What is detoxification and how is it carried out?

Detoxication is the neutralization of toxic substances of exogenous and endogenous origin, the most important mechanism for maintaining chemical resistance, which is a whole complex of biochemical and biophysical reactions provided by the functional interaction of several physiological systems, including the immune system of the blood, the monooxygenase system of the liver and secretory systems of the excretory organs (gastrointestinal tract, lungs , kidneys, skin).

Direct choice of ways of detoxification depends on the physical and chemical properties of the toxicant (molecular weight, water and fat solubility, ionization, etc.).

It should be noted that immune detoxification is a relatively late evolutionary acquisition, characteristic only of vertebrates. His ability to "adjust" to fight a foreign agent penetrating the body makes immune defense a universal weapon against virtually all possible compounds with a large molecular mass. Most systems specialized in the processing of protein substances with a lower molecular weight are called conjugate, they are localized in the liver, although they are more or less present in other organs.

The effect of toxins on the body depends ultimately on their damaging effect and the severity of detoxification mechanisms. In modern works devoted to the problem of traumatic shock, it is shown that immediately after the trauma, circulating immune complexes appear in the blood of the affected. This fact confirms the presence of antigenic invasion in a shockogenic trauma and indicates that the antigen-antibody combination occurs quickly after injury. Immune protection against high molecular toxin antigen consists in the production of antibodies - immunoglobulins, which have the ability to bind to the antigen of a toxin and form a nontoxic complex. Thus, in this case, too, we are talking about a peculiar conjugation reaction. However, its surprising feature is that in the body in response to the appearance of the antigen, only the clone of immunoglobulins begins to be synthesized, which is completely identical to the antigen and can provide its selective binding. Synthesis of this immunoglobulin occurs in B-lymphocytes with the participation of macrophages and populations of T-lymphocytes.

The further fate of the immune complex lies in the fact that it is gradually lysed by a complement system consisting of a cascade of proteolytic enzymes. The resulting decomposition products can be toxic, and this immediately manifests itself as intoxication if the immune processes go too fast. The reaction of antigen binding to the formation of immune complexes and their subsequent cleavage by the complement system can occur on the membrane surface of many cells, and the recognition function, as recent studies have shown, belongs not only to lymphoid cells, but to many others that secrete proteins that possess the properties of immunoglobulins. Such cells include hepatocytes, spleen dendritic cells, erythrocytes, fibroblasts, etc.

Glycoprotein - fibronectin has a branched structure, and this provides the possibility of its attachment to the antigen. The resulting structure promotes faster attachment of the antigen to the phagocytizing leukocyte and its neutralization. This function of fibronectin and some other similar proteins is called opsonizing, and the bangs themselves are called opsonins. The dependence between the decrease in the level of fibronectin of blood in trauma and the frequency of development of complications in the post-shock period was established.

The bodies that perform detoxification

The immune system detoxifies high-molecular xenobiotics such as polymers, bacterial toxicants, enzymes and other substances by their specific detoxification and microsomal biotransformation by the type of antigen-antibody reactions. In addition, proteins and blood cells transport to the liver and the temporary deposition (adsorption) of many toxicants, thereby protecting the receptors of toxicity from their effects. The immune system consists of central organs (bone marrow, thymus gland), lymphoid formations (spleen, lymph nodes) and immunocompetent blood cells (lymphocytes, macrophages, etc.) that play a major role in the identification and biotransformation of toxicants.

The protective function of the spleen includes blood filtration, phagocytosis and the formation of antibodies. It is a natural sorption system of the body, which reduces the content of pathogenic circulating immune complexes and medium-molecular toxicants in the blood.

The detoxification role of the liver consists in the biotransformation of mainly medium-molecular xenobiotics and endogenous toxicants with hydrophobic properties by including them in oxidative, reducing, hydrolytic and other reactions catalyzed by the corresponding enzymes.

The next stage of biotransformation is conjugation (formation of paired ethers) with glucuronic, sulfuric, acetic acids, glutathione and amino acids, which leads to an increase in the polarity and water solubility of toxicants, which facilitate their removal by the kidneys. In this case, anti-peroxide protection of liver cells and the immune system, carried out by special enzymes-antioxidants (tocopherol, superoxide dismutase, etc.) is of great importance.

The detoxification capabilities of the kidneys are directly related to their active participation in maintaining the chemical homeostasis of the body by biotransformation of xenobiotics and endogenous toxicants and their subsequent excretion in the urine. For example, tubular peptidases continuously undergo hydrolytic decomposition of low molecular weight proteins, including peptide-like hormones (vasopressin, ACTH, angiotensin, gastrin, etc.), thereby returning amino acids used in synthetic processes to the bloodstream. Of particular importance is the ability to excrete water-soluble medium-molecular peptides with urine in the development of endotoxicosis, on the other hand, a prolonged increase in their pool can contribute to damage to the tubular epithelium and the development of nephropathy.

The detoxifying function of the skin is determined by the work of sweat glands secreting up to 1000 ml of sweat containing urea, creatinine, heavy metal salts, many organic substances, including low and medium molecular weight, per day. In addition, with the secretion of sebaceous glands, fatty acids are removed - products of intestinal fermentation and many medicinal substances (salicylates, phenazone, etc.).

The lungs perform their detoxification function by acting as a biological filter that monitors the level of biologically active substances in the blood (bradykinin, prostaglandins, serotonin, noradrenaline, etc.), which, if their concentration increases, can become endogenous toxicants. The presence of microsomal oxidases in the lungs makes it possible to oxidize many hydrophobic substances of medium molecular weight, which confirms the determination of a larger amount in venous blood than in arterial blood. It has a number of detoxification functions, providing regulation of lipid metabolism and elimination of high-polar compounds and various conjugates hydrolyzed under the influence of digestive tract enzymes and intestinal microflora. Some of them can be reabsorbed into the blood and again enter the liver for the next round of conjugation and excretion (enterohepatic circulation). The provision of detoxification of the intestine is significantly hampered by oral poisoning, when various toxicants are deposited in it, including endogenous ones, which are resorbed by the concentration gradient and become the main source of toxicosis.

Thus, the normal activity of the general system of natural detoxification (chemical homeostasis) maintains a sufficiently reliable cleansing of the organism from exogenous and endogenous toxic substances when their concentration in the blood does not exceed a certain threshold level. Otherwise, there is accumulation of toxicants at toxicity receptors with the development of a clinical picture of toxicosis. This danger is significantly increased in the presence of premorbid disorders from the main organs of natural detoxification (kidney, liver, immune system), as well as in elderly and senile patients. In all these cases, there is a need for additional support or stimulation of the entire system of natural detoxification to ensure correction of the chemical composition of the internal environment of the body.

Detoxification, that is, detoxification, consists of a series of steps

In the first stage of treatment, toxins are exposed to oxidase enzymes, resulting in the formation of reactive groups of OH-, COOH, SH ~, or H ", which make them" convenient "for further binding. The enzymes that perform this biotransformation belong to the group of oxidases with shifted functions, and among them the main role is played by the hemo-containing enzymatic protein cytochrome P-450. It is synthesized by hepatocytes in the ribosomes of the rough membranes of the endoplasmic reticulum. Biotransformation of the toxin proceeds step by step with the formation of the substrate-enzyme complex AN • Fe3 +, consisting of a toxic substance (AN) and cytochrome P-450 (Fe3 +) in an oxidized form. Then the complex AN • Fe3 + is reduced by one electron to AN • Fe2 + and adds oxygen, forming a triple complex of AN • Fe2 +, consisting of a substrate, an enzyme and oxygen. The further reduction of the ternary complex by the second electron leads to the formation of two unstable compounds with the reduced and oxidized form of cytochrome P-450: AH • Fe2 + 02 ~ = AH • Fe3 + 02 ~, which decompose into hydroxylated toxin, water and the initial oxidized form of P-450 , which again proves to be capable of reacting with other molecules of the substrate. However, the cytochrome substrate, the oxygen complex, AH • Fe2 + O2 +, even before the addition of the second electron, can pass into the oxidized form of AN • Fe3 + 02 ~ with the release of the superoxide anion 02 as a by-product with a toxic effect. It is possible that such a discharge of the superoxide radical is a cost to the detoxification mechanisms, for example, due to hypoxia. In any case, the formation of the superoxide anion 02 in the oxidation of cytochrome P-450 is reliably established.

The second stage of detoxification of the toxin consists in carrying out the conjugation reaction with various substances, which leads to the formation of non-toxic compounds released from the body in one way or another. Conjugation reactions are named after the substance acting as a conjugate. Usually the following types of these reactions are considered: glucuronide, sulfate, with glutathione, with glutamine, with amino acids, methylation, acetylation. The listed variants of conjugation reactions ensure the clearance and removal of most compounds with toxic effects from the body.

The most universal is the conjugation with glucuronic acid, which is a repeating monomer in the composition of hyaluronic acid. The latter is an important component of connective tissue and therefore is present in all organs. Naturally, the same applies to glucuronic acid. The potential of this conjugation reaction is determined by the catabolism of glucose along the secondary pathway, the result of which is the formation of glucuronic acid.

Compared to glycolysis or the citric acid cycle, the mass of glucose used for the secondary pathway is small, but the product of this route, glucuronic acid, is a vital detoxification agent. Typical participants for detoxification with glucuronic acid are phenols and their derivatives that form a bond with the first carbon atom. This leads to the synthesis of harmless to the body of phenol glucosiduranides released to the outside. Glucuronide conjugation is topical for exo- and endotoxins having the properties of lipotropic substances.

Less effective is sulphate conjugation, which is considered to be more ancient in evolutionary terms. It is provided by 3-phosphoadenosine-5-phosphodisulfate, formed as a result of the interaction of ATP and sulfate. Sulfate conjugation of toxins is sometimes seen as duplicating with respect to other methods of conjugation and is included when they are depleted. Inadequate efficiency of sulfate conjugation also consists in the fact that during the binding of toxins, substances that retain toxic properties can be formed. Sulfate binding occurs in the liver, kidneys, intestines and brain.

The three following types of conjugation reaction with glutathione, glutamine, and amino acids are based on a general mechanism for the use of reactive groups.

The conjugation scheme with glutathione was studied more than others. This tripeptide, consisting of glutamic acid, cysteine and glycine, participates in the conjugation reaction of more than 40 different compounds of exo- and endogenous origin. The reaction proceeds in three or four stages with successive cleavage from the resulting conjugate of glutamic acid and glycine. The remaining complex, consisting of xenobiotic and cysteine, can already in this form be excreted from the body. However, more often there is a fourth stage in which cysteine is acetylated with an amino group and mercapturic acid is formed, which is excreted in the bile. Glutathione is a component of another important reaction, leading to the neutralization of peroxides that are formed endogenously and constitute an additional source of intoxication. The reaction proceeds according to the scheme: glutathione peroxidase 2GluH + H202 2Glu + 2H20 (reduced (oxidized glutathione) glutathione) and is catabolized by the enzyme glutathione peroxidase, an interesting feature of which is that it contains selenium in the active site.

In the process of amino acid conjugation, glycine, glutamine and taurine are most often involved in humans, although other amino acids are also possible. The last two of the conjugation reaction types under consideration are related to the transfer to a xenobiotic of one of the radicals: methyl or acetyl. The reactions are respectively catalyzed by methyl or acetyltransferases contained in the liver, lungs, spleen, adrenal glands and some other organs.

An example is the reaction of ammonia conjugation, which is formed in high amounts during trauma as the final product of protein breakdown. In the brain, this is an extremely toxic compound that can cause coma in the event of excess formation, binds to glutamate and turns into a nontoxic glutamine that is transported to the liver and there turns into another nontoxic compound - urea. In muscles, excess ammonia binds to ketoglutarate and in the form of alanine is also transferred to the liver followed by the formation of urea, which is excreted in the urine. Thus, the blood urea level indicates, on the one hand, the intensity of protein catabolism, and on the other hand, the filtration capacity of the kidneys.

As already noted, during the biotransformation of xenobiotics, a highly toxic radical (O2) is formed. It is established that up to 80% of the total amount of superoxide anions with the participation of the superoxide dismutase (SOD) enzyme passes into hydrogen peroxide (H202), the toxicity of which is much less than that of the superoxide anion (02 ~). The remaining 20% of superoxide anions are included in some physiological processes, in particular, they interact with polyunsaturated fatty acids, forming lipid peroxides that are active in muscle contraction processes, regulate the permeability of biological membranes, etc. However, in the case of redundancy, H202 and lipid peroxides may be harmful, creating a threat of toxic damage to the body with active forms of oxygen. To support homeostasis, a powerful series of molecular mechanisms is activated, and, first of all, the SOD enzyme, which limits the rate of the conversion of O2 to active forms of oxygen. With a reduced level of SOD, spontaneous dissolution of 02 takes place with the formation of singlet oxygen and H202, with the interaction of which 02 causes the formation of even more active hydroxyl radicals:

202 '+ 2H + -> 02' + H2O2;

02 "+ H202 -> 02 + 2 OH + OH.

SOD catalyzes both direct and reverse reactions and is an extremely active enzyme, and the activity value is programmed genetically. The remaining part of H2O2 participates in metabolic reactions in the cytosol and in the mitochondria. Catalase is the second line of anti-peroxide protection of the body. It is found in the liver, kidneys, muscles, brain, spleen, bone marrow, lungs, erythrocytes. This enzyme decomposes hydrogen peroxide to water and oxygen.

Enzyme protective systems "quench" free radicals with the help of protons (Ho). Maintenance of homeostasis with the action of active oxygen forms includes non-enzyme biochemical systems. These include endogenous antioxidants - fat-soluble vitamins of group A (beta-carotenoids), E (a-tocopherol).

Some role in anti-radical protection is played by endogenous metabolites-amino acids (cysteine, methionine, histidine, arginine), urea, choline, reduced glutathione, sterols, unsaturated fatty acids.

Enzyme and non-enzyme systems of antioxidant protection in the body are interrelated and coordinated. In many pathological processes, including in the case of a shock injury, there is an "overload" of the molecular mechanisms responsible for maintaining homeostasis, which leads to an increase in intoxication with irreversible consequences.

[1], [2]

Methods of intraocorporal detoxification

See also: Intracorporal and extracorporeal detoxification

Wound membrane dialysis according to EA Selezov

Well wound membranous dialysis according to EA Selezov (1975) proved to be successful. The main component of the method is an elastic bag - a dialyzer from a semipermeable membrane with a pore size of 60-100 μm. The bag is filled with dialyzing drug solution, which includes (at the rate of 1 liter of distilled water), g: calcium gluconate 1.08; glucose 1.0; potassium chloride 0.375; magnesium sulfate 0.06; sodium bicarbonate 2.52; acid sodium phosphate 0.15; sodium hydrophosphate 0.046; sodium chloride 6.4; vitamin C 12 mg; CO, is dissolved to a pH of 7.32-7.45.

To increase the oncotic pressure and accelerate the outflow of the contents of the wound, dextran (polyglucin) with a molecular weight of 7000 daltons in the amount of 60 grams is added to the solution. It is also possible to add antibiotics to which the wound microflora is sensitive, at a dose equivalent to 1 kg of the patient's weight, antiseptics (solution of dioxidine 10 ml), analgesics (1% solution of novocaine - 10 ml). The leading and outgoing tubes built into the bag allow the dialysis device to be used in flow mode. The average flow rate of the solution should be 2-5 ml / min. After this preparation, the bag is placed in the wound in such a way that its entire cavity is filled with it. The dialysis solution is changed once every 3-5 days, and the membrane dialysis is continued until the appearance of granulations. Membrane dialysis provides active removal from the wound of exudate containing toxins. So, for example, 1 g of dry dextran binds and holds 20-26 ml of tissue fluid; A 5% dextran solution attracts liquid with a force of up to 238 mm Hg. Art.

Catheterization of the regional artery

To deliver the maximum dose of antibiotics to the affected area, if necessary, catheterization of the regional artery is used. To do this, a Seldinger puncture leads to a catheter in the central artery in the appropriate artery, through which antibiotics are subsequently administered. Two methods of administration are used: one-time or by continuous drip infusion. The latter is accomplished by lifting the vessel with an antiseptic solution to a height higher than the blood pressure level or using a blood perfusion pump.

The approximate composition of the solution administered intraarterially is as follows: saline, amino acids, antibiotics (thienam, kefzol, gentamicin, etc.), papaverine, vitamins, etc.

Duration of infusion may be 3-5 days. The catheter needs careful monitoring because of the possibility of blood loss. The risk of thrombosis with the correct procedure is minimal. 14.7.3.

[3], [4]

Forced diuresis

Toxic substances, which are formed in large numbers during trauma and lead to the development of intoxication, are released into the blood and lymph. The main task of detoxification therapy is to use methods that can extract toxins from plasma and lymph. This is achieved by introducing large volumes of fluids into the bloodstream, which "dilute" plasma toxins and are excreted from the body with the kidneys. For this, low-molecular solutions of crystalloids (saline, 5% glucose solution, etc.) are used. Spend up to 7 liters per day, combining this with the introduction of diuretics (furosemide 40-60 mg). In the composition of infusion media for conducting forced diuresis, it is necessary to include high-molecular compounds that are capable of binding toxins. The best of them were protein preparations of human blood (5, 10 or 20% solution of albumin and 5% protein). Synthetic polymers such as rheopolyglucin, hemodez, polyvisaline and others are also used.

Solutions of low molecular weight compounds are applied with a detoxification purpose only when the patient has sufficient diuresis (above 50 ml / h) and a good reaction to diuretic drugs.

[5], [6], [7], [8]

Possible complications

The most frequent and severe is the overflow of the vascular bed with liquid, which can lead to pulmonary edema. Clinically, this is manifested by dyspnea, an increase in the number of wet wheezing in the lungs audible at a distance, the appearance of foamy sputum. An earlier objective evidence of hypertransfusion during forced diuresis is an increase in the level of central venous pressure (CVP). Increase the level of CVP above 15 cm of water. Art. (the normal value of CVP is 5-10 cm H2O) serves as a signal to stop or significantly reduce the rate of fluid administration and increase the dose of the diuretic. It should be borne in mind that a high level of CVP can be in patients with cardiovascular pathology in heart failure.

When carrying out forced diuresis, one should remember about the possibility of developing hypokalemia. Therefore, strict biochemical monitoring of the level of electrolytes in plasma and red blood cells is necessary. There are absolute contraindications for conducting forced diuresis - oligo- or anuria, despite the use of diuretics.

Antibacterial therapy

The pathogenetic method of combating intoxication during a shock injury is antibacterial therapy. Early and sufficient concentration of broad-spectrum antibiotics is required, with several mutually compatible antibiotics. The most appropriate simultaneous use of two groups of antibiotics - aminoglycosides and cephalosporins in combination with drugs that act on anaerobic infection, such as metrogil.

Open bone fractures and wounds are an absolute indication for prescribing antibiotics that are administered intravenously or intra-arterially. An approximate scheme of intravenous administration: gentamicin 80 mg 3 times a day, kefzol 1.0 g up to 4 times a day, metrogyl 500 mg (100 ml) for 20 minutes dropwise 2 times a day. Correction of antibiotic therapy and the appointment of other antibiotics are performed in the days following the receipt of the results of the tests and the sensitivity of the bacterial flora to antibiotics.

[9], [10], [11], [12], [13], [14], [15], [16]

Detoxification with inhibitors

This direction of detoxification therapy is widely used in exogenous poisoning. In endogenous toxicoses, including those developing as a result of a shock injury, there are only attempts to use such approaches. This is explained by the fact that information on toxins formed during traumatic shock is far from complete, not to mention the fact that the structure and properties of most substances participating in the development of intoxication remain unknown. Therefore, one can not seriously expect to receive active inhibitors of practical importance.

However, clinical practice in this area has some experience. Previously, others in the treatment of traumatic shock began to use antihistamines such as diphenhydramine in accordance with the provisions of the histamine theory of shock.

Recommendations on the use of antihistamines in traumatic shock are contained in many guidelines. In particular, it is recommended to use diphenhydramine in the form of injections 1-2% solution 2-3 times a day to 2 ml. Despite the long-term experience of using histamine antagonists, their clinical effect is not strictly proven, except for allergic reactions or experimental histamine shock. More promising was the idea of using antiproteolytic enzymes. If we proceed from the assumption that protein catabolism is the main supplier of toxins with different molecular weights and that in the case of shock it is always increased, it becomes clear the possibility of a favorable effect from the use of agents that suppress proteolysis.

This issue was studied by a German researcher (Schneider, V., 1976), who applied the proteolysis inhibitor aprotinin to victims with traumatic shock and received a positive result.

Proteolytic inhibitors are necessary for all victims with extensive pogranozhennye wounds. Immediately after delivery to the hospital, such an injured person is injected intravenously with a drip solution (20 000 ATPE per 300 ml of physiological solution). Its introduction is repeated 2-3 times a day.

In the practice of treating patients with shock, naloxone is used - an inhibitor of endogenous opiates. Recommendations for its use are based on the work of scientists who have shown that naloxone blocks such adverse effects of opiate and opioid drugs, like cardiodepressor and bradykinin action, while retaining their useful analgesic effect. Experience in the clinical use of one of the drugs naloxone narcanti (DuPont, Germany) showed that its administration at a dose of 0.04 mg / kg body weight was accompanied by some anti-shock effect, manifested in a significant increase in systolic blood pressure, systolic and minute heart volume, minute volume of respiration, an increase in arterio-venous difference in p02, and oxygen consumption.

Other authors did not find the antishock effect of these drugs. In particular, scientists have shown that even the maximum doses of morphine do not have a negative effect on the course of hemorrhagic shock. They believe that the beneficial effect of naloxone can not be related to the suppression of endogenous opiate activity, since the amount of endogenous opiates produced was significantly less than the morphine dose that they administered to the animals.

As already reported, one of the factors of intoxication are perekionnye compounds, formed in the body in shock. The use of their inhibitors has so far been implemented only partially in the course of experimental studies. The general name for these drugs is scavengers (cleaners). These include SOD, catalase, peroxidase, allopurinol, manpitol and a number of others. Practical value has mannitol, which in the form of a 5-30% solution is used as a means to stimulate diuresis. To these its properties should be added an antioxidant effect, which, quite possibly, is one of the reasons for its favorable anti-shock effect. The strongest "inhibitors" of bacterial intoxication, which always accompanies infectious complications in a shockogenic trauma, can be considered antibiotics, as previously reported.

In the works of A. Ya. Kulberg (1986) it was shown that the shock is naturally accompanied by the invasion of the circulation of a number of intestinal bacteria in the form of lipopolysaccharides of a certain structure. It has been established that the administration of antilipopolysaccharide serum neutralizes this source of intoxication.

Scientists have established the amino acid sequence of toxin of toxic shock syndrome produced by Staphylococcus aureus, which is a protein with a molecular weight of 24,000. Thus, the basis for obtaining a highly specific antiserum for one of the antigens of the most common microbial staphylococcus aureus in man has been created.

However, detoxification therapy for traumatic shock associated with the use of inhibitors has not yet reached perfection. The practical results obtained are not so impressive as to cause great satisfaction. However, the prospect of "pure" toxin inhibition in shock without side adverse effects is quite possible against the backdrop of advances in biochemistry and immunology.

[17], [18], [19], [20], [21], [22],

Methods of extracorporeal detoxification

The detoxification methods described above can be referred to as endogenous or intracorporeal. They are based on the use of drugs acting inside the body, and are associated either with stimulation of the detoxification and excretory functions of the body, or with the use of substances sorbing toxins, or with the use of inhibitors of toxic substances formed in the body.

In recent years, the extracorporeal detoxification methods, which are based on the principle of artificial extraction of one or another environment of an organism containing toxins, are increasingly developed and used. An example of this is the method of hemosorption, which is the passage of the patient's blood through activated charcoal and its return to the body.

The technique of plasmapheresis or simple cannulation of the lymphatic ducts for the purpose of removing lymph involves the removal of toxic blood plasma or lymph with the replacement of protein losses by intravenous administration of protein preparations (solutions of albumin, protein or plasma). Sometimes a combination of extracorporeal detoxification methods is used, which includes simultaneously conducted procedures of plasmapheresis and sorption of toxins on the coals.

In 1986, a completely special method of extracorporeal detoxification was introduced into clinical practice, which involves passing the patient's blood through the spleen taken from the pig. This method can be attributed to extracorporeal biosorption. At the same time, the spleen works not only as a biosorbent, since it also has a bactericidal ability, it injects various biologically active substances into the blood perfused through it and influences the immunological status of the organism.

The peculiarity of using extracorporeal detoxification methods in victims with traumatic shock is the need to take into account the traumatism and scale of the proposed procedure. And if patients with normal hemodynamic status tolerate extracorporeal detoxification procedures are usually good, then patients with traumatic shock may have adverse effects of the hemodynamic plan in the form of an increase in heart rate and a decrease in systemic arterial pressure, which depend on the amount of extracorporeal blood volume, duration of perfusion and the amount of removed plasma or lymph. It should be considered a rule that the extracorporeal volume of blood does not exceed 200 ml.

Hemosorption

Among methods of extracorporeal detoxification, hemosorption (HS) is one of the most common and is used in an experiment since 1948 in the clinic since 1958. Under hemosorption is understood the excretion of toxic substances from the blood by passing it through the sorbent. The vast majority of sorbents are solids and are divided into two large groups: 1 - neutral sorbents and 2 - ion-exchange sorbents. In clinical practice, neutral sorbents, represented in the form of activated carbons of different brands (AP-3, SKT-6A, SKI, SUTS, etc.) were most widely used. Characteristic properties of coals of any brand is the ability to adsorb a wide range of various compounds contained in the blood, including not only toxic, but also useful. In particular, oxygen is extracted from the flowing blood and, thereby, its oxygenation is significantly reduced. The most advanced brands of coals extract from blood up to 30% of platelets and thus create the conditions for bleeding, especially when it is considered that the HS is carried out with the mandatory introduction into the blood of a patient with heparin in order to prevent coagulation. These properties of coals contain a real threat in the event that they are used to assist victims with traumatic shock. A special feature of the coal sorbent is that, when perfused, fine particles of 3 to 35 μm in size are removed into the blood and then deposited in the spleen, kidneys and brain tissue, which can also be considered an undesirable effect in treating patients who are in critical condition. At the same time, there are no real ways to prevent the "dusting" of sorbents and the flow of small particles into the bloodstream by means of filters, since the use of filters with pores less than 20 μm will impede the passage of the cellular part of the blood. The proposal to cover the sorbent with a polymer film partly solves this problem, but at the same time, the adsorption capacity of coals significantly decreases, and "dusting" is not completely prevented. The listed features of coal sorbents limit the use of HS on coal for the purpose of detoxification in victims with traumatic shock. The area of its use is limited to patients with a marked intoxication syndrome against the background of preserved hemodynamics. Usually these are patients with isolated crushing of limbs, accompanied by the development of a syndrome. HS in victims with traumatic shock is used with the use of a veno-venous shunt and providing a constant blood flow with a perfusion pump. The duration and rate of hemoperfusion through the sorbent is determined by the patient's response to the procedure and, as a rule, lasts for 40-60 minutes. In the case of undesirable reactions (arterial hypotension, unrestrained chills, resumption of bleeding from wounds, etc.), the procedure is terminated. In the case of a shock trauma, GS contributes to the clearance of medium molecules (30.8%), creatinine (15.4%), urea (18.5%). Simultaneously, the number of red blood cells decreases by 8.2%, the number of leukocytes by 3%, hemoglobin by 9%, and the leukocyte intoxication index by 39%.

Plasmapheresis

Plasmapheresis is a procedure that ensures the separation of blood into the cellular part and plasma. It is established that plasma is the main carrier of toxicity, and for this reason its removal or purification gives the effect of detoxification. There are two ways of separating the plasma from the blood: centrifugation and filtration. Earlier, there were methods of gravitational blood separation, which are not only used, but also continue to improve. The main disadvantage of centrifuge methods, consisting in the need to take relatively large amounts of blood, is partially eliminated by using devices that provide continuous extracorporeal blood flow and constant centrifugation. However, the volume of filling devices for centrifugal plasmapheresis remains relatively high and ranges between 250-400 ml, which is unsafe for victims with traumatic shock. More promising is the method of membrane or filtration plasmapheresis, in which the separation of blood occurs through the use of finely porous filters. Modern devices equipped with such filters have a small filling volume that does not exceed 100 ml and provide the possibility of blood separation according to the size of the particles contained in it up to large molecules. For the purpose of plasmapheresis, membranes having a maximum pore size of 0.2-0.6 μm are used. This ensures the sifting of most of the medium and large molecules, which, according to modern concepts, are the main carriers of the toxic properties of the blood.

Clinical experience shows that patients with traumatic shock usually tolerate membrane plasmapheresis under the condition of withdrawal of a moderate volume of plasma (not exceeding 1-1.5 liters) with simultaneous adequate plasma substitution. For the procedure of membrane plasmapheresis under sterile conditions, an installation is assembled from standard blood transfusion systems, the connection of which to the patient is made by the type of veno-venous shunt. Usually for this purpose, catheters introduced by Seldinger into two main veins (subclavian, femoral) are used. It is necessary one-step intravenous administration of heparin at the rate of 250 units. For 1 kg of weight of the patient and the introduction of 5 thousand units. Heparin per 400 ml of physiological solution drip into the entrance to the apparatus. The optimal perfusion rate is chosen empirically and is usually in the range of 50-100 ml / min. The pressure drop in front of the inlet and outlet of the plasma filter should not exceed 100 mm Hg. Art. To avoid hemolysis. Under these conditions of conducting plasmapheresis for 1-1.5 hours, about 1 liter of plasma can be obtained, which should be replaced with an adequate amount of protein preparations. The resulting plasmapheresis plasma is usually released, although it is possible to purify it with the help of coals for HS and return to the patient's vascular bed. However, this variant of plasmapheresis in the treatment of victims with traumatic shock is not universally recognized. The clinical effect of plasmapheresis often occurs almost immediately after removal of the plasma. First of all, this manifests itself in the clarification of consciousness. The patient begins to come into contact, talk. As a rule, there is a decrease in the level of CM, creatinine, bilirubin. The duration of the effect depends on the severity of intoxication. When you resume signs of intoxication, you need to re-conduct plasmapheresis, the number of sessions of which has no limitations. However, in practical conditions, it is conducted no more than once a day.

Lymphosorption

Lymphosorption has emerged as a method of detoxification, which allows to avoid trauma of blood elements, inevitable with HS and occurring with plasmapheresis. The procedure of lymphosorption begins with the drainage of the lymphatic duct, usually the thoracic duct. This operation is quite difficult and not always successful. Sometimes it does not succeed in connection with the "loose" type of the structure of the thoracic duct. The lymph is collected in a sterile vial with the addition of 5 thousand units. Heparin for every 500 ml. The rate of lymph drainage depends on several causes, including hemodynamic status and anatomical features. Lymph outflow lasts for 2-4 days, while the total amount of collected lymph varies from 2 to 8 liters. Then the collected lymph is sorbed at the rate of 1 bottle of SKN coals with a capacity of 350 ml per 2 l of lymph. After that, antibiotics (1 million units of penicillin) are added to the sorbed lymph of 500 ml, and it is reinfused to the patient by intravenous drip.

The method of lymphosorption due to duration and complexity in technical terms, as well as significant protein losses, has limited application in victims with mechanical trauma.

Extracorporeal connection of the donor spleen

A special place among the methods of detoxification is the extracorporeal connection of the donor spleen (ECDC). This method combines the effects of hemosorption and immunostimulation. In addition, it is the least traumatic of all methods of extracorporeal cleansing of the blood, since it is a biosorption. Conducting EKPDS is accompanied by the least trauma of blood, which depends on the mode of operation of the roller pump. In this case, there is no loss of blood cells (in particular, platelets), which inevitably occurs with HS on coal. In contrast to HS on coal, plasmapheresis and lymphosorption, there is no protein loss in ECDPDS. All these properties make this procedure the least traumatic of all methods of extracorporeal detoxification, and therefore it can be used in patients in critical condition.

Pork spleen is taken immediately after the slaughter of the animal. Cut off the spleen at the time of removal of the complex of internal organs in compliance with the rules of aseptic (sterile scissors and gloves) and place in a sterile cuvette with a solution of furatsilina 1: 5000 and antibiotic (kanamycin 1.0 or penicillin 1 million units). A total of 800 ml of the solution is spent on washing the spleen. Vessel crossing points are treated with alcohol. The intersected splenic vessels are ligated with silk, the main vessels are catheterized with polyethylene tubes of different diameters: the splenic artery is catheter with an internal diameter of 1.2 mm, the splenic vein is 2.5 mm. Through the catheterized splenic artery, the body is constantly rinsed with sterile saline solution with addition of 5 thousand units per 400 ml of solution. Heparin and 1 million units. Penicillin. Perfusion rate is 60 drops per minute in the transfusion system.

The perfused spleen is delivered to a hospital in a special sterile shipping container. During transport and in the hospital, the perfusion of the spleen continues until the fluid emerging from the spleen becomes transparent. Approximately 1 liter of washing solution is used for this. Extracorporeal connection is performed more often by the type of veno-venous shunt. Blood perfusion is performed using a roller pump at a rate of 50-100 ml / min, the duration of the procedure is about 1 hour on average.

With EKSPDS sometimes there are technical complications associated with poor perfusion of individual sections of the spleen. They can occur either due to an inadequate dose of heparin administered at the entrance to the spleen, or as a result of improper placement of catheters in the vessels. A sign of these complications is a decrease in the rate of blood flowing from the spleen and an increase in the volume of the whole organ or its individual parts. The most serious complication is the thrombosis of the spleen vessels, which, as a rule, is irreversible, but these complications are noted, mainly, only in the process of mastering the EKSPDS technique.

[23], [24], [25], [26], [27], [28]