Hormonal and vitamin preparations used in obstetrics. They are designed for different purposes
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5.3. INFUSION MEDIUM IN OBSTETRIC PRACTICE
Infusion media(blood substitutes) are widely used in removing pregnant women, women in labor and postpartum from critical (extreme) conditions.
In uncomplicated pregnancy, at the time of birth, volemic changes are expressed by hypervolemic hemodilution: an increase in the volume of blood volume by 80% (1000 - 1200 ml), of which 60% (800 - 850 ml) is due to the volumetric volume (800 - 850 ml) and 20% due to the volume circulation (200 - 350 ml) ; hematocrit 30 – 35%. Rheological changes are manifested by an increase in the relative viscosity of the blood, a decrease in the COP to 22 mm Hg. Art., a decrease in osmolarity by 10 mOsm/l (275 – 280 mOsm/l), an increase in erythrocyte aggregation. Primary and secondary hemostasis increases. Compensated metabolic acidosis develops.
During pregnancy complicated by gestosis, iron deficiency anemia, placenta previa, the increase in BCC is insignificant or absent, CODE is below 22 mm Hg. Art., osmolarity below 275 mOsm/l. The increase in relative blood viscosity and erythrocyte aggregation is more pronounced. Hemostasis disorders occur as subacute or chronic DIC syndrome. Metabolic acidosis is already decompensated.
The choice of blood substitutes should be based both on the volumetric, rheological and hemostatic properties of blood and CBS of pregnant women, and on their properties.
Blood substitutes – aqueous solutions organic and inorganic substances administered parenterally to compensate for the deficiency of blood functions and correct pathological conditions of the human body.
Several classifications of blood substitutes have been proposed: A. N. Filatov (1943); A. N. Filatov, I. R. Petrov, L. G. Bogomolova (1958); A. A. Bagdasarov, P. S. Vasiliev, D. M. Grozdov (1969); A. N. Filatov, F. V. Ballyuzek (1972).
Greatest practical significance has a classification of blood substitutes by mechanism therapeutic effect, proposed by A. A. Bagdasarov, P. S. Vasiliev, D. M. Grozdov and supplemented by O. K. Gavrilov (1973):
I. Hemodynamic blood substitutes, derivatives:
– dextran;
– gelatin;
– polyethylene glycol.
II. Regulators for correcting water-salt balance and CBS:
– electrolyte solutions;
– glucose solution 5%;
– electrolyte solutions with 5% glucose;
– semi-electrolyte solutions with 5% glucose;
– osmodiuretics.
III. Solutions for “low-volume resuscitation”:
– sodium chloride solution 7.2%;
– solutions of sodium chloride 7.2% and artificial colloids.
IV. Infusion antihypoxants:
– fumarate solutions;
– succinate solutions.
V. Blood substitutes with oxygen transfer function:
– hemoglobin solutions;
– emulsions of perfluorocarbons.
VI. Complex action blood substitutes.
VII. Medicines for parenteral nutrition:
– mixtures of amino acids;
– fat emulsions;
- carbohydrates;
– all-in-one mixtures (amino acids, fats and carbohydrates).
Hemodynamic blood substitutes designed to normalize central and peripheral hemodynamics:
Treatment and prevention of absolute and relative hypovolemia;
Normovolemic hemodilution.
They are based on gelatin, dextran, HES and polyethylene glycol. The formulation of hemodynamic blood substitutes determines their following properties:
Maximum hemodynamic efficiency (volemic effect and its duration, maximum daily dose);
Side effects (direct negative impact on primary and secondary hemostasis, hemodilution, acute hyperoncotic kidney damage, the frequency of anaphylactoid reactions and the frequency of itching of the skin and mucous membranes).
Volemic effect (VE)– the ratio of the increase in BCC to the volume of the administered infusion medium as a percentage (Table 12). The volemic effect and its duration are established experimentally on volunteers who, after removing 400 ml of blood, were transfused with 500 ml of blood substitute within 15 minutes.
Table 12
Hemodynamic efficiency of colloids
Duration of volemic effect (plateau)– time during which the volemic effect will be at least 100%.
The volemic effect and its duration serve to compare hemodynamic blood substitutes with each other.
Maximum daily dose for all considered hemodynamic blood substitutes is different. In combination with crystalloids, components and blood products, they can replenish blood loss of varying sizes (Table 13). However, in practice it is necessary to take into account the severity of direct negative influence on hemostasis of dextrans and HES.
To one of side effects Some blood substitutes include their direct negative impact on primary and secondary hemostasis (Table 14).
Dextrans reduce platelet adhesiveness, reduce the activity of von Willebrand factor, have a disaggregant effect on platelets, reduce the activity of the coagulation part of the molecule factor VIII, block the fibrinogen molecule, increase the sensitivity of the fibrin clot to lysis by plasmin, and have a “siliconizing” effect. Degree negative impact dextrans is directly dependent on molecular weight and increases from rheopolyglucin to polyglucin.
Table 13
Replenishment of blood loss with hemodynamic blood substitutes
Table 14
Direct negative impact on primary and secondary hemostasis
Note: “–” – does not render; – weakly expressed; – moderately expressed;
– expressed.
HES due to the “siliconizing” effect, they reduce the adhesion and aggregation of platelets, the activity of factors VIII and IX, antithrombin-III and fibrinogen. In HES, the degree of this negative effect is directly dependent not only on the molecular weight, but also on the degree of substitution, and increases from 130/0.42 to 200/0.5 and 450/0.7. According to the instructions, dextrans and HES (200/0.5 and 450/0.7) are contraindicated in severe hemorrhagic diathesis, and caution should be exercised when using HES 130/0.42 (Venofundin).
Derivatives gelatins(gelofusin, gelatinol) and polyethylene glycol (polyoxidine) do not have a direct negative effect on primary and secondary hemostasis. In experiments in vitro when added to donor plasma from 6.7 vol% to 37.5 vol% gelofusin was not detected direct reduction ristocytin-cofactor activity of von Willebrand factor, decrease in reversible and irreversible ADP-platelet aggregation, prolongation of aPTT, decrease in the activity of factor VIII, prolongation of prothrombin time and decrease in fibrinogen concentration. Consequently, gelofusin is the hemodynamic blood substitute of choice for infusion therapy of obstetric hemorrhages, especially those caused by impaired biological hemostasis (DIC syndrome, hemodilution coagulopathy, von Willebrand disease, etc.).
Hemodilution effect. Each intravenously administered 500 ml of hemodynamic blood substitute for 15 minutes reduces the hematocrit by an average of 4–6%. With a hemodilution decrease in hematocrit of less than 28%, hemodilution coagulopathy and thrombocytopenia may develop.
Colloid osmotic pressure (COP ) is created by blood plasma proteins (mainly albumin) and is one of the regulators of transcapillary metabolism. According to Starling's law, the difference between the forces of filtration and reabsorption in the arterial section of the capillary reaches 7 mm Hg. Art. (under this pressure, fluid from the capillaries is filtered into the tissue), and at the venous pressure - 7 - 8 mm Hg. Art. (under this pressure, fluid from the tissues enters the vascular bed). From 33 mm Hg. Art. reabsorption forces account for 25 mm Hg. Art. Gelatinol (16.2 – 21.4 mmHg) and stabizol (18 mmHg) have COD within normal limits (16.7 – 24.2 mm Hg). In 6% of HES (130/0.42 and 200/0.5), the COD ranges from 28 to 36 mm Hg. Art. Consequently, when administering a blood substitute with a COD higher than that of blood plasma, conditions are created for the flow of fluid from the interstitial space into the vascular bed. However, when using hyperoncotic solutions: dextrans, especially low molecular weight dextran - reopolyglucin (COD is 90 mm Hg); 10% solutions of HES 200/0.5 (COD is 65 - 80 mm Hg) are more characterized by the development of the so-called acute hyperoncotic kidney injury syndrome. There are several hypotheses for the pathogenesis of kidney damage when using colloidal solutions. According to one of them, the development of acute renal failure(OPN) is associated with the accumulation of low molecular weight fractions in renal tubules and an increase in urine osmolarity, which triggers necrotic changes in tubular epithelial cells. According to another, kidney damage is caused by an imbalance between hydrostatic pressure (renal perfusion pressure) and oncotic pressure (blood plasma) on the glomerular membrane. An increase in plasma oncotic pressure is associated with the use of hyperoncotic solutions up to resorption glomerular filtration, which ultimately leads to ischemia and damage to the tubular epithelium.
When administering colloidal blood substitutes of any class, problems may occur. anaphylactoid reactions(Table 15). According to the classification of Ring and Messmer, they are divided into mild (grades 1 - 2) and life threatening, or severe (grades 3–4). The frequency (%) and severity (grade 1 - 4) of their occurrence should be indicated in the instructions for use of these drugs. For example, for albumin - 0.099%, gelatinol - 0.155%, gelofusin - 0.0077%, dextrans - up to 7%, HES 200/0.5 - up to 0.047% and for HES 450/0.7 - up to 0.085%. In order to prevent anaphylactoid reactions, a biological test should be performed.
Table 15
Degrees of anaphylactoid reactions according to Ring and Messmer (1977)
Long-term daily use of HES in medium (500 ml) and high (1000 ml) doses (total course dose of HES more than 300 g) can cause itchy skin And genitals varying intensity and duration. It is associated with the deposition of HES molecules along the nerves and disappears only after the removal or breakdown of HES. Classic antihistamines, antipruritics, ultraviolet therapy and antipsychotics are useless in treating this type of itching.
Hydroxyethyl starches (130/0.42; 200/0.5 and 450/0.7) have cytoprotective properties. Highly branched starch molecules form “rivets” in the spaces between endothelial cells throughout basement membrane, effectively eliminating transcapillary leakage that occurs in many pathological conditions, and protecting endothelial cells from damage by various agents.
The main route of elimination of all hemodynamic blood substitutes is in the urine; only HES is first broken down into fractions by blood amylase. In patients with renal failure there is decreased elimination of blood substitutes.
Indications for the use of 6% HES and gelofusin depend not only on the level of hypovolemia, but also on the presence of hemorrhagic diathesis in the patient (Table 16).
Regulators of water and electrolyte balance And CBS designed to correct violations:
Water exchange;
Electrolyte metabolism;
Metabolic acidosis (metabolic acidosis).
Table 16
Indications for the use of 6% HES and gelofusin for hypovolemia
Note: “+” – shown; “–” – not shown.
These solutions can be divided into five groups:
1) electrolyte solutions;
2) electrolyte concentrates;
3) osmodiuretics;
4) glucose solution 5%;
5) semi-electrolyte solutions.
The recipe of electrolyte solutions (Tables 17, 18) determines their properties - osmolarity, isotonicity, ionicity, reserve alkalinity.
In relation to the osmolarity of electrolyte solutions to blood, they exhibit an iso-, hypo- or hyperosmolar effect.
Isoosmolar effect. Water, chemically bound with ions, is distributed between the intravascular and extravascular spaces as 25% to 75%. The volemic effect (the increase in the volume of blood volume to the volume of the injected infusion medium in %) will be 100% with jet administration and about 25% 30 minutes after the end of administration. These solutions are indicated for the treatment of hypovolemia (Table 19).
Depending on the electrolyte content in the solution, they can be isotonic (sodium chloride solution 0.9%), hypotonic (disol, acesol) and hypertonic (sodium chloride solution 10%, potassium chloride solution 4%, sodium bicarbonate solution 4.2 and 8 ,4 %). The latter are called electrolyte concentrates and are used as an additive to infusion solutions (5% glucose solution, Ringer acetate solution) immediately before administration.
Depending on the number of ions in the solution, monoionic (sodium chloride solution) and polyionic solutions (Ringer's solution, etc.) are distinguished.
The introduction of reserve alkalinity carriers into electrolyte solutions makes it possible to carry out rapid (bicarbonate) and delayed (acetate, lactate, malate) correction of metabolic acidosis or maintain the existing CBS (see Table 17).
(see Table 17) depending on the composition are used for:
Isotonic dehydration of the extracellular space (due to water chemically bonded with ions);
Electrolyte metabolism disorders (due to Na +, K +, Ca 2+, Mg 2+, Cl − ions);
Unchanged CBS (due to BE from –3 to +2.5 mmol/l);
Metabolic acidosis (due to BE more than +3 mmol/l).
Table 17
Isotonic electrolyte solutions
Table 18
Electrolyte solutions (isotonic) 5% glucose
Table 19
Distribution of water between the physiological spaces of the body 30 minutes after the administration of blood substitutes
Table 20
Rate of administration and maximum doses isotonic electrolyte solutions
Isotonic electrolyte solutions can be administered either peripherally or via central veins. The rate and maximum daily doses for adults are given in table. 20.
Electrolyte solutions(isotonic) with 5% glucose are used for:
Isotonic or hypotonic dehydration of the extracellular space;
Electrolyte metabolism disorders (due to Na +, K +, Ca 2+, Mg 2+, Cl – ions);
Metabolic acidosis (due to acetate, malate) and to partially cover energy needs.
Infusion antihypoxants(Mafusol, Reamberin, Sterofundin G-5) are intended to increase the energy potential of the cell (Table 21). They perform the following functions:
1) restore cellular metabolism, activating cell adaptation to oxygen deficiency, due to participation in reversible oxidation and reduction reactions in the Krebs cycle;
2) promote recycling fatty acids and glucose by cells;
3) normalize acid-base balance And gas composition blood;
4) platelets disaggregate.
Table 21
Infusion antihypoxants
Infusion antihypoxants are indicated for the treatment and prevention of absolute and relative hypovolemia (blood loss, shock), hypoxic conditions of various etiologies and intoxications.
5.4. BLOOD COMPONENTS IN OBSTETRIC PRACTICE
Blood components– blood components used for medicinal purposes, which can be prepared from whole blood using various methods.
Blood components include:
Cellular components (erythrocytes, platelets, leukocytes);
Plasma components (cryoprecipitate, cryosupernatant plasma).
Erythrocyte-containing components(EC) are intended to replace blood loss and treat anemia.
The doctor may have several ECs at his disposal (Table 22).
The choice of EC to replace blood loss depends on its composition and properties.
Massive blood loss of 25 - 30% of the bcc, accompanied by a decrease in hemoglobin levels below 70 - 80 g/l, hematocrit below 25% and the occurrence of circulatory disorders, is an indication for EC transfusion. It is believed that with normal gas exchange in the lungs critical level delivery of oxygen to tissues (Ca O 2) 10 ml/dl is carried out with hemoglobin 65 – 70 g/l.
One dose of transfused donor EC increases the recipient's hemoglobin content by an average of 10 g/l and hematocrit by 4–6%.
Native EC should be stored for up to 3 days in a CPD (citrate, phosphate, dextrose) or glugitsir preservative, up to 5 days in a CPDA-1 preservative (citrate, phosphate, dextrose, adenine) and up to 7 days in a SAGM resuspension solution. These recommendations are due to the fact that the main and leading role in the oxygen transport function of donor red blood cells is played by the intermediate component of glycolysis - 2,3-bisphosphoglycerate. After 7 days of storage in the preservative CPD or glugitsir, after 10 days in the preservative CPDA-1 and after 15 days in the resuspension solution SAGM, the content of this enzyme decreases to a level at which the dissociation of oxyhemoglobin and the transfer of oxygen to tissues is difficult. Its content in donor red blood cells after transfusion is restored in the recipient’s bloodstream only after 12–24 hours.
Table 22
Composition of erythrocyte-containing components
EC should be poured through a filter with a pore size of no more than 170 - 200 microns, since platelet aggregates spontaneously form from the first hours of storage. During the day, leukocytes are included in them and then fibrin threads are formed around the platelet-leukocyte aggregates. During subsequent storage, the number of microaggregates ranging in size from 4 to 200 microns progressively increases. Removal of microaggregates from 30 to 40 microns during transfusion prevents microthromboembolism of pulmonary vessels and the development respiratory distress syndrome. The number of microaggregates can be reduced in two ways: 1) use erythrocytes with a removed buffy platelet layer or those depleted of leukocytes; 2) use microaggregate filters when transfusing red blood cells.
The use of red blood cells depleted of leukocytes (less than 1 × 10 6 per dose) helps prevent a number of post-transfusion reactions and complications: HLA alloimmunization, hyperthermic non-hemolytic reaction, post-transfusion purpura, transmission of cytomegalovirus and Epstein-Barr virus, as well as reduce the incidence of immunosuppression and respiratory distress -syndrome.
Table 23
Platelets: restored
Platelets: restored– component donated blood human, obtained from whole blood and containing in a dose the majority of platelets in a therapeutic effective form(Table 23).
Recovered platelets are used for clinical significant bleeding associated with platelet deficiency.
The dose of transfused donor platelets increases their number in the recipient by 7 ⋅ 10 9 /l.
Fresh frozen plasma(FFP) is a component of human donor blood for transfusion, obtained from either whole blood or apheresis-derived plasma, frozen for a specified period of time at a specified temperature to ensure preservation functional state labile coagulation factors.
FFP contains albumin, immunoglobulins, and at least 70% of the original level of factor VIII and at least the same amount of other labile coagulation factors and natural inhibitors. A dose of FFP (250 ml) contains an average of 0.75 g of fibrinogen and at least 150 IU of factor VIII.
Defrosting FFP can be done in a water bath (37 °C for 20 minutes) or using a rapid plasma defroster for 12 - 15 minutes. Factor VIII activity is better preserved when using a rapid plasma thawer.
Immediately after thawing, FFP should be poured through a filter with a pore size of no more than 170 - 200 microns. Repeated freezing is unacceptable.
FFP can be used for coagulation disorders, especially in those clinical cases when there is a deficiency of several coagulation factors, and in the absence of a suitable virus-inactivated stable drug.
FFP should not be used:
To correct BCC deficiency;
In the absence of coagulation factor deficiency;
As a source of immunoglobulins;
In patients with plasma protein intolerance.
Cryoprecipitate - a component of human donor blood obtained during subsequent processing of FFP and containing a fraction of plasma cryoglobulins.
The drug contains a dose of at least 70 IU of factor VIII, at least 0.14 g of fibrinogen, and the main part of von Willebrand factor, factor XIII and fibronectin.
Cryoprecipitate can be used for:
Conditions with factor VIII deficiency (hemophilia A, von Willebrand disease with the unavailability of appropriate virus-inactivated drugs);
Other conditions of complex deficiency of coagulation factors, such as disseminated intravascular coagulation;
Fibrinogen deficiency (qualitative and quantitative).
Cryosupernatant plasma– a component of human donor blood prepared from plasma by removing cryoprecipitate.
The drug contains the same amount of albumin, immunoglobulins and blood clotting factors as in FFP, with the exception of those remaining in the removed cryoprecipitate.
Its shelf life: 24 months. at temperatures below –25 °C, 3 months.
at temperatures from −18 °C to −25 °C.
Defrosting can be done in a water bath (37 °C for 20 minutes) or using a rapid plasma defroster for 12 - 15 minutes.
Immediately after thawing, the plasma should be poured through a filter with a pore size of no more than 170 - 200 microns. Repeated freezing is unacceptable.
The drug can be used for acquired coagulopathies, DIC syndrome blood (if the patient's fibrinogen level is above 1.5 g/l).
Only ABO compatible plasma should be used.
Informed voluntary consent of the patient for blood transfusions. Fundamentals of legislation Russian Federation on protecting the health of citizens dated July 22, 1993 No. 5487-1, orders of the Ministry of Health of the Russian Federation, guidelines The compulsory health insurance fund requires prior informed voluntary consent(IDS) of the patient for any medical intervention.
Transfusion of donor blood and its components, even without a defect in their conduction, is associated with the development of reactions and complications and requires IDS for their implementation.
The proposed form for the IDS does not provide for risks associated with violations of the transfusion methodology and technique.
Before a planned manipulation or surgical intervention, which may require a transfusion of donor blood or its components, the attending physician and (or) anesthesiologist fills out the patient’s IDS (Appendix).
In emergency situations requiring urgent decisions, when the patient’s condition does not allow him to express his will, and medical intervention is urgent, the issue of transfusion of donor blood or its components in the interests of the patient is decided by a council, and if it is impossible to convene a council, by the attending (duty) doctor directly followed by notification of the clinic official.
IDS documents are pasted into the medical history.
1. Helmodynamic (anti-shock)
Low molecular weight dextrans - reopolyglucin
2. Medium molecular dextrans - polyglucin
3. Gelatin preparations - gelatinol
11. Detoxification
1. Low molecular weight polyvinylpyrrolidone- hemodesis
2. Low molecular weight polyvinyl alcohol - polydesis
111. Preparations for parenteral nutrition
1. Solutions of amino acids.
2. Protein hydrolysates.
3. Fat emulsions - intralipid, lipofundin
4. Sugars and polyhydric alcohols - glucose, sorbitol, fructose
1V. Regulators of water-salt and acid-base status
1. Saline solutions- isotonic sodium chloride solution, Ringer's solution, lactosol, sodium bicarbonate solution, trisamine solution
MAIN TYPES OF BLOOD SUBSTITUTES
Blood substitutes with hemodynamic (anti-shock) action
High-molecular blood substitutes are mainly hemodilutants, they help increase blood volume and thereby restore blood levels. blood pressure. 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, blood loss, when necessary, first. The turn is to restore the volume of circulating blood and prevent the complex of shock reactions caused by small output syndrome. Low-molecular blood substitutes improve capillary perfusion, circulate in the blood for less time, are excreted faster by the kidneys, carrying excess fluid. These properties are used in the treatment of capillary perfusion disorders, to dehydrate the body and combat intoxication through the removal of toxins through the kidneys.
Polyglucin - colloidal solution of glucose polymer - dextran bacterial origin, containing a medium molecular weight (molecular weight 60,000-10,000) fraction of dextran, the molecular weight of which approaches that of albumin, which ensures normal colloid-osmotic pressure of human blood. The drug is a 6% solution of dextran in an isotonic sodium chloride solution. The pH of the drug is 4.5 - 6.5. Available in sterile form in 400 ml bottles, stored at temperatures from -10 to +20 ˚С, shelf life - 5 years. Possible freezing of the drug after thawing medicinal properties are being restored.
The mechanism of the therapeutic effect of polyglucin 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. When polyglucin is administered, the volume of blood plasma increases by an amount greater than the volume of the administered drug. The drug circulates in the vascular bed for 3 - 4 days; its half-life is 1 day.
In terms of hemodynamic effect, polyglucin is superior to all known blood substitutes, due to its colloidal osmotic properties it normalizes arterial and venous pressure, improves blood circulation. Polyglucin contains up to 20% low-molecular fractions of dextran, which can increase diuresis and remove toxins from the body. Polyglucin promotes the release of tissue toxins into the vascular bed and then their removal by the kidneys. Indications for its use are as follows: 1) shock (traumatic, burn, surgical); 2) acute blood loss; 3) acute circulatory failure in severe intoxication (peritonitis, sepsis, intestinal obstruction and etc.); 4) exchange blood transfusions for hemodynamic disorders.
The use of the drug is not indicated for skull trauma and increased intracranial pressure. A single dose of the drug is 400 - 1200 ml, if necessary it can be increased to 2000 ml. Polyglucin is administered intravenously by drip and stream (depending on the patient’s condition). In emergency situations they begin jet injection drug, then when increasing blood pressure switch to drip infusion at a rate of 60 - 70 drops per minute.
Reopolyglucin is a 10% solution of low molecular weight (molecular weight 35000) dextran in an isotonic sodium chloride solution. Reopolyglucin is capable of increasing the bcc; every 20 ml of solution binds an additional 10 - 15 ml of water from the interstitial fluid. The drug has a powerful disaggregating effect, helps eliminate blood stasis, reduce its viscosity and increase blood flow, i.e. improves rheological properties blood and microcirculation. Reopoliglucin has a great diuretic effect, so it is advisable to use it for intoxication. The drug leaves the vascular bed within 2-3 days, but the main amount is excreted in the urine in the first day. Indications for use of the drug are the same as for other hemodynamic blood substitutes, but rheopolyglucin is also 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. Contraindications to the use of the drug are chronic diseases kidney
Gelatinol is an 8% solution of partially hydrolyzed gelatin in an isotonic sodium chloride solution. The molecular weight of the drug is 20,000. Due to its colloidal properties, the drug increases the bcc. They mainly use the rheological properties of gelatinol, its ability to thin the blood and improve microcirculation. Nutritional value the drug does not possess, it is excreted completely within 24 hours in the urine, and after 2 hours in bloodstream only 20% of the drug remains. The drug is administered by drip and stream intravenously, intra-arterially, it is used to fill the apparatus cardiopulmonary bypass. Total dose up to 2000 ml. Relative contraindications The drug can be used for acute and chronic nephritis.
Transfusion therapy in emergency situations (in the treatment of shock, acute blood loss, acute vascular insufficiency) you should start with means that can quickly restore your bcc. The use of donor blood leads to a loss of 20 - 30 minutes of time, which is necessary to determine the blood group, compatibility tests, etc. In terms of the ability to restore bcc, donor blood has no advantages over colloidal plasma substitutes. In addition, with shock and a pronounced deficiency of bcc, a disorder of microcirculation occurs - a disruption of capillary blood flow, the causes of which are an increase in blood viscosity, slugging shaped elements and microthrombosis, which are aggravated by transfusion of donor blood. In this regard, transfusion therapy in case of shock and even blood loss should be started with the intravenous administration of anti-shock blood substitutes - polyglucin and rheopolyglucin.
Blood substitutes for detoxification action
Hemodez - 6% solution of low molecular weight polyvinylpyrrolidone in a balanced solution of electrolytes. Available in bottles with a capacity of 100, 200, 400 ml, stored at temperatures from 0 to +20 ˚С, shelf life -5 years. Hemodez has good adsorption ability: it binds toxins circulating in the blood, including bacterial ones, partially neutralizes them and removes them in the urine. The drug is quickly excreted by the kidneys: after 4 - 6 hours, up to 80% of hemodesis is released. Hemodez has the property of eliminating the stasis of red blood cells in the capillaries, which is observed during intoxication. By improving capillary perfusion, the drug is able to remove toxins from tissues. Average single dose hemodesa - 400 ml. The rate of administration of the drug is 40 - 50 drops per minute. Indications for the use of the drug are severe purulent-inflammatory diseases accompanied by purulent-resorptive fever, purulent peritonitis, intestinal obstruction, sepsis, burn disease, postoperative and post-traumatic conditions.
Related information.
The modern classification of blood substitutes is based on the characteristics of their action. There are 6 groups of blood substitutes:
Hemodynamic (anti-shock);
Detoxification;
Preparations for parenteral nutrition;
Correctors of water-electrolyte metabolism and acid-base balance;
Oxygen carriers;
Complex action drugs
Hemodynamic (volemic) blood substitutes.
The main pharmacological property of this group of drugs is the ability to increase blood volume and thereby eliminate hypovolemia. Volemic drugs include
Saline solutions
Colloidal plasma substitutes
Dextrans
Hydroxyethyl starch preparations (HES, HES)
Gelatin preparations
Polyethylene glycol preparations
Blood plasma preparations
Poliglyukin (Macrodex, Dextran -70) . Medium molecular dextran. M=50-70 thousand D, which approximately corresponds (slightly higher) to the molecular weight of human albumin. Available in the form of a 6% solution with the addition of 0.9% sodium chloride. It has a hyperoncotic effect, retaining in the vascular bed (or attracting into the vascular bed from surrounding tissues) per volume of the administered drug up to 3 volumes of water. In this regard, it quickly raises blood pressure during hemorrhagic shock. The volemic effect lasts for at least 12 hours. Against the background of oliguria and during infusion into large doses often provokes “dextran syndrome”).
Reopoliglyukin (Reomacrodex, Dextran -40) Low molecular weight dextran. M=30-40 thousand D. Available in the form of a 10% solution (Reomacrodex - 12%) with the addition of 0.9% sodium chloride. Has a pronounced antiplatelet effect. Isooncotic. It remains in the vascular bed for about 8-12 hours. “Dextran syndrome” rarely causes, only against the background of prolonged hypotension and oliguria.
HES 6% 0.5/200 (Volecam, HAES-steril 6%, Refortan, Infucol) – the most commonly used drug is HES. Isooncotic solution. Effectively replenishes intravascular volume and improves microcirculation. The maximum dose is up to 1.5 liters per day, limited due to the hypocoagulative effect of the drug. The duration of the volemic effect is 3-4 hours.
HES 10% 0.5/200 (HAES-steril 10%, Hemohes 10%, Refortan plus) – pharmacological effects are similar to HES 6% 0.5/200, but due to hyperoncoticity they increase the intravascular volume to 150% of the volume of the administered drug.
HES 6% 0.4/130 (Voluven) – differs from HES 0.5/200 by a lesser effect on hemostasis, as a result of which the daily infusion volume can reach 3.0-3.5 liters.
HES 6% 0.7/450 (Stabizol) – significantly inhibits both primary and secondary hemostasis, but also improves microcirculation more significantly than other drugs. The effect lasts for at least 6-8 hours. For the treatment of acute blood loss, HES is less preferred than other drugs.
Gelatinol – 8% solution of partially hydrolyzed edible gelatin in an isotonic sodium chloride solution. M=15-25 thousand, which corresponds to the molecular weight of human albumin. The volemic effect 1 hour after intravenous administration is 60% of the infusion volume. The maximum single dose is 2 liters, limited by the ability of gelatinol to stimulate the release of interleukin-1b and histamine, and reduce fibronectin concentrations. As a result, the endothelium is sharply damaged and the permeability of the capillary wall increases. There are opinions that Gelatinol can increase bleeding time, impair clot formation and platelet aggregation, which is due to the increased content of calcium ions in solutions.
A special situation regarding the safety of using gelatin solutions has arisen due to the threat of the spread of the causative agent of transmissible spongiform encephalopathy of large cattle(“mad cow disease”), which is not inactivated by conventional sterilization regimes. In this regard, there is information about the danger of infection through gelatin preparations.
Gelofusin – 4% solution of succinate gelatin (modified liquid gelatin, MFG). M=30 thousand D. Isooncotic. The volemic effect lasts for at least 5 hours. Reduces blood viscosity and improves microcirculation. 90-95% of the drug is excreted by the kidneys. No damaging effects on the kidneys and other parenchymal organs or effects on hemostasis were detected. Due to the virtual absence of side effects, the volume of maximum infusion is not limited. Today, Gelofusin is the closest thing to an “ideal volumetric plasma substitute.”
Polyoxidine. M-20 thousand D. Isooncotic (?). The duration of the volemic effect is not precisely established. The maximum single dose for adults is 1200 ml. Has disaggregant properties. May cause nausea, pyrogenic and allergic reactions.
METHYLERGOMETRINE (increases uterine contractions), ERGOMETRINE MALEATE (increases tone and increases the frequency of uterine contractions), ERGOTAL (Ergotalum)
A mixture of ergot alkaloid phosphates. pharmachologic effect. Increases the tone of the uterine muscles and increases the frequency of its contractions.
Indications for use. Uterine bleeding caused by atony (loss of tone) of the uterus; to speed up reverse development uterus in postpartum period.
ERGOTAMINE (Ergotamin)
Pharmachologic effect. Increases the frequency and amplitude of uterine contractions, and also has a sympatholytic and sedative (calming effect on the central nervous system) properties.
Indications for use. Uterine bleeding, atony (loss of tone) of the uterus, incomplete abortion; migraine.
OXYTOCIN Pharmacological action. Causes strong contractions of the muscles of the uterus (especially during pregnancy).
Indications for use. To stimulate labor activity, with hypotonic uterine bleeding (bleeding associated with decreased uterine tone) in the postpartum period. Can be used to artificially induce labor (in case of pregnancy complications).
PITUITRIN Pharmacological action. It has oxytocic (stimulating contractions of the uterine muscles), vasopressor (vasoconstrictor) and antidiuretic (reducing urine secretion) effects.
Indications for use. To stimulate and enhance uterine contractions during weak labor, post-term pregnancy, hypotonic bleeding (associated with decreased uterine tone) and to normalize uterine involution (uterine contractions in the postpartum period).
NETTLE EXTRACT LIQUID (Extractum Urticaefluidum)
Pharmachologic effect. Has a hemostatic effect in various bleedings. Strengthens uterine contractions and increases its tone.
Indications for use. Atony (loss of tone) of the uterus; atonic or hypotonic uterine (associated with decreased uterine tone) bleeding; to accelerate the involution (contraction) of the uterus in the postpartum period. Bleeding from respiratory tract, gastrointestinal tract; nosebleeds.
None of the existing blood substitutes performs the entire complex of functions inherent in blood, and, having only some properties characteristic of blood plasma, they can only be considered plasma substitutes. This gives reason to call solutions intended for intravenous therapy plasma substitutes, vascular fillers, or infusion solutions, which creates terminological confusion. If we approach this problem as a problem of modeling various functions and properties of blood, it is possible to create individual compounds that can effectively perform one function in the body or, like blood, a number of them. Only in this case can the infusion solution obtained from these compounds be called a blood substitute. Moreover, if it performs one function, then it is a drug with a targeted therapeutic effect, i.e. single-function blood substitute; If it has a number of functions, then it is a complex therapeutic drug - a multifunctional blood substitute.
The modern classification of blood substitutes is based on the characteristics of their action. According to this classification, there are 6 groups of blood substitutes: 1) hemodynamic (anti-shock); 2) detoxification; 3) blood substitutes for parenteral nutrition; 4) correctors of water-electrolyte metabolism (VEO) and acid-base balance (ABC); 5) oxygen carriers; 6) blood substitutes with complex action.
Regardless of the group and nature of action, all blood substitutes must have physicochemical and biological properties similar to those of blood plasma, i.e. must be: a) isoionic (have an ionic composition similar to that of blood plasma); b) isotonic (osmotic pressure of blood plasma 7.7 atm); c) isosmolar (290 – 310 mOsmol/l); d) not anaphylactogenic (should not cause sensitization of the body or anaphylactic reactions); e) relatively inert to the hemostatic system; f) non-toxic; g) pyrogen-free; h) immunoinert; i) easy to manufacture; j) must withstand the necessary sterilization regimes; l) must be stored for a long time normal conditions and during transportation.
In addition to the basic general properties, blood substitutes must have properties that depend on their functional nature.
Group 1 – hemodynamic(volemic, antishock) blood substitutes combine drugs that give the greatest effect in infusion therapy for most critical conditions accompanied by hypovolemia. Moreover, the volemic effect is achieved as a result of not only the direct circulation of the drug introduced into the bloodstream, but also the attraction of fluid from the extravascular sector, and in some cases (applies to individual drugs) - due to a decrease in the intensity of deposition processes due to the implementation of the positive rheological properties of the blood substitute. This ability to increase BCC is characterized by a volemic coefficient. The latter is the amount of increase in the volume of intravascular fluid (in ml) for each milliliter of blood substitute introduced into the recipient’s vascular bed. For most antishock blood substitutes, it approaches 1 and thus creates a volemic “doubling effect” of the injected volume.
The mechanism of action of antishock blood substitutes is determined mainly by their biophysical properties, which can be clearly seen in the example of the action of polyglucin. Thus, an increase in BCC is achieved by prolonged circulation this drug in the vascular bed due to the content of colloidal particles with a molecular weight of more than 40,000 daltons (D), which are normally not filtered by the kidneys. Consequently, the rate of polyglucin elimination depends on the conditions of its breakdown in the body. As a rule, domestic colloidal blood substitutes (including polyglucin, the mass of particles of which ranges from 15,000 to 150,000 D) are heterogeneous in molecular weight composition, which determines the diversity of their functions and mechanism of action. Thus, low-molecular fractions of the drug have a rapid hemodynamic effect (high colloid-osmotic pressure, accelerated inflow from the extravascular space), significantly improve the rheological characteristics of the blood, thereby stabilizing microcirculatory homeostasis and the function of the main parenchymal organs, but quickly leave the vascular bed. At the same time, high-molecular fractions of the drug can enhance platelet and erythrocyte aggregation, bind fibrinogen, worsen the rheological characteristics of blood, and remain in the body for a long time (up to several months). The main, medium-molecular mass of the drug, as it were, eliminates the result of the influence of these two simultaneously and oppositely acting mechanisms, which ensures a persistent volemic and moderate rheological effect as a whole. Knowledge of all these features of the drug’s action allows us to more clearly determine the indications and contraindications for its use, taking into account the patient’s condition.
Poliglyukin. This is a transparent, colorless liquid, which contains medium molecular dextran (60 g), sodium chloride (9 g), ethyl alcohol (0.3%), water for injection (up to 1000 ml).
The large molecular weight and high COD of polyglucin determines its retention in the vessels, as well as an increase in the central volume and volume of extracellular fluid due to the redistribution of fluid from the intracellular to the extracellular sector (1 g of dry matter contributes to the redistribution of up to 26 ml of fluid). An increase in the volume of extracellular fluid is also ensured by the osmotic property of sodium chloride; the total volumetric coefficient is quite high.
The bulk of polyglucin introduced into the blood is excreted in the urine (in the first 24 hours - up to 50%), a small part (about 2%) - in feces, the rest is retained (up to 30-60 days or more) in the cells parenchymal organs(in the spleen, liver, kidneys, heart, lungs) and muscles, where it is broken down by dextran glucosidase to carbon dioxide and water at a rate of approximately 70 mg/kg/day.
Polyglucin is indicated in all cases of hypovolemia without severe microcirculation disorders; acute circulatory failure due to peritonitis, intestinal obstruction, pancreatitis, collapse, burn, etc.; if it is necessary to provide normovolemic intraoperative hemodilution, perform an operation using artificial circulation, etc. There are no absolute contraindications for the use of polyglucin; Closed craniocerebral injury with clinical manifestations of intracranial hypertension, cardiopulmonary insufficiency of III–IV degree, expressed by microcirculation disorders (“microcirculation deficiency”), DIC syndrome in stages II–III, acute renal failure are considered relative.
Polyglucin solutions are non-toxic and non-pyrogenic. However, it belongs to substances foreign to the body, and if in the 60–70s the anaphylactic complications caused by it (usually in the form of reactions) were relatively rare and were explained by the insufficient degree of purity of individual batches of the drug, then in last years It has been proven that in humans, as a result of the administration of dextran, protein-polysaccharide complexes are formed that are antigenic (this property is inherent mainly in high-molecular fractions). Thus, the entry of polyglucin into the body may be accompanied by an anaphylactic reaction of varying severity, up to the occurrence of fatal anaphylactic shock. To prevent them, before infusion of polyglucin, it is necessary to carry out the same biological test as when administering whole blood. A more effective method of preventing reactions is the creation of new drugs with narrowly targeted action that do not contain high-molecular fractions of dextran.
Rondex(65000±5000 D) – sterile pyrogen-free 6% solution of radiation-modified dextran in 0.9% sodium chloride solution. The relative viscosity of the drug does not exceed 2.8. It is a transparent yellow liquid, odorless. Available in hermetically sealed 400 ml bottles.
Rondex, due to the narrow molecular weight distribution of its fractions, has better functional characteristics compared to polyglucin and similar foreign drugs. By normalizing central hemodynamics, it actively restores peripheral blood flow by reducing total peripheral resistance. Rondex is able to increase the electrokinetic potential of the endothelium and red blood cells, does not have an accelerating effect on the first phase of hemocoagulation, and suppresses the adhesive properties of platelets and the intensity of their aggregation. These properties are similar to those of rheopolyglucin.
Rondex is used for the prevention and treatment of various types of shock, blood loss, circulatory disorders during surgical interventions, resuscitation and intensive care, hemorheology and blood clotting disorders, for detoxification, for the treatment of patients with acute and chronic renal failure, etc. Its total daily dose can be increased to 2 liters or more.
Medium-molecular colloidal anti-shock blood substitutes based on dextran perform mainly a volemic function, affecting mainly central hemodynamics. However, hypovolemia is also accompanied by peripheral circulatory disorders, which requires appropriate parallel correction of the rheological characteristics of the blood. The drug of low molecular weight fractions of dextran, rheopolyglucin, has such rheological activity.
Reopolyglucin (30,000-40,000 D; range of fractions 10,000-80,000 D) is a transparent, colorless, or slightly yellow solution of dextran. It contains low molecular weight dextran (100 g), sodium chloride (9 g), glucose (60 g; in the glucose preparation), water for injection (up to 1000 ml).
Rheopolyglucin can form a molecular layer on the surface cell membranes and vascular endothelium. In this regard, it increases the electronegativity of erythrocytes and platelets, which leads to a disaggregation effect, reduces the risk of intravascular thrombus formation and the development of disseminated intravascular coagulation syndrome, improves the rheological properties of blood and microcirculation and, ultimately, metabolism. The relative fineness of the drug determines high level COD and promotes the rapid movement of fluid into the vascular bed, due to which the BCC increases (or normalizes) due to an increase mainly in plasma volume (volemic coefficient of about 1.4). The hemodilution that develops accelerates and enhances the rheological effect, one of the manifestations of which is an increase in diuresis and accelerated excretion of toxic metabolites.
Indications for the use of rheopolyglucin are microcirculation disorders, regardless of etiological factor(“reversible” shock, burn injury in the acute period, sepsis, “shock” lung, “shock” kidney, etc.); tendency to hypercoagulation and thrombosis; thromboembolic complications; acute period myocardial infarction; intoxication, including acute exogenous poisoning, peritonitis, pancreatitis and others; condition of major surgical interventions.
Reopolyglucin infusions are relatively contraindicated in cases of severe overhydration accompanied by oliguria; with severe congestive circulatory failure; pronounced hemodilution (hematocrit less than 0.15 l/l); primary fibrinolysis; ongoing internal bleeding without arterial hypotension. The drug should be used very carefully either in case of chronic sepsis or latent purulent infection, since the rapid opening of the peripheral vascular bed can cause a large amount of toxins and vascular-active (vasodilator) substances to enter the bloodstream and cause severe collapse. To prevent such a complication, rheopolyglucin is infused 50-100 ml 3-4 times a day, slowly, up to 4 drops per minute.
Some foreign blood substitutes based on dextran, in particular macrodex, reomacrodes(Sweden), plasmafusin, reofusin, plasmateril, infucol(Germany), judextraven(France), dextran-70(USA), intradex(Great Britain), dextran-polfa(Poland), chemodex, rheodex(Yugoslavia) and others, differ from domestic rheopolyglucin in the electrolyte composition of the salt base and a narrower molecular weight distribution of fractions.
C olloidal blood substitutions for animals of animal origin include gelatin preparations. Gelatin is a high-molecular, water-soluble substance that is not a complete protein, since it does not contain the limiting amino acids tryptophan and tyrosine. However, unlike other proteins, it does not have specificity, and therefore is convenient as a blood substitute.
Gelatinol is an 8% solution of partially hydrolyzed edible gelatin obtained from collagen-containing tissues of cattle. This is a transparent, amber-colored liquid that foams easily and contains peptides of various molecular weights.
The mechanism of action of gelatinol is determined by its colloidal properties, similar to those of blood plasma, and is manifested when administered intravenously by an increase in blood volume due to an increase in intravascular volume. However, this increase is small (volemic coefficient about 0.5) and short-lived. Therefore, gelatinol should be used as an addition to anti-shock infusion therapy, especially when it is necessary to provide long-term drip infusions.
Indications for the use of gelatinol are dictated by its mechanism of action and properties. First of all, this drug is used in the complex treatment of hypovolemia of any origin (shock, blood loss, multiple trauma, etc.), purulent-septic syndrome (in particular, intoxication in acute surgical diseases of the abdominal organs), controlled hemodelution (including the use of artificial circulation and to fill the apparatus).
There are no absolute contraindications for gelatinol. It is relatively contraindicated in acute and chronic nephritis.
Gelatinol is well tolerated, non-toxic, non-anaphylactic; does not have a negative effect on the blood coagulation system, does not accumulate in the body; combines with all blood substitutes in any ratio.
BLOOD REPLACEMENT OF BLOOD ORIGIN, created on the basis of modified (ethoxylated) starch (OES).
In terms of hemodynamic action, OEC preparations are not inferior to dextrans (polyglucin and its analogues), and in terms of colloid-osmotic properties they are similar to albumin. They are non-toxic, do not have a negative effect on blood coagulation, and do not cause allergic reactions. Amylopectin starch is similar in structure to glycogen and is capable of being broken down by amylopectic enzymes (blood amylase) to release unsubstituted glucose. Therefore, the molecular weight of this drug does not play a significant role in determining its properties, as is the case with dextrans.
Volekam– a domestic drug created on the basis of OEC. Its MM is 170,000 D, DS0.55 – 0.7, i.e. it is similar or close to Japanese. A technological process for obtaining this drug has been developed and clinical trials have been carried out.
Group 2 – detoxification blood substitutes– is a low molecular weight colloid of polyvinylpyrrolidone and polyvinyl alcohol. By stimulating diuresis and possessing rheological activity, they bind circulating toxins and quickly remove them from the bloodstream.
Hemodez(12600 ± 2700 D) – 6% solution of low molecular weight polyvinylpyrrolidone (PVP-N), which contains polyvinylpyrrolidone-N (60 g), sodium chloride (5.5 g), potassium (0.42 g), potassium (0 .5 g) and magnesium (0.005 g), sodium bicarbonate (0.23 g), water for injection (up to 1000 ml). It is a clear, slightly yellowish, odorless liquid.
The high complex-forming ability of polyvinylpyrrolidone determines the effect of binding and neutralizing toxins with hemodez (especially in childhood intestinal infections, burns), and the redeployment of albumin into the bloodstream, blood thinning and a moderate increase in plasma volume are the rheological, diuretic and disaggregant effects of the drug. It should, however, be emphasized that these effects appear only when there are no significant disturbances in central and peripheral hemodynamics. Like other colloids, hemodez is polydisperse and contains particles with a molecular weight from 10,000 to 45,000 D, and determines the rate of its elimination and the time of onset of the clinical effect, which manifests itself already in the first minutes of administration.
Hemodez infusions are indicated for thermal burns(in the first 3-5 days), acute intestinal obstruction (both in preparation for surgery and in the early postoperative period, destructive forms appendicitis, cholecystitis, pancreatitis, sepsis, peritonitis, liver failure, i.e., intoxication syndrome, including acute endogenous poisoning.
Cardiopulmonary decompensation, hemorrhagic stroke, acute nephritis, and bronchial asthma are considered absolute contraindications for the use of hemodesis. You should also very carefully prescribe hemodesis to patients with pulmonary pathology, unstable hemodynamics, and acute renal failure.
Hemodez is administered intravenously, slowly (up to 40-60 drops/min), in daily dose 5 ml/kg. More often, the daily dose is administered in two doses with an interval of 12 hours. Hemodez infusions are carried out daily throughout the entire period of toxemia. However, increasing the dose or duration of use of the drug does not provide a corresponding increase in effect.
Neohemodesis(8000±2000 D) is a 6% solution that has the basic properties of hemodesis. However, neohemodesis is less reactogenic, causes a more pronounced rheological effect, and stimulates diuresis more strongly. It is indicated for the same pathological conditions and in the same doses as hemodez.
Polidez(10000±2000 D) is a 3% solution of PVA-N in a 0.9% sodium chloride solution. This is a transparent, colorless (or slightly yellowish), slightly opalescent solution. The drug is non-toxic, non-antigenic, pyrogen-free, and is quickly excreted from the body by the kidneys (up to 60-80% in the first day).
The mechanism of action of polydesis is determined primarily by its adsorption properties, which ensure the binding of toxins in the vascular bed. Due to its low molecular weight, polydesis is well filtered by the kidneys, stimulating diuresis and renal blood flow. The rheological effect of polydesis is manifested by the disaggregation of blood cells in the microcirculation vessels.
Polydesis is indicated for the same pathological conditions and in the same doses as hemodesis. The drug is administered intravenously at a rate of no more than 20-40 drops/min. The daily dose for adults is 400 ml.
Group 3 – drugs for parenteral nutrition.
Parenteral nutrition (PN) is understood as a special form of intravenous therapeutic nutrition that provides correction of impaired metabolism (under various pathological conditions) using special infusion solutions that can actively include metabolic processes body.
There are total and partial parenteral nutrition.
Total parenteral nutrition(PPP) consists of intravenous administration of all nutritional components in quantities and ratios that most closely correspond to the needs of the body at the moment. Such nutrition is usually necessary during complete and prolonged fasting.
Partial parenteral nutrition(NPP) is most often a complement to enteral therapy (natural or tube), if the latter does not meet the patient’s needs (due to a significant increase in energy costs, low-calorie diet, poor absorption of food, etc.).
Carbohydrates for parenteral nutrition it is used in the form of monosaccharides (glucose, fructose, invertose) and alcohols (dihydric - ethanol, butanediol and propanediol; polyhydric - sorbitol, xylitol).
Glucose is the main energetic component of both enteral and parenteral nutrition. Most often, 10 and 20% solutions are used, somewhat less often – 40 and 50%. Glucose is well absorbed by the body, actively participating in metabolic processes in all tissues and organs with the formation of 4.1 kcal of energy for each gram of metabolized substance.
Insulin plays a large role in glucose metabolism, since it helps to “economize” this process. Therefore, when infusions of large amounts of glucose, parallel fractional (preferably subcutaneous) administration of insulin is necessary at the rate of 1 unit per 3-5 g of glucose.
Fructose, Unlike glucose, it is an insulin-independent monosaccharide. In the body, it is absorbed faster and more completely than glucose (by about 20-25%), and therefore its use can be an alternative option for patients diabetes mellitus, with pancreatic necrosis or resection of the pancreas. If liver function is not impaired and small intestine(its metabolic transformations mainly occur here), it is a complete substitute for glucose. In the body, up to 50–70% of fructose is converted into glucose, 20–25% into lactate. When completely utilized, the energy value of fructose is similar to that of glucose. It is most advisable to use 10 and 20% fructose solutions.
Ethanol. With uniform (constant throughout the day) intravenous administration of ethanol at a dose of 1 g/kg/day and a fully functioning liver, no toxic side effects are observed. The absorption of alcohol is also facilitated by the simultaneous use of other carbohydrates. Ethanol infusions are contraindicated in cases of irreversible shock, liver damage, or cerebral coma.
Fats are a high-calorie component of parenteral nutrition. When 1 g of neutral fat is oxidized, 9.3 kcal of energy is released.
Intralipid(Sweden) developed in the 60s. and is a 10 and 20% soybean oil emulsion. This is a milky liquid. It contains essential fatty acids (linoleic acid - 54.3% and linolenic acid 7.8%), lecithin egg yolk(emulsifier; 12 g/l) and osmotic corrector glycerol (25 g/l).
Intralipid infusions are indicated in all cases where it is necessary to provide a high caloric intake while limiting the total volume of infusion. It is also used as a necessary supplement to carbohydrate nutrition. The use of Intralipid is contraindicated in patients in terminal condition and shock, in the early postoperative and post-resuscitation periods, with hyperlipemia, diabetic coma, nephrotic syndrome, liver failure, thromboembolic complications (to prevent the development of the latter, heparin is introduced into the bottle - 1 unit per 1 ml of solution).
A group of fat emulsions prepared from cottonseed oil include: lipofundin 10% (Finland), lipomule 15% (USA), lipofundin 15% (Germany), And lipiphysan 15% (France).
Nitrogenous preparations. Protein hydrolysates are solutions containing a mixture of amino acids and simple peptides. They are obtained by acid or enzymatic hydrolysis of blood proteins in cattle and humans. Due to the development of more advanced preparations for protein nutrition, the importance of protein hydrolysates has currently decreased.
Casein hydrolyzate– acid hydrolyzate of casein – a transparent liquid of straw-yellow or yellowish-cinnamon color with a specific odor. Contains 39.3 g/l amino acids (19.6 g/l - essential); 3.7 – 19.7 g/l of simple peptides; 5.5 g/l sodium chloride; 0.4 g/l potassium chloride and 0.005 g/l magnesium chloride; 7-9.5 g/l of total nitrogen (amine – 35–45%). To improve the absorption of amino acids, it is recommended to simultaneously administer potassium (up to 4 mmol/g nitrogen), glucose (or fructose), and B vitamins.
Hydrolysin-2– improved acid hydrolyzate of cattle blood proteins with a small amount of peptides and humic substances.
Amino acid mixtures They are superior in biological properties to protein hydrolysates and are practically displacing them from use.
Polyamine– 8% solution of a mixture of crystalline amino acids in L-form and 5% sorbitol (amino acids – 80 g, sorbitol – 50 g, pyrogen-free water – up to 1 l). It is administered intravenously at a rate of 25-35 drops/min in an average daily dose of up to 1000 ml, daily during the entire administration of the drug, depending on the amount of protein loss. Polyamine is well tolerated. The inclusion of sorbitol in its composition significantly improves the absorption of amino acids. In terms of clinical and biological properties, polyamine is not inferior to the best and foreign drugs similar functional purpose.
Vamin "Vitrum"(Sweden) – 7% solution of a mixture of crystalline L-amino acids with fructose (100 g/l) and electrolytes (sodium – 50 mmol/l; potassium – 20 mmol/l; calcium – 2.5 mmol/l; magnesium – 1.5 mmol/l; chlorine – 55 mmol/l); osmolarity 1275 mOsm/L; calorie content (fructose) is about 400 kcal/l. Total amino acids – 70 g/l (essential – 29 g/l); amine nitrogen – 7.7 g/l.
Macro- and microelements– no less important components of parenteral nutrition.
Basic M a c r o e m e n ts– potassium, sodium, calcium, magnesium, chlorine – are included in many preparations for PN. In order to correct the electrolyte balance, the content of electrolytes in plasma and erythrocytes is constantly determined, followed by the use of appropriate mono- or polyelectrolyte solutions.
Microelements - phosphorus, iron, copper, iodine, zinc, fluorine, chromium, manganese, cobalt and others - carry a significant load in the implementation of various metabolic processes in the body and, under physiological conditions, are supplied in sufficient quantities with food.
Group 4 – correctors of water-electrolyte metabolism and acid-base balance.
Isotonic sodium chloride solution(saline solution) was the first solution used as a blood substitute, including for acute blood loss. The idea of the “physiologicality” of a 0.85–0.9% sodium chloride solution was based on its isosmoticity with respect to blood plasma. It was soon proven that the “physiological” solution is not physiological at all, because it is not isoionic with blood plasma. It penetrates through vascular membranes and quickly (within 20–40 minutes) leaves the vascular bed, causing tissue hydration and acidosis. Despite this, it is used in almost all infusion therapy programs as independent drug and as the basis of some complex solutions.
The drug is indicated for various violations body water balance ( intravenous administration at a dose of up to 2 l/day). When injecting large volumes of solution (more than 2 l), tissue hyperhydration may occur, which leads to edema syndrome. In such cases, it is recommended to use diuretics. The rate of infusion (drip, stream) is dictated by the specific clinical situation. However, drip infusions are preferable.
Ringer's solution(sodium chloride – 8 g, potassium chloride – 0.3 g, calcium chloride – 0.33 g, water for injection – up to 1 l; or sodium – 140 mmol/l, potassium – 4, calcium – 6, chlorine – 150 mmol/l). The osmolarity of Ringer's solution is 300 mOsm/L.
Ringer's solution is compatible with all blood substitutes and blood. The duration of its circulation in the bloodstream is 30 – 60 minutes. Its salt composition is closer to blood plasma than isotonic sodium chloride solution, and, therefore, more physiological.
Modifications of Ringer's solution are drugs acesol(contains 2 g sodium acetate, 5 g sodium chloride, 1 g potassium chloride, up to 1 liter of water for injection) and xlosol(contains 3.6 g sodium acetate, 4.75 g sodium chloride, 1.75 g potassium chloride, up to 1 liter of water for injection).
The group of water-electrolyte balance correctors also includes drugs that have an osmodiuretic effect. These are primarily solutions of mannitol and sorbitol.
Mannitol is a solution of hexahydric alcohol mannitol. And metabolic processes are involved insignificantly. Actively excreted by the kidneys. With a jet intravenous infusion of 0.5 - 1.5 g/kg body weight, 15% mannitol has a powerful diuretic effect due to an increase in the osmotic pressure of blood plasma and a decrease in water reabsorption (solutions below 5% concentration do not have a diuretic effect). Mannitol is indicated (if the filtration capacity of the kidneys is preserved) for therapy acute edema brain in case of injury, in post-resuscitation and post-hypoxic periods, during operations on the skull, during detoxification of the body by forcing diuresis, with complications caused by transfusion of incompatible blood, etc.
The drug is contraindicated in anuria, severe cardiopulmonary failure with anasarca.
Sorbitol is a hexahydric alcohol sorbitol. Sorbitol administered intravenously at a rate of more than 120 drops/min (in a stream) has an osmodiuretic effect, but in this case it is also involved in metabolism. Isotonic (6%) sorbitol has a disaggregant effect and thereby improves microcirculation and tissue perfusion.
Electrolytes-correctors of acid-correcting hormones are used mainly for metabolic acidosis and alkalosis.
Bicarbonate (hydrocarbonate) depending on the level of electrolytes in plasma, it is used in the form of sodium or potassium salt in molar concentration (8.4% and 10%, respectively). Its effect manifests itself 10–15 minutes after the start of administration.
Bicarbonate is contraindicated in case of impaired CO 2 excretion (hypoventilation).
Sodium lactate It is quite possible to replace bicarbonate if the patient has a predominant aerobic metabolic pathway, when lactate is oxidized to release energy. In case of severe circulatory failure, especially with impaired microcirculation, sodium lactate is contraindicated.
Group 5 – oxygen carriers– drugs that can perform the function of oxygen transport without the participation of blood cells.
The positive effect of using blood substitutes in the treatment of blood loss and shock is determined by their volumetric and rheological properties, which determine the necessary oxygen transport even with a small volume of red blood cells. However, with a significant loss of red blood cell volume by the body, a sharp decrease in the oxygen capacity of the blood cannot be compensated only hemodynamically. The hypoxemia that inevitably arises in this case requires appropriate correction with blood infusions, which is not desirable or not always feasible. Therefore, the search for new blood substitutes capable of reversibly binding and transporting oxygen is very important and is being carried out all over the world. The first work in this area was aimed at creating a drug based on hemoglobin. It is known that in the structure of an erythrocyte, the oxygen transport function is performed by hemoglobin, and the species-specific function is performed by proteins of the erythrocyte stroma. Freed from the protein stroma, pure chemical hemoglobin is capable of reversibly binding oxygen, is not an antigen, and does not have nephrotoxicity. In the form of a drug eryghem it has been successfully used experimentally and clinically for the treatment of blood loss, anemia, coagulation disorders, etc. However, it is characterized by a small oxygen capacity (3.3 - 4 vol%) and a short circulation duration (several hours). In this regard, another drug was subsequently developed - modified polymerized hemoglobin, the oxygen capacity of which reached 10%. It was used to create polyhemoglobinalbumin(complex of hemoglobin with albumin), which has quite satisfactory hemodynamic and gas transport properties. However, in recent years, work on improving these drugs has been suspended, because the direction of creating artificial oxygen carriers based on fully fluorinated hydrocarbon compounds - fluorocarbons (FCS) - has turned out to be more promising.
TO fluorocarbons These are chemically inert substances, all of whose hydrogen atoms are replaced by fluorine atoms. Fluorocarbons are insoluble in water, and in order to make them functionally suitable, finely dispersed emulsions are prepared from them using surfactants (Pluronic, etc.) as the aqueous phase. PPS are capable of dissolving gases, in particular oxygen, 40–50% per unit volume, which is almost 3 times more than water and blood plasma. And an emulsified preparation containing 20% organofluorine compound can dissolve up to 10 vol% oxygen. The concentration of oxygen physically dissolved in PPS linearly depends on the concentration of the former in the emulsion, and the ability to transfer oxygen is directly proportional to its concentration in the surrounding air.
Companies and research centers in Japan, the USA, France and England are most actively developing new blood substitutes - oxygen carriers based on PPS emulsion. The polycyclic hydrocarbons perfluorodecalin (PFD) and perfluorotripropylamine (PFTPA) are most often used as the main components.
Created in 1973 in Japan by Green Cross Corporation, the drug “ Fluosol-DA20» is a 20% PPS emulsion of the following composition (in g per 100 ml of emulsion): perfluorodecalin - 14 g, perfluoropropylamine - 6 g, Pluronic F-68 - 2.7 g, phospholipids - 0.4 g, glycerin - 0.8 g , sodium chloride – 0.034 g, potassium chloride – 0.02 g, magnesium chloride – 0.028 g, sodium bicarbonate – 0.21 g, glucose – 0.18 g, hydroxyethyl starch – 3 g.
In order for the emulsion to have an oxygen capacity comparable to that of whole blood, it must be saturated pure oxygen, and this is not always desirable, nor is it feasible in non-clinical settings.
It should be noted that the emulsion during internal infusion causes a number of side effects: tachycardia, difficulty breathing, arterial hypotension, etc. In addition, it accumulates in the liver and spleen. Despite this, the emulsion still found use in cardiac surgery, including operations on a “dry” heart; in the treatment of anaerobic infections and acute carbon monoxide poisoning; with acute massive blood loss and shock. It is used for the preservation and transportation of isolated organs, to provide ventilated liquid oxygenation, etc.
By 1985, drugs similar to foyuosol-DA were created perftoran And perfucol.
All drugs belonging to the first generation oxygen carriers have common disadvantages: low oxygen capacity, the need for freezing for long-term storage; long retention in the body with a relatively short time of circulation in the bloodstream, reactogenicity. All this currently supports the widespread clinical use of these drugs and forces us to actively continue work on their improvement and creation of new ones.
To group 6 – complex blood substitutes– refer to semi-functional blood substitutes that simultaneously or sequentially provide two or more effects (for example, volemic and detoxification, anti-shock and nutritional, etc.). These are the ones listed above rheopolyglucin(anti-shock, rheological and detoxification effects), gelatinol(anti-shock, detoxification and nutritional effect), as well as specially created reogluman and sormanthol.
Reogluman is a 10% solution of dextran with a molecular weight of 40,000 ± 10,000 D in a 0.9% solution of sodium chloride and 5% mannitol. It is a transparent, colorless, odorless liquid; pH 4 – 6.5; relative viscosity 7. The properties of the ingredients included in this drug (reopolyglucin and mannitol) determine its functional purpose: correction of microcirculation disorders, reduction of intravascular aggregation, detoxification. Regluman infusions are carried out for the prevention and treatment of post-resuscitation illness. It is indicated for injuries, burns, and extensive surgical interventions. It is also used in vascular and plastic surgery to reduce thrombosis and improve local circulation; in the treatment of centralization of blood circulation in acute blood loss; in the complex treatment of intoxication syndrome; in the treatment of hepatic-renal failure with preserved filtration capacity of the kidneys; in the treatment of post-transfusion complications, etc. This drug is relatively contraindicated in cases of severe hemodilution and hemorrhagic diathesis.
Sormanthol provides a diuretic effect (due to the action of mannitol included in its composition) and serves as an energy substrate (due to the properties of sorbitol). It is a sweetish white powder, highly soluble in any aqueous solution. Available in 500 ml bottles containing 15 g of sorbitol, 15 g of mannitol, 0.04 g of sodium sulfacyl and 1.7 g of sodium chloride. Before use, diluted in 200 ml of solvent (15% solution) and used for conditions accompanied by fluid retention in the body, but with preserved filtration function of the kidneys; as a detoxifying agent, including for liver failure; with intravascular hemolysis, etc. In addition, sormantol accelerates the restoration of intestinal motility in postoperative period, increases bile secretion, helps reduce intracranial pressure. It is contraindicated in case of cardiac decompensation and impaired filtration capacity of the kidneys.
The mechanism of action of sormanthol is based on the hypertonicity of the solution, which provides a rapid osmodiuretic effect, especially in the first hours after administration.
Ecrinol- a bifunctional blood substitute created on the basis of modified amylopectin starch. Combines hemodynamic and detoxification properties.
Aminodesis has an active detoxifying effect and helps correct protein metabolism.
Polyvisolin created on the basis of polyvinyl alcohol with a molecular weight of 10,000 D. It has a pronounced hemodynamic and detoxification effect.
Polyoxidine created on the basis of polyethylene glycol with a molecular weight of 20,000 D. It has an anti-shock, rheological and detoxification effect.
