What is detoxification and how is it done?

Detoxification 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 the excretory systems of the excretory organs (gastrointestinal tract, lungs, kidneys, skin).

The direct choice of detoxification routes depends on the physicochemical 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. Its ability to "adapt" to combat a foreign agent that has penetrated the body makes immune defense a universal weapon against virtually all possible compounds with a large molecular weight. Most systems specialized in processing protein substances with a lower molecular weight are called conjugate; they are localized in the liver, although they are also present to varying degrees in other organs.

The effect of toxins on the body ultimately depends on their damaging effect and the severity of detoxification mechanisms. Modern studies on the problem of traumatic shock have shown that circulating immune complexes appear in the blood of victims immediately after the injury. This fact confirms the presence of antigen invasion in shockogenic injury and indicates that the antigen meets the antibody fairly quickly after the injury. Immune protection from a high-molecular toxin - an antigen - consists of producing antibodies - immunoglobulins that have the ability to bind to the toxin antigen and form a non-toxic complex. Thus, in this case we are also talking about a kind of conjugation reaction. However, its amazing feature is that in response to the appearance of an antigen, the body begins to synthesize only that clone of immunoglobulins that is completely identical to the antigen and can provide its selective binding. The synthesis of this immunoglobulin occurs in B-lymphocytes with the participation of macrophages and T-lymphocyte populations.

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

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

Organs 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 many toxicants to the liver and temporarily deposit (adsorb) them, thereby protecting toxicity receptors 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.), which play a major role in the identification and biotransformation of toxicants.

The protective function of the spleen includes blood filtration, phagocytosis and antibody formation. It is the body's natural sorption system, reducing the content of pathogenic circulating immune complexes and medium-molecular toxicants in the blood.

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

The next stage of biotransformation is conjugation (formation of paired esters) with glucuronic, sulfuric, acetic acids, glutathione and amino acids, leading to an increase in the polarity and water solubility of toxicants, facilitating their excretion by the kidneys. In this case, antiperoxide protection of liver cells and the immune system, carried out by special antioxidant enzymes (tocopherol, superoxide dismutase, etc.), is of great importance.

The detoxification capabilities of the kidneys are directly related to their active participation in maintaining the body's chemical homeostasis by biotransforming xenobiotics and endogenous toxicants with their subsequent excretion with urine. For example, with the help of tubular peptidases, low-molecular proteins are constantly hydrolytically decomposed, including peptide hormones (vasopressin, ACTH, angiotensin, gastrin, etc.), thereby returning amino acids to the blood, which are subsequently used in synthetic processes. Of particular importance is the ability to excrete water-soluble medium-molecular peptides with urine during the development of endotoxicosis; on the other hand, a long-term 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, which secrete up to 1000 ml of sweat per day, containing urea, creatinine, salts of heavy metals, many organic substances, including low and medium molecular weight. In addition, fatty acids - products of intestinal fermentation and many medicinal substances (salicylates, phenazone, etc.) are removed with the secretion of the sebaceous glands.

The lungs perform their detoxification function, acting as a biological filter that controls the blood level of biologically active substances (bradykinin, prostaglandins, serotonin, norepinephrine, etc.), which, when their concentration increases, can become endogenous toxicants. The presence of a complex of microsomal oxidases in the lungs allows for the oxidation of many hydrophobic substances of medium molecular weight, which is confirmed by the determination of their greater quantity in venous blood compared to arterial blood. The gastrointestinal tract has a number of detoxification functions, ensuring the regulation of lipid metabolism and the removal of highly polar compounds and various conjugates entering with bile, which are capable of hydrolyzing under the influence of enzymes in the digestive tract 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). Ensuring the detoxification function of the intestine is significantly complicated by oral poisoning, when various toxicants are deposited in it, including endogenous ones, which are resorbed along 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 fairly reliable cleansing of the body from exogenous and endogenous toxic substances when their concentration in the blood does not exceed a certain threshold level. Otherwise, toxicants accumulate on the receptors of toxicity with the development of a clinical picture of toxicosis. This danger increases significantly in the presence of premorbid disorders of the main organs of natural detoxification (kidneys, 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 the correction of the chemical composition of the internal environment of the body.

Neutralization of toxins, that is, detoxification, consists of a number of stages

At the first stage of processing, toxins are exposed to the action of oxidase enzymes, as a result of which they acquire reactive groups 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 displaced functions, and among them the main role is played by the heme-containing enzyme protein cytochrome P-450. It is synthesized by hepatocytes in the ribosomes of the rough membranes of the endoplasmic reticulum. Biotransformation of the toxin occurs in stages with the initial formation of a substrate-enzyme complex AH • Fe3+, consisting of a toxic substance (AH) and cytochrome P-450 (Fe3+) in oxidized form. Then the AH • Fe3+ complex is reduced by one electron to AH • Fe2+ and attaches oxygen, forming a ternary complex AH • Fe2+, consisting of a substrate, enzyme and oxygen. Further reduction of the ternary complex by the second electron results in the formation of two unstable compounds with the reduced and oxidized forms of cytochrome P-450: AH • Fe2 + 02~ = AH • Fe3 + 02~, which decompose into the hydroxylated toxin, water and the original oxidized form of P-450, which again proves capable of reacting with other substrate molecules. However, the cytochrome-oxygen complex substrate AH • Fe2 + 02+ can, even before the addition of the second electron, transform into the oxide form AH • Fe3 + 02~ with the release of the superoxide anion 02 as a by-product with a toxic effect. It is possible that such a release of the superoxide radical is a cost of detoxification mechanisms, for example, due to hypoxia. In any case, the formation of the superoxide anion 02 during the oxidation of cytochrome P-450 has been reliably established.

The second stage of toxin neutralization consists of a conjugation reaction with various substances, which leads to the formation of non-toxic compounds that are excreted from the body in one way or another. Conjugation reactions are named after the substance that acts as a conjugate. The following types of these reactions are usually considered: glucuronide, sulfate, with glutathione, with glutamine, with amino acids, methylation, acetylation. The listed variants of conjugation reactions ensure the neutralization and excretion of most compounds with toxic action from the body.

The most universal is considered to be conjugation with glucuronic acid, which is included in the form of 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, which results in 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 pathway, glucuronic acid, is a vital means of detoxification. Typical participants for detoxification with glucuronic acid are phenols and their derivatives, which form a bond with the first carbon atom. This leads to the synthesis of harmless phenol glucosiduranides, which are released to the outside. Glucuronide conjugation is relevant for exo- and endotoxins, which have the properties of lipotropic substances.

Less effective is sulfate 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 considered as a duplicate in relation to other methods of conjugation and is included when they are exhausted. The insufficient efficiency of sulfate conjugation also consists in the fact that in the process of binding toxins, substances can be formed that retain toxic properties. Sulfate binding occurs in the liver, kidneys, intestines and brain.

The following three types of conjugation reactions with glutathione, glutamine and amino acids are based on a common mechanism of using reactive groups.

The conjugation scheme with glutathione has been 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 occurs in three or four stages with successive cleavage of glutamic acid and glycine from the resulting conjugate. The remaining complex, consisting of a xenobiotic and cysteine, can already be excreted from the body in this form. However, the fourth stage occurs more often, in which cysteine is acetylated at the amino group and mercapturic acid is formed, which is excreted with bile. Glutathione is a component of another important reaction leading to the neutralization of peroxides formed endogenously and representing an additional source of intoxication. The reaction proceeds according to the scheme: glutathione peroxidase 2GluH + H2O2 2Glu + 2H2O (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 center.

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

An example is the reaction of ammonia conjugation, which is formed in increased quantities during trauma as the end product of protein breakdown. In the brain, this extremely toxic compound, which can cause coma if it is formed in excess, binds with glutamate and turns into non-toxic glutamine, which is transported to the liver and there turns into another non-toxic compound - urea. In the muscles, excess ammonia binds with ketoglutarate and is also transported to the liver in the form of alanine, with the subsequent formation of urea, which is excreted in the urine. Thus, the level of urea in the blood indicates, on the one hand, the intensity of protein catabolism, and on the other, the filtration capacity of the kidneys.

As already noted, the process of biotransformation of xenobiotics involves the formation of a highly toxic radical (O2). It has been established that up to 80% of the total amount of superoxide anions, with the participation of the enzyme superoxide dismutase (SOD), is converted into hydrogen peroxide (H2O2), the toxicity of which is significantly less than that of the superoxide anion (02~). The remaining 20% of superoxide anions are involved in some physiological processes, in particular, they interact with polyunsaturated fatty acids, forming lipid peroxides, which are active in muscle contraction processes, regulate the permeability of biological membranes, etc. However, in the case of excess H2O2, lipid peroxides can be harmful, creating a threat of toxic damage to the body by active forms of oxygen. To maintain homeostasis, a powerful series of molecular mechanisms are activated, primarily the enzyme SOD, which limits the rate of the cycle of conversion of 02~ into active forms of oxygen. At reduced levels of SOD, spontaneous dismutation of O2 occurs with the formation of singlet oxygen and H2O2, with which O2 interacts to form even more active hydroxyl radicals:

202' + 2Н+ -> 02' + Н202;

02” + H202 -> 02 + 2 OH + OH.

SOD catalyzes both the forward and reverse reactions and is an extremely active enzyme, with the activity level being genetically programmed. The remaining H2O2 participates in metabolic reactions in the cytosol and mitochondria. Catalase is the body's second line of antiperoxide defense. It is found in the liver, kidneys, muscles, brain, spleen, bone marrow, lungs, and erythrocytes. This enzyme breaks down hydrogen peroxide into water and oxygen.

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

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

Enzymatic and non-enzymatic antioxidant protection systems in the body are interconnected and coordinated. In many pathological processes, including shock-induced trauma, there is an "overload" of the molecular mechanisms responsible for maintaining homeostasis, which leads to increased intoxication with irreversible consequences.

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Intracorporeal detoxification methods

Read also: Intracorporeal and extracorporeal detoxification

Wound membrane dialysis according to E. A. Selezov

Wound membrane dialysis according to E. A. Selezov (1975) has proven itself well. The main component of the method is an elastic bag - a dialyzer made of a semipermeable membrane with a pore size of 60 - 100 μm. The bag is filled with a dialysis medicinal solution, which includes (based on 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; sodium acid phosphate 0.15; sodium hydrogen phosphate 0.046; sodium chloride 6.4; vitamin C 12 mg; CO, dissolved to pH 7.32-7.45.

In order to increase the oncotic pressure and accelerate the outflow of the wound contents, dextran (polyglucin) with a molecular weight of 7000 daltons in an amount of 60 g is added to the solution. Here you can also add antibiotics to which the wound microflora is sensitive, in a dose equivalent to 1 kg of the patient's weight, antiseptics (dioxidine solution 10 ml), analgesics (1% novocaine solution - 10 ml). The inlet and outlet tubes mounted in the bag make it possible to use the dialysis device in a flow mode. The average flow rate of the solution should be 2-5 ml / min. After the specified preparation, the bag is placed in the wound so that its entire cavity is filled with it. The dialysate solution is changed once every 3-5 days, and membrane dialysis continues until granulation appears. Membrane dialysis provides active removal of exudate containing toxins from the wound. For example, 1 g of dry dextran binds and holds 20-26 ml of tissue fluid; a 5% dextran solution attracts fluid with a force of up to 238 mm Hg.

Regional artery catheterization

In order to deliver the maximum dose of antibiotics to the affected area, regional artery catheterization is used in necessary cases. For this purpose, a catheter is inserted into the corresponding artery in the central direction using a Seldinger puncture, through which antibiotics are subsequently administered. Two methods of administration are used - one-time or by means of a long-term drip infusion. The latter is achieved by raising a vessel with an antiseptic solution to a height exceeding the arterial pressure level or using a blood perfusion pump.

The approximate composition of the solution administered intra-arterially is as follows: physiological solution, amino acids, antibiotics (tienam, kefzol, gentamicin, etc.), papaverine, vitamins, etc.

The duration of the infusion may be 3-5 days. The catheter must be carefully monitored due to the possibility of blood loss. The risk of thrombosis is minimal if the procedure is performed correctly. 14.7.3.

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Forced diuresis

Toxic substances, which are formed in large quantities 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 allow to extract toxins from plasma and lymph. This is achieved by introducing large volumes of liquids into the bloodstream, which "dilute" the plasma toxins and are excreted from the body along with them by the kidneys. Low-molecular solutions of crystalloids (saline, 5% glucose solution, etc.) are used for this. Up to 7 liters are consumed per day, combining this with the introduction of diuretics (furosemide 40-60 mg). The composition of infusion media for forced diuresis must include high-molecular compounds that are capable of binding toxins. The best of them turned out to be protein preparations of human blood (5, 10 or 20% albumin solution and 5% protein). Synthetic polymers are also used - rheopolyglucin, hemodez, polyvisalin, etc.

Solutions of low-molecular compounds are used for detoxification purposes only when the victim has sufficient diuresis (over 50 ml/h) and a good response to diuretics.

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Complications are possible

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

When performing forced diuresis, one should remember about the possibility of hypokalemia. Therefore, strict biochemical control over the level of electrolytes in the blood plasma and erythrocytes is necessary. There are absolute contraindications for performing forced diuresis - oligo- or anuria, despite the use of diuretics.

Antibacterial therapy

The pathogenetic method of combating intoxication in shock-producing trauma is antibacterial therapy. It is necessary to administer broad-spectrum antibiotics early and in sufficient concentration, using several mutually compatible antibiotics. The most appropriate is the simultaneous use of two groups of antibiotics - aminoglycosides and cephalosporins in combination with drugs that act on anaerobic infection, such as metrogyl.

Open bone fractures and wounds are an absolute indication for antibiotics administered intravenously or intra-arterially. Approximate intravenous administration scheme: 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 by drip 2 times a day. Correction of antibiotic therapy and prescription of other antibiotics are performed in the following days after receiving the test results and determining the sensitivity of bacterial flora to antibiotics.

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Detoxification using inhibitors

This direction of detoxification therapy is widely used in exogenous poisonings. In endogenous toxicoses, including those developing as a result of shockogenic trauma, there are only attempts to use such approaches. This is explained by the fact that information about toxins formed during traumatic shock is far from complete, not to mention the fact that the structure and properties of most substances involved in the development of intoxication remain unknown. Therefore, one cannot seriously count on obtaining active inhibitors of practical significance.

However, clinical practice in this area has some experience. Earlier than others, antihistamines such as diphenhydramine were used in the treatment of traumatic shock in accordance with the provisions of the histamine theory of shock.

Recommendations for 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 of a 1-2% solution 2-3 times a day up to 2 ml. Despite many years of experience in the use of histamine antagonists, their clinical effect has not been strictly proven, except for allergic reactions or experimental histamine shock. The idea of using antiproteolytic enzymes has proven to be more promising. If we proceed from the position that protein catabolism is the main supplier of toxins with different molecular weights and that it is always elevated in shock, then the possibility of a favorable effect from the use of agents that suppress proteolysis becomes clear.

This issue was studied by a German researcher (Schneider B., 1976), who used a proteolysis inhibitor, aprotinin, on victims with traumatic shock and obtained a positive result.

Proteolytic inhibitors are necessary for all victims with extensive crushed wounds. Immediately after delivery to the hospital, such victims are given intravenous drips of contrical (20,000 ATpE per 300 ml of physiological solution). Its administration is repeated 2-3 times a day.

In the practice of treating victims with shock, naloxone, an inhibitor of endogenous opiates, is used. 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 as cardiodepressor and bradykinin action, while maintaining their beneficial analgesic effect. Experience in the clinical use of one of the naloxone preparations, narcanti (DuPont, Germany), showed that its administration at a dose of 0.04 mg/kg of body weight was accompanied by some anti-shock effect, manifested in a reliable increase in systolic blood pressure, systolic and cardiac output, respiratory output, an increase in the arteriovenous difference in p02 and oxygen consumption.

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

As has already been reported, one of the intoxication factors are peroxide compounds formed in the body during shock. The use of their inhibitors has been implemented only partially so far, mainly in experimental studies. The general name of these drugs is scavengers (cleaners). They include SOD, catalase, peroxidase, allopurinol, manpitol and a number of others. Mannitol is of practical importance, which in the form of a 5-30% solution is used as a means of stimulating diuresis. To these properties should be added its antioxidant effect, which is quite possibly one of the reasons for its favorable anti-shock effect. The most powerful "inhibitors" of bacterial intoxication, which always accompanies infectious complications in shockogenic trauma, can be considered antibiotics, as reported earlier.

In the works of A. Ya. Kulberg (1986) it was shown that shock is regularly accompanied by the invasion of a number of intestinal bacteria into the circulation in the form of lipopolysaccharides of a certain structure. It was established that the introduction of anti-lipopolysaccharide serum neutralizes this source of intoxication.

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

However, detoxification therapy of 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" inhibition of toxins in shock without adverse side effects is quite probable against the background of advances in biochemistry and immunology.

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Extracorporeal Detoxification Methods

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

In recent years, methods of extracorporeal detoxification have been increasingly developed and used, based on the principle of artificially extracting a particular environment of the body containing toxins. An example of this is the hemosorption method, which involves passing the patient's blood through activated carbon and returning it to the body.

The plasmapheresis technique or simple cannulation of lymphatic ducts for the purpose of lymph extraction involves the removal of toxic blood plasma or lymph with the compensation of protein losses by intravenous administration of protein preparations (albumin, protein or plasma solutions). Sometimes a combination of extracorporeal detoxification methods is used, including simultaneously performed plasmapheresis procedures and sorption of toxins on 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 a pig. This method can be classified as extracorporeal biosorption. At the same time, the spleen works not only as a biosorbent, since it also has bactericidal properties, increting various biologically active substances into the blood perfused through it and influencing the immunological status of the body.

The peculiarity of using extracorporeal detoxification methods in victims with traumatic shock is the need to take into account the traumatic nature and scale of the proposed procedure. And if patients with normal hemodynamic status usually tolerate extracorporeal detoxification procedures well, then patients with traumatic shock may experience adverse hemodynamic consequences in the form of increased pulse rate and decreased systemic arterial pressure, which depend on the size of the extracorporeal blood volume, the duration of perfusion and the amount of plasma or lymph removed. It should be considered a rule that the extracorporeal blood volume does not exceed 200 ml.

Hemosorption

Among the methods of extracorporeal detoxification, hemosorption (HS) is one of the most common and has been used in experiments since 1948 and in clinics since 1958. Hemosorption is understood as the removal of toxic substances from the blood by passing it through a sorbent. The vast majority of sorbents are solid substances and are divided into two large groups: 1 - neutral sorbents and 2 - ion-exchange sorbents. In clinical practice, neutral sorbents are most widely used, presented in the form of activated carbons of various brands (AR-3, SKT-6A, SKI, SUTS, etc.). The characteristic properties of carbons of any brand are the ability to adsorb a wide range of various compounds contained in the blood, including not only toxic but also useful ones. In particular, oxygen is extracted from the flowing blood and thereby its oxygenation is significantly reduced. The most advanced brands of carbon extract up to 30% of platelets from the blood and thus create conditions for bleeding, especially considering that HS is performed with the mandatory introduction of heparin into the patient's blood to prevent blood clotting. These properties of carbons pose a real threat if they are used to provide assistance to victims with traumatic shock. A feature of carbon sorbent is that when it is perfused into the blood, small particles from 3 to 35 microns in size are removed and then deposited in the spleen, kidneys and brain tissue, which can also be considered an undesirable effect in the treatment of victims in critical condition. At the same time, there are no real ways to prevent the "dusting" of sorbents and the entry of small particles into the bloodstream using filters, since the use of filters with pores less than 20 microns will prevent the passage of the cellular part of the blood. The proposal to cover the sorbent with a polymer film partially solves this problem, but this significantly reduces the adsorption capacity of the coals, and "dusting" is not completely prevented. The listed features of carbon sorbents limit the use of GS on coals for the purpose of detoxification in victims with traumatic shock. The scope of its application is limited to patients with severe intoxication syndrome against the background of preserved hemodynamics. Usually, these are patients with isolated crushing injuries of the extremities, accompanied by the development of crush syndrome. GS in victims with traumatic shock is used using a veno-venous shunt and ensuring a constant blood flow using 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 40-60 minutes. In case of adverse reactions (arterial hypotension, intractable chills, resumption of bleeding from wounds, etc.), the procedure is stopped. In shock-induced trauma, GS promotes the clearance of medium molecules (30.8%), creatinine (15.4%), and urea (18.5%).At the same time, the number of erythrocytes decreases by 8.2%, leukocytes by 3%, hemoglobin by 9%, and the leukocyte intoxication index decreases by 39%.

Plasmapheresis

Plasmapheresis is a procedure that separates blood into the cellular part and plasma. It has been established that plasma is the main carrier of toxicity, and for this reason, its removal or purification provides a detoxifying effect. There are two methods for separating plasma from blood: centrifugation and filtration. Gravitational blood separation methods were the first to appear, and they are not only used, but also continue to be improved. The main disadvantage of centrifugal methods, which consists in the need to collect relatively large volumes of blood, is partly eliminated by using devices that provide continuous extracorporeal blood flow and constant centrifugation. However, the filling volume of devices for centrifugal plasmapheresis remains relatively high and fluctuates between 250-400 ml, which is unsafe for victims with traumatic shock. A more promising method is membrane or filtration plasmapheresis, in which blood is separated by using fine-pored filters. Modern devices equipped with such filters have a small filling volume, not exceeding 100 ml, and provide the ability to separate blood by the size of the particles contained in it, down to large molecules. For the purpose of plasmapheresis, membranes are used that have a maximum pore size of 0.2-0.6 μm. This ensures the sifting of most medium and large molecules, which, according to modern concepts, are the main carriers of the toxic properties of blood.

As clinical experience shows, patients with traumatic shock usually tolerate membrane plasmapheresis well, provided that a moderate volume of plasma is removed (not exceeding 1-1.5 l) with simultaneous adequate plasma substitution. To perform the membrane plasmapheresis procedure under sterile conditions, a unit is assembled from standard blood transfusion systems, which is connected to the patient as a veno-venous shunt. Usually, catheters inserted according to Seldinger into two main veins (subclavian, femoral) are used for this purpose. It is necessary to simultaneously administer intravenous heparin at a rate of 250 units per 1 kg of the patient's weight and administer 5 thousand units of heparin in 400 ml of physiological solution dropwise at the inlet of the unit. The optimal perfusion rate is selected empirically and is usually within 50-100 ml/min. The pressure difference before the plasma filter input and output should not exceed 100 mm Hg to avoid hemolysis. Under such conditions, plasmapheresis can produce about 1 liter of plasma in 1-1.5 hours, which should be replaced with an adequate amount of protein preparations. The plasma obtained as a result of plasmapheresis is usually discarded, although it can be purified with charcoal for GS and returned to the patient's vascular bed. However, this type of plasmapheresis is not generally accepted in the treatment of victims with traumatic shock. The clinical effect of plasmapheresis often occurs almost immediately after plasma removal. First of all, this is manifested in clearing up of consciousness. The patient begins to make contact, talk. As a rule, there is a decrease in the level of SM, creatinine, and bilirubin. The duration of the effect depends on the severity of intoxication. If signs of intoxication recur, plasmapheresis must be repeated, the number of sessions of which is not limited. However, in practical conditions it is carried out no more than once a day.

Lymphosorption

Lymphosorption emerged as a method of detoxification, allowing to avoid injury of formed elements of blood, inevitable in HS and occurring in plasmapheresis. The procedure of lymphosorption begins with drainage of the lymphatic duct, usually the thoracic one. This operation is quite difficult and not always successful. Sometimes it fails due to the "loose" type of structure of the thoracic duct. Lymph is collected in a sterile bottle with the addition of 5 thousand units of heparin for every 500 ml. The rate of lymph outflow depends on several factors, including the hemodynamic status and features of the anatomical structure. Lymphatic outflow continues for 2-4 days, while the total amount of collected lymph fluctuates from 2 to 8 liters. Then the collected lymph is subjected to sorption at the rate of 1 bottle of SKN brand coals with a capacity of 350 ml per 2 liters of lymph. After this, antibiotics (1 million units of penicillin) are added to the sorbed lymph (500 ml), and it is reinfused into the patient intravenously by drip.

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

Extracorporeal connection of donor spleen

Extracorporeal connection of donor spleen (ECDS) occupies a special place among detoxification methods. This method combines the effects of hemosorption and immunostimulation. In addition, it is the least traumatic of all methods of extracorporeal blood purification, since it is biosorption. ECDS is accompanied by the least trauma to the blood, which depends on the operating mode of the roller pump. At the same time, there is no loss of formed elements of the blood (in particular, platelets), which inevitably occurs with HS on coals. Unlike HS on coals, plasmapheresis and lymphosorption, there is no loss of protein with ECDS. All of the listed properties make this procedure the least traumatic of all methods of extracorporeal detoxification, and therefore it can be used in patients in critical condition.

The pig spleen is taken immediately after the slaughter of the animal. The spleen is cut off at the time of removal of the internal organs complex in compliance with the rules of asepsis (sterile scissors and gloves) and placed in a sterile cuvette with a solution of furacilin 1: 5000 and an antibiotic (kanamycin 1.0 or penicillin 1 million units). In total, about 800 ml of solution is spent on washing the spleen. The intersections of the vessels 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 with a catheter with an internal diameter of 1.2 mm, the splenic vein - 2.5 mm. Through the catheterized splenic artery, the organ is constantly washed with a sterile saline solution with the addition of 5 thousand units for every 400 ml of solution. heparin and 1 million units of penicillin. The perfusion rate is 60 drops per minute in the transfusion system.

The perfused spleen is delivered to the hospital in a special sterile transport container. During transportation and in the hospital, perfusion of the spleen continues until the fluid flowing out of the spleen becomes clear. This requires about 1 liter of washing solution. Extracorporeal connection is most often performed as a 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 on average about 1 hour.

During EKPDS, technical complications sometimes arise due to poor perfusion of individual areas of the spleen. They may occur either due to an insufficient dose of heparin administered at the entrance to the spleen, or as a result of incorrect placement of catheters in the vessels. A sign of these complications is a decrease in the speed of blood flowing from the spleen and an increase in the volume of the entire organ or its individual parts. The most serious complication is thrombosis of the spleen vessels, which, as a rule, is irreversible, but these complications are noted mainly only in the process of mastering the EKPDS technique.

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