Comprehensive detoxification of the body

Complex detoxification of the body in the toxicogenic stage of acute poisoning

Carrying out full detoxification in cases of mild and some moderate poisonings is not a difficult problem and is achievable by enhancing natural detoxification processes. For the treatment of severe poisonings, it is necessary, as a rule, to use artificial detoxification methods that allow purifying the blood and other body environments regardless of the degree of preservation of the natural detoxification function.

In the toxicogenic stage of poisoning, hemosorption is most successfully used. One of the main advantages of hemosorption when using non-selective sorbents is its high efficiency in relation to blood purification from a wide range of toxicants of exogenous and endogenous origin, which, due to their physicochemical characteristics (formation of large complexes with protein molecules, hydrophobicity), are insufficiently removed from the body by renal excretion or HD.

It is extremely important that hemosorption has non-specific therapeutic mechanisms associated with its corrective effect on homeostasis parameters. This is evidenced by the high clinical effectiveness of hemosorption, despite the fact that only 3 to 25% of the total amount of absorbed toxicant is removed from the blood during the operation. It is also noted that in cases where there are similar clearances, the half-life of toxicants (T1/2) during hemosorption is significantly (almost 2 times) shorter than during hemodialysis.

In general, as a result of the use of hemosorption, mortality in various types of acute poisoning is significantly reduced (by 7-30%).

However, the toxicokinetic characteristics of various detoxification methods dictate the need for their combined use with other highly effective detoxification measures.

One of such methods of detoxification is hemodialysis. Low-molecular toxicants are most intensively eliminated with this method, therefore HD is widely used in cases of poisoning with them, as well as in acute renal failure, allowing to cleanse the blood from urea, creatinine, and eliminate electrolyte disorders. Due to the insignificant negative effect of HD on hemodynamic parameters and formed elements of the blood, it can be carried out for a long time with perfusion of large volumes of blood in one session, which allows to achieve the elimination of large quantities of toxic metabolites from the body.

In some cases, such as poisoning with heavy metals and arsenic, methanol and ethylene glycol, hemodialysis is currently considered the most effective method of artificial detoxification of the body. Recently, for a more objective determination of indications for the use of hemodialysis or hemosorption, indicators of the volume of distribution of various toxicants are used, which are published in reference books. For example, if the volume of distribution is less than 1.0 l / kg, that is, the toxicant is distributed in the main vascular volume of the body's bioenvironment, then hemosorption is recommended, and if more than 1.0 l / kg, then it is better to use hemodialysis, which has the possibility of purifying a much larger volume of bioenvironments containing exogenous or endogenous toxicants.

Widespread introduction of such modifications as isolated blood UF, GF and HDF allow more effective purification of blood from medium-molecular toxicants and rapid correction of water-electrolyte and acid-base balance. In the latter case, the above advantages of filtration methods make it possible to classify them as resuscitation measures. One of the simple and popular methods of artificial detoxification is peritoneal dialysis. Using the peritoneum as a dialysis membrane with a large surface area makes it possible to remove larger molecules during PD, which significantly expands the range of toxic substances removed from the body.

Along with the problem of blood detoxification, it is extremely important to remove toxicants from the intestines in order to prevent their absorption into the blood and maintain their toxic concentrations in it. Intestinal lavage is used to eliminate the created depot, which allows to significantly reduce the duration of the toxicogenic stage and thereby improve the results of treatment. A valuable advantage of intestinal lavage, like PD, is the possibility of its implementation in case of hemodynamic disorders.

The combination of methods of enhancing natural detoxification and sorption-dialysis therapy with methods of enhancing biotransformation leads to an acceleration of the elimination of toxicants from the body by 1.5-3 times. For example, the rate of elimination of psychotropic toxicants increases significantly when combined with GHN. At the same time, the process of cleansing the body is accelerated due to the fact that the toxicant is intensively oxidized with the help of GHN, the infusions of which are carried out in the process of hemosorption.

As the severity of poisoning increases, detoxification technology involves the simultaneous use of several detoxification methods in accordance with the characteristics of the treatment mechanisms.

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Complex detoxification of the body in the somatogenic stage of poisoning

In acute poisoning, in addition to the specific toxic effect of the toxicant, non-specific disturbances of homeostasis also develop, which largely determine the general consequences of intoxication.

One of such disorders is endotoxicosis, which develops already in the first hours from the moment of poisoning and, regardless of the etiological factor, is accompanied by increasing disorders of the central nervous system, cardiovascular system and excretory organs due to the generalized process of accumulation of toxic metabolic products in the body, which is most clearly clinically noticeable in the somatogenic stage of poisoning after the removal of the main exogenous toxicant from the body.

At the same time, the impact of toxic concentrations of "biogenic" toxicants is no less dangerous than the previous influence of xenobiotics. The outcome of endogenous intoxication is gross microcirculation disorders, especially in the lungs, damage to organs and systems with the development of PON.

This pathology contributes to the development of life-threatening septic complications, especially pneumonia, as well as worsening hemodynamic disorders and deterioration of treatment results in general.

The most pronounced endogenous intoxication most often develops in acute poisoning with hepato- and nephrotoxic substances due to the disruption of the specific function of the liver and kidneys - the organs responsible for the inactivation and removal of toxic substances from the body. The accumulation of pathological metabolic products, active enzymes of intracellular organelles and tissue hormones in the body leads to the activation of LPO processes, the kallikrein-kinin system and intracellular hypoxia. Under conditions of increased vascular permeability and disrupted homeostasis, cytolysis develops, vital organs lose their specific function. Under the influence of endotoxins, the hormonal background changes, the immune system is suppressed, which is a predisposing factor for the development of infectious complications.

In acute exogenous poisoning, three degrees of nephropathy and hepatopathy are distinguished.

Nephropathy of the first degree is manifested by minor and short-term changes in the morphological composition of urine (erythrocyturia up to 20-60 in the field of vision, moderate proteinuria - from 0.033 to 0.33%, moderate leukocyturia, cylindruria). There is a slight decrease in the CF (76.6 ± 2.7 ml / min) and renal plasma flow (582.2 ± 13.6 ml / min) in the acute period of the disease with a rapid return to normal (within 1-2 weeks) with preserved concentration and urinary function of the kidneys.

Nephropathy of the II degree is manifested by oliguria, moderate azotemia, pronounced and long-term morphological changes in the composition of urine (up to 2-3 weeks). In this case, significant proteinuria, macrohematuria, cylindruria are noted, the presence of renal epithelial cells in the urine sediment, the KF decreases to 60+2.8 ml/min, tubular reabsorption to 98.2±0.1% and renal plasma flow to 468.7±20 ml/min.

Depending on the type of toxic substance that caused the poisoning, nephropathy is characterized by the development of acute pigment, hemoglobinuric, myoglobinuric or hydropic nephrosis.

Stage III nephropathy (SIN) is characterized by the suppression of all renal functions by oligoanuria or anuria, high azotemia, a sharp decrease or absence of CF, suppression or cessation of water reabsorption in the tubules. These changes are accompanied by a severe clinical picture caused by dysfunction of other organs and systems in the form of multiple organ pathology.

Hepatopathy of the 1st degree. During examination, no clinical signs of liver damage are revealed. Liver dysfunction is characterized by a moderate increase (by 1.5-2 times) in the activity of cytoplasmic enzymes with their normalization by the 7th-10th day, mild hyperbilirubinemia - no more than 40 μmol/l.

Hepatopathy of the second degree. Clinical symptoms of liver damage are noted: its enlargement, soreness, in some cases hepatic colic, moderate jaundice (total bilirubin up to 80 μmol/l), dysproteinemia, hyperfermentemia with an increase in enzyme activity by 3-5 times.

Stage III hepatopathy (acute hepatic failure). Characterized by CNS damage from encephalopathy to coma, jaundice (bilirubin over 85 μmol/l), more pronounced hyperfermentemia and hemorrhagic syndrome.

Acute nephrohepatopathy in poisoning with nephrotoxic substances is the result of a strictly differentiated effect of a chemical substance on the nephron and hepatocyte. As a result of damage to membranes and intracellular structures in organs, cytolytic processes occur, ending in parenchyma necrosis.

Specific kidney damage with the development of tubular necrosis and intracellular hydropy occurs in cases of poisoning with glycols, heavy metal salts and arsenic. In case of overdose (or increased sensitivity to the drug) of antibiotics, sulfonamides, paracetamol, radiocontrast agents and other drugs, renal dysfunction may occur as interstitial nephritis, tubular or papillary necrosis. Changes in the liver are nonspecific in nature, from cholestatic hepatitis with zones of inflammatory infiltrates in the periportal spaces to widespread centrilobular necrosis.

Chemical substances that have a predominantly hepatotropic effect, with the development of a destructive process in liver cells, include chlorinated hydrocarbons, poisonous mushrooms, a number of medications in case of their overdose - chlorpromazine, halothane, arsenic preparations, etc. Changes in the liver are manifested by fatty degeneration, pigment hepatosis, widespread centrilobular necrosis.

Specific changes in the liver and kidneys also occur in the development of acute hemolysis due to poisoning with organic acids, copper sulfate solution, arsenic hydrogen, and when eating improperly cooked conditionally edible mushrooms - morels and gyromitra. The pathogenesis of this specific nephrohepatopathy (acute hemoglobinuric nephrosis and pigment hepatosis) is not only due to acute hemolysis, but also to a significant extent to the direct toxic effect of the chemical substance (mushroom toxin) on the parenchymatous organs.

Another variant of pathology development in the liver and kidneys, which does not have strictly specific morphological changes in the parenchymatous organs, is non-specific acute nephrohepatopathy. These manifestations are most often a consequence of exotoxic shock, in which impaired blood and lymph circulation, as well as hypoxemia, increase the toxic effect of the chemical substance on the liver and kidneys. Non-specific nephrohepatopathy also occurs in patients with chronic liver and kidney diseases (pyelonephritis, urolithiasis, persistent hepatitis, etc.). In conditions of increased sensitivity to the toxic substance, even a small dose can lead to severe and difficult-to-treat therapy, functional insufficiency of the parenchymatous organs.

A special, specific character of damage to the kidneys and liver is noted in the syndrome of positional compression of soft tissues in the form of myoglobinuric nephrosis and pigment hepatosis. The onset of the syndrome is preceded by poisoning with chemicals (carbon monoxide, car exhaust gases), ethanol and psychopharmacological agents (narcotics, tranquilizers, sleeping pills, etc.) - substances that inhibit the activity of the central nervous system with the development of a comatose state. As a result of compression by the weight of one's own body of atonic striated and smooth muscle vascular muscles in a patient in a forced, motionless position, often with a limb tucked under oneself, damage to soft tissues, and especially striated muscles, occurs. Intracellular myoglobin, creatine, bradykinin, potassium and other biologically active substances enter the general bloodstream in large quantities. The consequence of non-traumatic damage to soft tissues is acute renal and hepatic failure. The damaged limb has a characteristic appearance due to edema: it is compacted and significantly increased in volume. The examination reveals a lack of sensitivity in the distal sections. Active movements are usually impossible, and passive ones are sharply limited.

Treatment of endogenous intoxication syndrome in acute renal and hepatic failure includes two main stages associated with compensatory and adaptive reactions of the body:

• At the compensation stage - the use of methods to enhance natural detoxification and the use of drugs, including antidotes (unithiol), aimed at reducing the formation and activity of endotoxins.
• At the stage of decompensation - the use of complex detoxification that supports the functional activity of the liver and kidneys to remove from the body a wide range of endogenous toxins, the formation of which is associated with PON.

Enhancing natural detoxification includes the following methods:

• forced diuresis according to the generally accepted method is carried out with preserved urinary function of the kidneys in order to remove low-molecular and water-soluble bile pigments, toxic substances of protein origin from the body,
• lactulose solution is prescribed orally at 30-50 ml daily throughout the acute period of the disease to reduce the content of ammonia and other toxic substances of protein origin in the intestine, as well as to enhance intestinal peristalsis and accelerate the removal of toxic substances from the body,
• enterosorbents are used to bind endotoxins in the gastrointestinal tract. They are prescribed orally 3 times a day 1 hour before meals or medications,
• to restore and preserve the structure of hepatocytes, cell membranes, and regulate protein and lipid metabolism, antioxidant and membrane-stabilizing therapy is administered by administering vitamin E, "essential" phospholipids, heptral, glucocorticoids, and vitamins of group B, C, and PP. The drugs actively inhibit free-radical processes in the membranes of hepatocytes and endotheliocytes, normalize transcapillary metabolism and intracellular oxidation-reduction reactions,
• Active artificial detoxification is a combination of dialysis-filtration methods with sorption methods of detoxification, which is indicated for patients with acute renal and hepatic failure, when toxic substances with low-, medium- and large-molecular weight are determined in the body in increased concentrations. In these cases, the patient's blood first enters a column with a sorbent, and then into the dialyzer of the "artificial kidney" device

With the combined use of HDF and hemosorption, treatment is aimed at removing a wide range of toxic metabolites from the body - from 60 to 20,000 daltons. With a combination of the two treatment methods, the clearance of urea is 175-190 ml / min, creatinine - 190-250 ml / min. In severe cases of the disease, treatment is supplemented with plasma sorption. When using two methods, a more pronounced detoxification effect is noted. Thus, with plasma sorption, compared with hemosorption, the elimination of urea, creatinine and total bilirubin is 1.3-1.7 times higher. However, the impossibility of creating a plasma flow of more than 150 ml per minute in the extracorporeal system significantly reduces the overall detoxification effect of the procedures at the body level.

Thus, the treatment of acute renal and hepatic failure in each patient should be strictly individual, the volume and nature of detoxification therapy depends on the general condition of the patient and the data of laboratory and instrumental examination. Complex detoxification of the body requires, in essence, a uniform approach, consisting in a combination of direct detoxification measures with the restoration of disturbed homeostasis parameters. In this case, the choice of detoxification method is determined by its compatibility with the biological environments of the body, as well as the kinetic features of toxic substances associated with their initial level in the blood and the nature of distribution in organs and tissues.

Of decisive importance for the removal of toxic substances from the body is the elimination of the conditions for their entry into the blood (cleansing the gastrointestinal tract, sanitizing septic foci, removing necrotic tissue, restoring liver and kidney function).

It should be noted that achieving a positive effect when using any of the above methods of biological correction is associated with compliance with the specifics of its use (choice of time and dose of exposure, compatibility with other therapeutic measures).

In cases of acute toxicosis, the best results are achieved in cases of early use of artificial detoxification methods, which allows, through the implementation of their preventive capabilities, to prevent complications of the disease.

A differentiated approach to complex detoxification of the body allows us to significantly modify this process, make it more manageable and thereby significantly influence the results of treatment.