Complex detoxification of the body

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

The implementation of a full-fledged detoxification in cases of mild and part of moderate poisoning does not present a difficult problem and is achievable by enhancing the processes of natural detoxification. For the treatment of severe poisoning, it is usually necessary to use methods of artificial detoxification that can purify the blood and other body fluids, regardless of the degree of preservation of the natural detoxification function.

In the toxicogenic stage of poisoning the most successful application of hemosorption. One of the main advantages of hemosorption with the use of nonselective sorbents is its high efficiency with respect to the purification of blood from a wide range of exo-and endogenous toxicants, which, due to their physico-chemical characteristics (formation with protein molecules of large complexes, hydrophobicity) 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 the parameters of homeostasis. This is evidenced by the high clinical efficiency of hemosorption, in spite of the fact that during the operation only 3 to 25% of the total amount of absorbed toxicant is removed from the blood. It was also noted that in cases when there are similar in clearance values, the half-life of toxicants (T1 / 2) during hemosorption is significantly (almost 2 times) shorter than hemodialysis.

In general, as a result of the use of hemosorption, lethality significantly decreases with various types of acute poisoning (by 7-30%).

However, the toxic-kinetic features of various methods of detoxification dictate the need for their combined application with other highly effective detoxification measures.

One of such methods of detoxification is hemodialysis. Low molecular weight toxicants are subjected to the most intensive excretion with this method, therefore DG is widely used in poisoning by them, as well as in ARF, allowing to purify blood from urea, creatinine, to eliminate electrolyte disorders. Due to the insignificant negative effect of HD on hemodynamic indices and blood elements, it can be spent for a long time with perfusion in one session of large volumes of blood, which makes it possible to remove large amounts of toxic metabolites from the body.

In some cases, for example, when poisoning with heavy metal and arsenic compounds, methanol and ethylene glycol, hemodialysis is currently considered to be the most effective method of artificial detoxification of the body. Recently, for more objective determination of indications for the use of hemodialysis or hemosorption, the volume distribution of various toxicants is used, which are published in reference books. For example, if the volume of distribution is less than 1.0 l / kg, the toxicant is distributed mainly by the vascular volume of the body's bio-environment, then hemosorption is recommended, and if more than 1.0 l / kg, it is better to use hemodialysis, volume of bio-media containing exogenous or endogenous toxicants.

Widespread introduction of such modifications as isolated UV blood, GF and GDF, allow more efficiently to purify the blood from medium molecular toxicants and to carry out a rapid correction of the water-electrolyte and acid-base balance. In the latter case, these advantages of filtration methods make it possible to refer them to the number of resuscitation measures. One of the simple and popular methods of artificial detoxification is peritoneal dialysis. Using the peritoneum as a dialysing membrane with a large surface makes it possible to excrete larger molecules in the PD process, which considerably expands the range of toxic substances removed from the body.

Along with the problem of detoxification of blood, it is extremely important to remove toxicants from the intestine in order to prevent their absorption into the blood and maintain its toxic concentrations in it. To eliminate the created depot, intestinal lavage is used, which allows to significantly shorten 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 hemodynamic disorders.

The combination of methods for enhancing natural detoxification and sorption therapy with methods of enhancing biotransformation leads to an acceleration of the excretion of toxicants from the body by a factor of 1.5-3. For example, the rate of excretion of toxicants of psychotropic action increases significantly when combined with HCN. In this process, the process of cleansing the body is accelerated due to the fact that the toxicant is intensely oxidized with the help of HCN, the infusion of which is carried out during hemosorption.

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

[1], [2], [3], [4]

Complex detoxification of the organism in the somatogenic stage of poisoning

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

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

At the same time, exposure to the toxic concentration of "biogenic" toxicants is no less dangerous than the previous influence of xenobiotics. The outcome of endogenous intoxication - gross violations of microcirculation, 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 aggravation of hemodynamic disorders, worsening of treatment outcomes in general.

The most pronounced endogenous intoxication most often develops in acute poisoning with hepato- and nephrotoxic substances due to a violation of the specific function of the liver and kidneys - the organs responsible for inactivation and removal of toxic substances from the body. The accumulation of pathological metabolism products, active enzymes of intracellular organelles and tissue hormones in the body leads to the activation of LPO, kallikrein-kinin system and intracellular hypoxia. In conditions of increased vascular permeability and disturbed homeostasis, cytolysis develops, vital organs lose their specific function. Under the influence of endotoxins, the hormonal background changes, the immune system is depressed, 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 1st degree is manifested by insignificant 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 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 2nd degree is manifested by oliguria, moderate azotemia, expressed and prolonged morphological changes in the composition of urine (up to 2-3 weeks). At the same time, significant proteinuria, macrohematuria, cylindruria are noted, the presence of renal epithelial cells in the urine sediment of CF is reduced 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 a picture of acute nephrosis of pigmentary, hemoglobinuric, myoglobinuric or hydropic.

Nephropathy of the third degree (OPN) is characterized by oppression of all renal functions by oligoanuria or anuria, high azotemia, a sharp decrease or absence of CF, suppression or cessation of water reabsorption in tubules. These changes are accompanied by a severe clinical picture due to impaired function of other organs and systems in the form of multi-organ pathology.

Hepatopathy I degree. On examination, there are no clinical signs of liver damage. Dysfunctions of the liver are characterized by a moderate increase (by 1.5-2 times) of the activity of cytoplasmic enzymes with their normalization by the 7th-10th day, slightly expressed by hyperbilirubinemia - no more than 40 micromol / l.

Hepatopathy of the second degree. There are clinical symptoms of liver damage, its increase, soreness, in some cases hepatic colic, mild jaundice (bilirubin total to 80 μmol / l), dysproteinemia, hyperfermentemia with an increase in the activity of enzymes 3-5 times.

Hepatopathy of the third degree (acute PN). It is characterized by CNS damage from encephalopathy to coma, jaundice (bilirubin over 85 μmol / l), more pronounced hyperfermentemia and hemorrhagic syndrome.

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

Specific damage of the kidneys with the development of tubular necrosis and intracellular hydropypeia occurs when poisoning with glycols, salts of heavy metals and arsenic. In case of an overdose (or hypersensitivity to the drug) of antibiotics, sulfonamides, paracetamol, radiocontrast agents and other drugs, renal dysfunction may be classified as interstitial nephritis, tubular or papillary necrosis. Changes in the liver are nonspecific in nature from cholestatic hepatitis with zones of inflammatory infiltrates in periportal spaces to widespread centrolobular necrosis.

To chemical substances possessing predominantly hepatotropic action, chlorinated hydrocarbons, poisonous fungi, a number of drugs with their overdose - chlorpromazine, halothane, arsenic preparations, etc., are involved in the development of the destructive process in liver cells. Changes in the liver are manifested by fatty dystrophy, pigmentary hepatosis, widespread centrolobular necrosis.

The specific nature of changes in the liver and kidneys is also in the development of acute hemolysis due to poisoning with organic acids, a solution of copper sulfate, arsenic hydrogen, when eating improperly cooked conditionally edible fungi - morels and stitches. In the pathogenesis of this specific nephrogepatopathy (acute hemoglobinuria nephrosis and pigmentary hepatosis) lies not only acute hemolysis, but also to a large extent the direct toxic effect of the chemical substance (fungal toxin) on the parenchymal organs.

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

A special, specific character of kidney and liver damage is noted in the syndrome of positional compression of soft tissues in the form of myoglobinuric nephrosis and pigmentary hepatosis. The appearance of the syndrome is preceded by poisoning with chemicals (carbon monoxide, vehicle exhaust gases), ethanol and psychopharmacological agents (drugs, tranquilizers, hypnotics, etc.) - substances that depress the activity of the central nervous system with the development of a coma. As a result of compression of the weight of his own body with an atonic transverse striated and smooth muscle vascular musculature in a patient who is in a forced, immobile position, often with a limb tucked under himself, soft tissues, and especially the striated muscle, are damaged. In large quantities, intracellularly contained myoglobin, creatine, bradykinin, potassium and other biologically active substances enter the total bloodstream. The consequence of non-traumatic damage of soft tissues is acute renal-hepatic insufficiency. The damaged limb has a characteristic appearance due to the edema, it is compacted and significantly enlarged in volume. The study notes a lack of sensitivity in the distal areas. Active movements, as a rule, are impossible, and passive ones are sharply limited.

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

• At the compensation stage, the use of methods for enhancing natural detoxification and the use of medications, including antidotes (unitiol), aimed at reducing the formation and activity of endotoxins.
• At the stage of decompensation, the use of a complex detoxification supporting 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 the PON.

Enhancement of natural detoxification includes the following methods:

• forced diuresis according to the conventional method is performed with preserved urinary function of the kidneys in order to remove from the body low-molecular and water-soluble bile pigments, toxic substances of protein origin,
• a solution of lactulose is prescribed internally for 30-50 ml daily for the entire acute period of the disease to reduce the intestinal ammonia and other toxic substances of protein origin, as well as to enhance intestinal motility and accelerated elimination of toxic substances,
• Enterosorbents are used to bind endotoxins in the gastrointestinal tract. They are prescribed orally 3 times a day for 1 hour before a meal or medication,
• antioxidant and membrane-stabilizing therapy with the introduction of vitamin E, "essential" phospholipids, heptral, glucocorticoids, vitamins of group B, C, PP are used to restore and preserve the structure of hepatocytes, cell membranes, regulation of protein and lipid metabolism. Preparations actively inhibit free radical processes in membranes of hepatocytes and endotheliocytes, normalize transcapillary exchange and intracellular redox reactions,
• active artificial detoxification is a combination of dialysis-filtration methods with sorption methods of detoxification, which is shown to patients with acute renal-hepatic insufficiency, when toxic substances with a low, medium and large-molecular weight are detected in the body in an increased concentration. In these cases, the blood from the patient first goes to the column with the sorbent, and then to the dialyzer of the "artificial kidney"

With the combined use of GDF and hemosorption, the treatment is aimed at removing from the body a wide range of toxic metabolites - from 60 to 20 000 daltons. When combined, the two methods of treatment urea clearance is 175-190 ml / min, creatinine - 190-250 ml / min. In severe disease, treatment is supplemented by plasma sorption. When carrying out the two methods, a more pronounced detoxification effect is noted. Thus, for plasmosorption in comparison with hemosorption, the elimination of urea, creatinine and total bilirubin is 1.3-1.7 times higher. However, the inability to create in the extracorporal system a plasma flow of more than 150 ml per minute significantly reduces the overall detoxification effect of procedures at the organism level.

Thus, the treatment of acute renal-hepatic insufficiency in each patient must be strictly individual, the volume and nature of detoxification therapy depends on the general condition of the patient and the data of the laboratory-instrumental examination. Complex detoxification of the body requires, in fact, the same type of approach, consisting in combining directly detoxification measures with the restoration of disturbed parameters of homeostasis. At the same time, the choice of the method of detoxification is determined by its compatibility with the biological media of the organism, as well as by the peculiarities of the kinetics of toxic substances associated with their baseline blood level and the distribution pattern in organs and tissues.

The decisive importance for the removal of toxic substances from the body is the elimination of the conditions for their entry into the blood (purification of the gastrointestinal tract, sanitation of septic foci, removal of necrotic tissues, restoration of liver and kidney function).

It should be noted that the achievement of a positive effect when applying any of the above methods of biological correction is due to the observance of the peculiarities of its use (the choice of the moment and dose of exposure, compatibility with other therapeutic measures).

In acute toxicoses, the best results are achieved in cases of early application of artificial detoxification methods, which, through the realization of their preventive capabilities, prevents complications of the disease.

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