact that at the first stage medical care blood transfusion is more accessible. In addition, the earlier the intravenous administration of modern blood substitutes is started in case of traumatic, burn shock, massive blood loss, or intoxication, the better the result of treatment of the affected person will be.
Of no small importance for military field conditions is the long-term preservation of blood-substituting solutions, the possibility of their instant cooking immediately before administration.
In military field conditions, isotonic is the most promising chloride solution sodium, lactasol, polyglucin, reopoliglucin, hemodez, gelatinol, etc.
Tables
Table 1. CLASSIFICATION OF BLOOD SUBSTITUTE FLUIDS USED IN THE USSR AND ABROAD (P. S. Vasiliev, O. K. Gavrilov)
|
Hemodynamic (anti-shock) blood substitutes |
Detoxification blood substitutes |
Preparations for parenteral nutrition |
Regulators of water-salt and acid-base balance |
Blood substitutes with oxygen transfer function |
Blood substitutes with complex action (multifunctional) |
|
Preparations based on dextran Medium molecular: polyglucin (USSR) chemodex (NRB) plasmodex (Hungary) dextran (Poland, Czechoslovakia) macrodex (Sweden, USA) intradex (England) Low molecular weight: reopolyglucin (USSR) hemodex (NRB) dextran-40 (Poland, Czechoslovakia) reomacrodex (Sweden, USA) lomodex (England) Gelatin preparations: gelatinol (USSR) hemogel (Germany) zhelofusin (Switzerland) plasmagel (France) |
Preparations based on low molecular weight polyvinylpyrrolidone: gemodez (USSR) periston-n (Germany) neocompensan (Austria) Preparation based on low molecular weight polyvinyl alcohol polydesis (USSR) |
Protein hydrolysates: casein hydrolyzate (USSR) hydrolysine (USSR) aminopeptide (USSR) amikin (USSR) aminosol (Sweden) amigen (USA) Amino acid solutions: polyamine (USSR) nutramine (Czechoslovakia) S-2-moriamin (Japan) aminofusin (Germany) aminoplasmal (Germany) vamin (Sweden) freamine (USA) Fat emulsion preparations: intralipid (Sweden) lipofundin (Germany) |
Saline solutions: isotonic sodium chloride solution Ringer-Locke solution lactasol (USSR) acesol (USSR) disol (USSR) trisol (USSR) chlosol (USSR) ringer-lactate (USA) Osmodiuretics: mannitol (USSR) sorbitol (USSR) |
Erigem (USSR) Fluosol-DK (Japan) Fluosol-43 (Japan) |
Polifer (USSR) Regluman (USSR) |
Table 2. CLASSIFICATION, COMPOSITION AND PURPOSE OF PERFUSION COCKTAILS
|
Cocktail name |
Purpose |
|
|
Cardiac surgical cocktails |
||
|
Perfusion cocktail with washed red blood cells (fresh or thawed) |
Washed red blood cells -400 ml Reopolyglucin (gelatinol) - 33 0 ml Albumin solution -100 ml Bicarbonate buffer solution 4% - 8 5 ml Mannitol 0.3 -1 g per 1 kg of patient weight (150 ml 5% solution per 1 liter of perfusate ). Heparin, vitamins, hormones, coronary lytics and other drugs according to indications are added to the cocktail |
Filling heart-lung machines during cardiac surgery |
|
Perfusion cocktail without donor red blood cells |
Reopolyglucin (gelatinol) - 1000 ml. Heparin, vitamins, hormones, sodium bicarbonate or Tris buffer and other drugs according to indications are added to the cocktail |
|
|
Vishnevsky perfusion solution |
Sodium chloride -5 g Potassium chloride -0.075 g Calcium chloride -0.125 g Distilled water -1,000 ml |
Perfusion of the coronary arteries to obtain deep I hypothermia of the heart |
|
Nephrological cocktails |
||
|
TsNIIGPK solution (nephrological) with washed red blood cells (fresh and thawed) |
Protein (or 5% albumin solution) - 500 ml Washed red blood cells - 500 ml. Heparin, acid-base balance regulators and other drugs according to indications are added to the solution |
Filling the dialyzer of the artificial kidney machine |
|
Whole donor blood solution |
Whole canned donor blood -500 ml Reopoliglyukin -500.ml. Heparin, acid-base balance regulators and other drugs according to indications are added to the solution |
|
|
Detoxification and anti-shock cocktails |
||
|
Sodium acetate -2 g Sodium chloride -5 g Potassium chloride -1 g Distilled water -1 l |
Combating hypovolemic infectious-toxic shock, decompensated metabolic acidosis, dehydration (El Tor cholera) |
|
|
Sodium chloride -5 g Potassium chloride -1 g Sodium bicarbonate -4 g Distilled water - 1 l |
||
|
Sodium acetate -3.6 g Sodium chloride -4.75 g Potassium chloride -1.5 g Distilled water -1l |
||
|
Lactasol |
Sodium chloride -6.2 g | Potassium chloride -0.3 g Calcium chloride -0.16 g Magnesium chloride -0.1 g Sodium lactate -3.36 g Sodium bicarbonate -0.3 g Distilled water -1l |
|
|
Sodium acetate -2 g Sodium chloride -6 gj Distilled water -1l |
Reduction of hyperkalemia and its consequences in the treatment of water-salt disorders |
|
|
Fibrinolysin-heparin polarizing cocktail |
Fibrinolysin -20,000 - 40,000 units Heparin -15 00 0 units Sodium chloride solution 10% -16 ml Magnesium sulfate solution 25% -20 ml Insulin -10 units Strophanthin solution 0.0 5% -0.5 ml Mezaton solution 1% -1 -2 ml Glucose solution 5% -250 ml |
Combating cardiogenic shock, treating coronary thrombosis, thromboembolic complications |
|
Antishock cocktails based on polyglucin, rheopolyglucin, gelatinol |
Colloidal antishock blood substitutes (polyglucin, repolyglucin, gelatinol). Various pharmacol, supplements according to indications |
Combating traumatic, burn, hemolytic shock |
|
Detoxification cocktails based on hemodez or polydesis |
Hemodesis or polydesis. Pharmakol, supplements according to indications |
Detoxification of the body in case of severe poisoning with exogenous and endogenous poisons |
|
Detoxifying Polarizing Cocktail |
Sodium chloride -6.9 g Potassium chloride -0.9 g Glucose solution 5% -1l |
|
|
Perfusion cocktail for regional perfusion |
Reopoliglyukin. Various pharmacol, additives: cytostatics, antibiotics, cellular antimetabolites, chemotherapy drugs, etc. |
Therapy malignant tumors, purulent complications in various diseases |
|
Perfusion cocktails for perfusion of isolated organs |
||
|
Solution for washing and preserving donor kidneys and hearts using the non-perfusion method (Shumakov solution) |
Calcium sulfate (solution base) -9.1 g Potassium bicarbonate -1 g Distilled water -930 ml Pharmakol, additives: Glucose solution 4 0% -50 ml Magnesium sulfate solution 25% - 15 ml Albumin solution 20% -50 ml Gamma-hydroxybutyric acid (GHB) solution 10% -8.8 ml Heparin -0.25 ml |
Washing the donor organ and preserving it in a solution at temperatures up to 0° |
|
Perfusion cocktail for isolated kidney perfusion |
Cryoprecipitated plasma. Pharmacol. additives: electrolytes, pyruvic acid |
Perfusion of a donor kidney in order to maintain its morphofunctional state necessary for transplantation |
Bibliography: Bagdasarov A. A., Vasiliev P. S. and From A. A. Issues of classification of blood substitutes, Vestn. Academy of Medical Sciences of the USSR, "JVe 4, p. 58, 1958; Vasiliev P.S. and Grozdov D.M. Functional classification of blood substitutes and its clinical rationale, Proceedings of the 12th International Congress on Blood Transfusion , p. 220, M., 1972; Vasiliev P. S. and Suzdaleva V. V. Current state problems of parenteral protein nutrition, Problems, hematol, and blood transfusion, vol. 18, no. 7, p. 3, 1973, bibliogr.; Gavrilov O.K. Development of transfusiology and the main achievements of the USSR blood service, in the book: Problems, hematol, and transfusiol., ed. O. K. Gavrilova, vol. 1, p. 24, M., 1976; Glanc R. M. The role of metabolic disorders in the digestibility of nitrogenous substances during parenteral nutrition and the use of metabolic regulators to enhance their digestibility, in the book: Ways to correct metabolic disorders in emergency and planned surgery, ed. B. D. Komarova, p. 15, M., 1976; GrozdovD. M. The importance of using protein hydrolysates in the clinic, Probl, hematol, and blood transfusion, t. 18, No. 7, p. 9, 1973; Blood substitutes, ed. A. N. Filatova, L., 1975, bibliogr.; Blood substitutes and infusion media in clinical practice, ed. V. N. Shabalina, L., 1977, bibliogr.; Polyhydric alcohols and their use in transfusiology, ed. A. N. Filatova, L., 1977, bibliogr.; Rosenberg G. Ya., Vasiliev P. S. and Grozdov D. M. Current state of the problem of blood substitutes and blood products, Sov. med., No. 9, p. 15, 1975; Fedorov N.A. and dr. Current state and prospects for the development of the problem of blood substitutes, Problems, hematol, and transfusion, blood, vol. 20, No. 11, p. 16, 1975; G g b p-w a 1 1 A. a. I ngelman V. Dextran as a substitute for plasma, Nature (Lond.), y. 155, p. 45, 1945; R e p p e W. Polyvinyl-pyrrolidon, Weinheim, 1954, Bibliogr.; W r e t 1 i n d A. The pharmacological basis for the use of fat emulsions in intravenous nutrition, Acta chir, scand., v. 128, Suppl. 325, p. 31, 1964.
P. S. Vasiliev, O. K. Gavrilov, T. V. Polushina.
Physiological and blood replacement solutions are the most complex group of injection solutions. Physiological solutions are those that, depending on the composition of the dissolved substances, are capable of supporting the vital activity of cells and living organs and not causing significant changes in the physiological balance in the body. Solutions whose properties are as close as possible to human blood plasma are called blood substitute solutions (liquids), or blood substitutes. Saline solutions and blood substitutes must first of all be isotonic. But this condition alone is not enough. They, in addition, must also be zo-ionic, i.e., contain potassium, sodium, calcium and magnesium chlorides in the proportions and quantities typical of blood serum.
Physiological solutions and blood substitutes, in addition to isotonia and iso-ionia, must also meet the requirements of isohydric acid, i.e., have a solution pH equal to the pH of the blood plasma (blood pH 7.36). At the same time, it is very important that they have the ability to maintain the concentration of hydrogen ions at the same level. In the blood, this constancy is achieved by the presence of buffers (reaction regulators) in the form of a carbonate system (bicarbonate and CO 2), a phosphate system (primary and secondary phosphates) and protein systems that are ampholytes in nature and, therefore, can retain both hydrogen and hydroxyl ions. Thanks to these buffers, the blood reaction is not easily altered. They take over and weaken all influences aimed at changing the reaction of the environment. By analogy with blood in blood substitutes and saline solutions similar pH regulators are introduced, as a result of which they become isohydric.
Physiological solutions and blood substitutes, by analogy with blood, usually contain glucose to provide nutrition to cells and create the necessary redox potential.
To further bring the solutions closer in physical and chemical properties to blood plasma, some IUDs are added to them. The latter are necessary to equate the viscosity of an isotonic sodium chloride solution with the viscosity of blood.
In addition to the above, blood replacement fluids must be devoid of toxic, pyrogenic and antigenic properties, and also not reduce blood clotting and not cause agglutination of red blood cells.
Even during the Great Patriotic War, Soviet scientists developed new original recipes for isotonic solutions, which found wide use as blood replacement fluids. In table 30 shows 7 recipes for saline solutions.
From IUDs of carbohydrate origin, dextran (proposed by TsOLIPK) has found wide use in the preparation of blood replacement solutions. Dextran is a polymer of glucose
Table 30
Physiological and blood replacement solutions (in grams per 1 l aqueous solution)
up to 20-25 °C (no more) and mix immediately before infusion.
Anti-shock solutions of the third group are complicated by the addition of viscous components. For example, the anti-shock solution of Belyakov and Petrov includes: sodium bromide 1 g, caffeine 0.2 g, morphine 0.01 g, plasma 40 ml, syncol 400 g. Another solution of this group, the anti-shock solution TsOLIPK, contains: rectified alcohol 50 ml , glucose 50 g, tecodin 0.04 g, defibrinated plasma 200 ml and water up to 500 ml. Due to the content of syncol 1 or llasma in these solutions, which are retained in the vascular bed for a long time, the mass of circulating blood increases. Weak side This group of solutions is the absence in them of substances that normalize impaired metabolism.
Antishock solutions are prepared in compliance with the same rules as isotonic and blood-substituting solutions. Alcohol is added to the sterilized solution. When preparing solutions in ampoules or hermetically sealed bottles, alcohol is introduced into the solution before sterilization. Since glucose caramelizes in an alkaline environment during sterilization, Asratyan’s anti-shock liquid is prepared, as already mentioned, separately in the form of two solutions - A and B.
