SEPSIS. ENDOTOXICOSIS IN SURGERY. DETOXIFICATION OF ORGANISM

SEPSIS

Sepsis — general nonspecific infection of an organism, caused by different agents and occurring against a background of a changed organism’s reacttivity irrespective of the agent, is characterized by the same clinical picture similar to endotoxicosis phenomena and poly-organ disorders.

Sepsis should be examined as the gradual development of local suppurative focus, when generalization of the infection takes place in the hematogenous and lymphogenous ways. The lethality with sepsis is high and according to different authors ranges from 40 to 60%, and in the case of septic shock it reaches 85%.

Pathogenesis of sepsis is considered by the interaction of three factors:

The causative agent.

Primary focus.

Organism reactivity.

Causative agents of sepsis can be almost all the pathogenic and conditional-pathogenic microorganisms. Frequently, they are staphylococci, streptococci, Pseudomonas aeruginosa, Proteus bacteria, anaerobic flora, bacteroids.

Generally the basic agent of sepsis is staphylococcus, the second one is E.coli, especially in the case of peritoneal and gynaecologic sepsis. The kind of agent, its biological properties (production of exo- and endotoxins), virulence, sensitivity to antibiotics, antiseptics determine the features of the clinical picture of sepsis. For example, staphylococcal, bacteroidal (anaerobic) sepsis, as a rule (95% of the cases), is accompanied by the development of secondary metastatic abscesses. Streptococcal, Pseudomonas aeruginosa sepsis has the course similar to hematosepsis with pronounced endotoxicosis without the formation of secondary metastatic abscesses.

With sepsis, there is always an entrance gate and a primary focus of infection. The entry of infection, or place where the infection occurs, is damaged tissue. The primary focus is considered the site of inflammation, occurring at the site where the infection appeared and is the source of its generalization. The primary focus, as a rule, coincides with the entry of infection. Very seldom it arises at some distance from the place of infection penetration, for example, suppurative lymphadenitis and phlegmon, as the result of attrition of the foot skin. The primary foci during sepsis can be different wounds, local suppurative processes (furuncule, anthrax, phlegmon, mastitis, osteomyelitis), destructive diseases of the internal organs with the development of empyema of the pleura, peritonitis.

In the primary focus that contains plenty of dead tissue, blood clots, bacteria divide rapidely. The microbe’s exo- and endotoxins damage the walls of the wound, new vessels, resulting in thromboses, increase in the vascular wall permeability, increase in necrosis processes. All this causes infringement or full destruction of the granulation shaft of the inflammatory focus, increase in the permeability of toxins and microbes into the general blood flow (bacteriemia).

The infection spreads from the center of damage hematogenously or lymphogenously or simultaneously. The hematogenous way is characterized by the development of thrombophlebitis, periphlebitis, thrombembolism and frequently the formation of secondary suppurative metastatic foci. The lymphogenous way of spreading is observed less often because the lymph nodes are a filtering barrier for the infection. The primary focus during sepsis is not only a reservoir of the infection but renders the sensitizing action on the patient’s organism.

A patient’s organism reactivity has crucial importance in the development of sepsis. Sepsis develops as the result of exhaustion of the antiinfectious immunity under the influence of the primary focus. As a result of the action of a significant amount of agents and their toxins, destruction of tissue, infringement of regional blood circulation in the primary focus, there is a temporary relative deficiency of protection factors (opsonin, phagocytes). It results in uncontrolled increase in microbes in the penetration areas (infection entry) and the development of the suppurative process. With insufficient mobilization of immune protection factors in the primary focus there is an exceeding in the allowable ratio of microbe-phagocytes, causing destruction of the phagocytes and the beginning of the secondary immunodeficiency development. With an increase in the duration of this process, the superfluous amount of antigenes and microbic toxins leave the borders of the primary focus. Thus, factors of natural resistency and specific immune response are oppressed. Thus, with sepsis there is a deficiency of factors of immune protection, which now are not capable of restricting the damaging action of microbes and toxins on the basic physiologic systems of an organism.

The reaction of a person’s organism to the sensitization of microbic antigene during sepsis can be different:

Normergic with the prevalence of the inflammation phenomena, the clinical picture is characterized by the presence of secondary metastatic abscesses.

Hyperergic with the prevalence of destructive-degenerativechanges in the tissue, rapid course with the endotoxicosis phenomena, allergy and toxic shock.

Anergic (hypergic) is characterized by languid inflammatoryreaction with a decline in the reactive forces of an organism.

One of the leading factors, which determines the course of sepsis, is toxinemia (microbic toxins, products of tissue disintegration) which results in the development of the intoxication syndrome (endotoxicosis) with severe infringements of the function and morphology of vital organs and systems (cardiovascular and respiratory systems, liver, kidneys, haemopoietic organs, etc.).

Classification. Many classifications of sepsis are suggested. The basic ones are as follows:

І. According to the type of the causative agent: staphylococcal, streptococcal, colibacillar, anaerobic, bacteroidic, mixed, etc.

According to the source: wound, postoperative, therapeutic, cryptogenic.

According to the localization of the primary cell: gynaecologic, otogenous, dontogenous, urological, umbilical and so forth.

According to the acuteness of the clinical picture: lightning,acute, subacute, relapsing, chronic.

According to the time of development: early (till the 14th dayfrom the moment of damage) and late (after the 2 week from the moment of damage).

According to the character of reaction of an organism to thebacterial antigene: hyperergic, normergic, allergic (hypergic).

According to the clinical-morphological attributes: hematosepsis(without metastasises), septicopyemia (sepsis with purulent metastasises).

Clinical picture. The clinical picture of sepsis is very diverse and depends upon many conditions: etiological moments, type of agent, organism’s reaction. In some cases, it is very difficult to determine the diagnosis of sepsis. The diagnosis of sepsis should be based upon the following parts: revealing the primary focus, set of typical clinical features, data from blood inoculation (haemoculture).

First of all, sepsis should be distinguished from pyo-resorptive fever. Pyo-resorptive fever is a transitive phase from local suppurative process to sepsis, observed at any localization of suppurative foci and characterized by the general reactions of an organism (fever, chills, intoxication), occurring against a background of absorption of tissue disintegration products from the purulent cell.

Unlike to sepsis, with pyo-resorptive fever after radical therapy of the suppurative focus (incision, drainage, removing the source of infection) the general phenomena start to disappear, remaining for 7 days. During the blood exam, as a rule, bacteriemia is absent.

Pyo-resorptive fever by extent of general phenomena always corresponds to the severity of damage in the local focus. At last, recently in clinic, the test for determining the bacterial level by 1 g of tissue was successfully applied. With pyo-resorptive fever, the bacterial level, as a rule, is lower than 105 microbes/1 g of tissue.

When determining the diagnosis of sepsis, a set of most often signs are used. The character and frequency of clinical semiology are resulted in the table.

The primary focus is one of the basic symptoms of sepsis. With its development, in the primary focus, alternative processes prevail (anemic wound, secretion is insignificant, purulent, frequently ichorous, almost undeveloped granulation tissue).

The majority of surgeons believe that there is sepsis in surgery without the infection entry and practically always is secondary, i.e. develops with the presence of a primary focus of infection (wound, purulent local process, operative intervention, etc.). The exam of the bacterial level by 1 g of tissue taken by the way of biopsy of the primary or metastatic focus helps in the diagnosis of sepsis. A number of researchers (M. I. Kuzin, V. M. Kostyuchenok, V. M. Buyanov) proved, that the seeding of 105 of cells and more by 1 g of tissue is critical and is evidence of the rapid development of infection in the wound and possible generalization. For patients with acute sepsis (75% of the cases) the critical level (105 cells by 1 g of tissue) of primary and metastatic foci appeared to be increased (V. M. Kostyuchenok, A. M. Svetukhin).

Table Clinical symptomatology of sepsis (according to B. I. Dmytriyev, 1999)

Fever is one of the most significant attributes of the infection generalization. Rhythmic type of fever is mostly observed in patients with septicopyemia phenomena. Hectic fever with a constant rise in temperature up to 38.5–39°C  testifies to unfavourable progressing of the process, observed in patients with septic shock, frequently with a lethal outcome. Wavy fever with a low level of increased temperature is observed in the subacute course of sepsis, characteristic for therapeutic sepsis and certain patients with gynaecologic sepsis. The temperature reaction is absent in patients with hyporeactive course of sepsis.

Hemodynamic infringements are closely connected to the depth of metabolic disorders, severity of endotoxicosis, extent of hypovolemia. Haemodynamic infringements with the generalization of infection are pronounced by a decrease in ABP, color index, tachycardia, reduction of blood volume, infringement of the contracting function of the myocardium.

One of the most characteristic and constant attributes of toxic injury of the myocardium during sepsis is tachycardia, which increases with the growth in endotoxicosis, frequently kept even with the normalization of temperature. Sometimes, infringements of blood circulation during sepsis can have a rapid course with the development of the clinical picture of septic shock. Thus, acute arterial hypotension is observed, tachycardia changes to bradycardia with arrhythmia, impairment of consciousness (coma), severe respiratory insufficiency, such as respiratory distress-syndrome, functional infringements of the liver and kidneys (oliguria, anuria) develop.

Infringements of the renal function, such as toxic nephritis, frequently worsen the clinical course of sepsis, causing oliguria with azotemia phenomena, change in urine (proteinuria, leukocyturia, erythrocyturia, cylindruria), development of peripheral hypostases. The subsequent progressing of the process with transition into anuria and the development of acute renal insufficiency have a decisive influence on the prognosis and lethality for this group of patients. Infringements of the electrolytic balance and acid-base structure of the blood, which cause hyperkalemia, hyponatremia, the occurrence of metabolic acidosis or alkalosis, are closely connected to toxic nephritis phenomena.

Toxic hepatitis — one of the characteristic symptom-complex. It causes both the liver enlargement and its dysfunction: jaundice, hyperfermentemia transaminases, alkaline phosphatase, lactate dehydrogenase, infringement of the protein-synthetic function (hypoproteinemia, disproteinemia). Acute hepatic insufficiency can develop sometimes.

Infringements of the blood coagulating system during sepsis manifest itself very brightly in the disseminated intravascular coagulation syndrome (DIC). In development of DIC-syndrome during sepsis, two phases are found:

Hypercoagulation with the activation of plasma fermental systems. It causes thrombophlebitises, spontaneous migrating thromboses.

Hypocoagulation with the exhaustion of coagulation mechanisms. It causes emigration or profuse bleedings, microcirculation blockade in organs (“shock lung”, acute renal and hepatic insufficiency, infringement of brain circulation).

Respiratory insufficiency during sepsis is the result of intoxication and direct action of microflora on the lung parenchyma (septic pneumonia, abscesses). Toxic damage of the pulmonary tissue causes dyspnea, phenomena of hyperhydration of the lungs, occurrence of septic pneumonias, development of respiratory distress-syndrome.

Toxic damage of the CNS appear the first days after generalization of the process, such as encephalopathy (headache, annoyance, depression, apathy, sleep disorders). Progressing endotoxicosis and accompanying toxic damages of the liver and kidneys can result in the development of deep mental infringements (coma, intoxication delirium).

Changes in the peripheral blood is an important diagnostic and prognostic criterion of sepsis. Changes in the red blood appear as hypochromic anemia, anisocytosis, poikilocytosis, decrease in the color index, increase in ESR.

Characteristic changes in the white blood: increased leukocytosis, toxic granularity of leukocytes, left shift of neutrophilic formula (occurrence of young, immature forms of leukocytic forms in the peripheral blood). Expressiveness of leukocytosis depends upon the character of the organism’s reactivity, kind of a pathogenic organism. Especially high leukocytosis is observed with staphylococcal sepsis, less pronounced — with gram-negative sepsis. Pseudomonas sepsis is characterized by leukopenia more often, especially with progress of the process. Leukopenia is frequently observed in the terminal stage of endotoxicosis, during septic shock. Normalization of the amount of leukocytes with the decrease in endotoxicosis is a favorable attribute, which testifies to efficient therapy. Enlargement of the spleen is a frequent symptom of sepsis, which reflects a toxic action of microflora and the development of degenerative changes in the organ, that is evidence of a decrease in the detoxification functions.

Bacteriemia — one of the basic symptoms which confirm the diagnosis of sepsis. Blood inoculation during sepsis do not always reveal bacteriemia. According to different authors (V. Ya. Shlapobersky, I. G. Rufanov, M. I. Kuzin, Yu. Ya. Belokurov, A. M. Torbinsky) the per cent of revealed bacteria ranges from 22 up to 87. In order to improve the results of haemoculture many factors are important: choice of optimum nutrient mediums, carefulness of technique performance, numerous inoculations, whenever possible at the height of fever attack. With a negative blood inoculation with nonclaustrid forms of anaerobes are not identified as a rule. It requires special conditions of identification, expensive equipment, which is still inaccessible for practical public health service (A. P. Kolyesov, M. I. Kuzin, P. M. Tchuyev) are not identified.

Sepsis is accompanied by pronounced endotoxicosis, the level of which is estimated by general-toxic tests: toxic metabolites of the blood (kreatinine, urea, residual nitrogen, etc.), medium-molecular oligopeptides, paramecin test, leukocytic index of intoxication, hematological index of intoxication, etc.

After the depth of infringements and the level of possible compensatory reactions, the condition of the detoxification organs (liver, kidneys) endotoxicosis during sepsis can be divided into three degrees of severity (A. M. Torbinsky):

I degree — compensation;

ІІ degree — subcompensation;

ІІІ degree — decompensation.

The estimation of the severity of endotoxicosis has important practical value, because it allows the application of optimum methods of detoxification. The development of sepsis and the progress of endotoxicosis results in radical infringements of the cellular and humoral parts of the immune system, causing the occurrence of secondary Т-immunodeficiency, decrease in phagocytosis (decrease in the phagocytal activity of leukocytes, decrease in the level of complement, accumulation of circulating immune complexes).

Treatment of sepsis should consist of the following major factors:

action on the primary cell;

correction of homeostasis infringements;

complex detoxification therapy.

Action on the primary and metastatic foci provides active surgical policy: wide incision, necretomy, flowing washing with active aspiration of the secretion (vacuum-devices), application of ultra-violet and laser action, treatment under abacterial conditions (abacterial therapeutic device-3 (ATD-3), АТD-5, etc.); application of hyperbaric oxygenation (different types of pressure wards).

Action on agents organisms is done with rational antibiotic and antiseptic therapy. Antibiotic therapy is conducted under the obligatory control of an antibioticogram and blood inoculation (every 4– 5 days). Antibiotics are applied in maximal dozes, entered intravenously, intraarterially, endolymphatically. More often semisynthetic penicillin (Ampicillin, Carbenicillin), aminoglycosides (kanamycin, gentamycin, sisomicin, amikocin), cephalosporins (cefamezin, kefzol, claphoran), imipenem (thienam) are applied. Combine antibiotics with antiseptics (dioxydin, furagin, flagylum, metranidasole), sulfanilamide (etazole, sulfalen, biseptol). Thienam is the mostly effective.

Correction of homeostasis infringements includes actions directed upon the normalization of parameters of constancy for the organism’s internal environment: haemodynamics, protein, water-electrolyte, acid-base balances, coagulation system, immune status, improving the detoxification functions of systems and allocation of toxins (liver, kidneys, lungs, intestines).

Correction of haemodynamics is carried out under controlled haemodilution with the application of blood substitutes, colloidal and crystalloid solutions (olyglucin, rheopolyglucin, lactosil, trisil, acesil, Ringer—Lock’s solution, Darrow’s solution), disaggregants (trental, complamin, bensohexon, rheopolyglucin). In order to improve rheology of the blood and correction of the DIC-syndrome along with disaggregants they apply heparin, inhibitors of proteolytic enzymes (contrical, gordox), chilled plasma, fibrinolytic active plasma (FAP).

In order to correct hypoproteinemia and disproteinemia they apply dry native, chilled plasma, albumine, protein, albuminous hydrolysate, amino acid solutions.

In order to correct the water-electrolyte and acid-base balance infringements they apply electrolytic solutions (N1 and N2), Darrow’s solutions, panangin, calcium gluconate, sodium bicarbonate, as well as inhibitors of proteolysis and anabolic hormones (nerobol, retabolil).

Correction of the immune status during sepsis is conducted by passive immune therapy and active immune correction. Passive (replaceable) immune therapy is carried out by repeated transfusions of fresh-stabilized blood (fresh-citrate, heparinized), the application of hyperimmune (antistaphylococcal, antipseudomanal) plasma or gamma globulin, interferon, bacteriophage. Active immune correction is carried out with preparations of the thymus (thactivin, timosin, thymalin, thymogen), bone marrow (mielopeptide, β-activin), synthetic immune correctors (decaris, dauciphon) taking into account the degree of developing secondary immunodeficiency.

The therapy directed on improving the function of the detoxification systems is conducted: the liver (vitamins of group B, C, methionine, legalon, aecenciale), the kidneys (forced diuresis), the lungs (oxygen tent, pressure ward, artificial ventilation lung (AVL) during septic shock), intestines (intubation, electrostimulation, enterosorption).

Correction of endotoxicosis during sepsis should be conducted concerning the basic liquid mediums of an organism (blood, lymph) at the same time, taking into account the extent of endotoxicosis. Detoxification therapy should be directed upon strengthening the function of the basic detoxification organs (the liver, the kidneys, the lungs, the intestines) with compensated infringements of their function, in case of subcompensation or decompensation — partial or full replacement of their functions.

During compensated infringements, the application of intracorporal methods of detoxification, haemoinfusion, endolymphatic detoxification (haemodesum, neoheamodesum, albumine against a background of forced diuresis), enterosorption (carbovit, enterosorf), application sorption (activated carbon fibrous materials), intravascular laser irradiation of the blood (ILIB), ultra-violet irradiation of the blood will be effective.

With deep forms of endotoxicosis (II–III stage) intracorporal methods of detoxification are ineffective. They should be supplemented by extracorporal detoxification taking into account the mechanism of action and most pronounced detoxification effect. With acute hepatic insufficiency, haemosorption, lymphosorption, plasmosorption, plasmapheresis are applied, which models to a ceratin extent the detoxification function of the liver. Haemodialysis, haemofiltration, and haemodiafiltration (application of “artificial kidney” devices in different operating modes) are especially indicated with acute renal insufficiency. Realization of complex detoxification gives an opportunity to considerably improve the results of treatment and reduce lethality rate, especially with deep forms of endotoxicosis (from 65–80% up to 35%).

Treatment of patients suffering from sepsis should be carried out in departments of intensive therapy and resuscition, equipped with modern diagnostic and medical equipment for extracorporal detoxification.

ENDOTOXICOSIS DURING PURULENT SURGICAL PATHOLOGY

Principles and Methods of Correcting Endotoxicosis

Endogenous intoxication syndrome is the principal cause of death in patients suffering from purulent infection. Endotoxicosis during a purulent surgical pathology has a complex aetio-pathogenesis, which includes impairment of the majority of organs and systems of an organism. Displays of endotoxicosis during purulent infection can arise against a background of significant damages of tissue (burns, frost bite, syndrome of long compression, extensive traumas with necrosis of the soft tissue), destructive purulent diseases of the internal organs (pancreatitis, cholecystitis, appendicitis, etc.), as well as against a background of infringement of the natural detoxification systems (renal, hepatic insufficiency).

According to modern views, aetio-pathogenesis of the intoxication syndrome during purulent infection consists of the following basic central factors:

Metabolic infringements in the primary focus of infection under the action of microbic toxins and enzymes.

Infringements to the barrier functions of tissues and organs asa result of basic changes in haemodynamics and microcirculation, resulting in toxemia.

Infringement of the system of binding and transporting toxicsubstances from tissue to the excretory organs.

Infringement to the detoxification systems of an organism.

Infringement to the system of toxins allocation from an organism.

The factor of the primary focus is determined by the action of microflora as a result of the tissue hypoxia development with infringement to metabolism against a background of traumatic or inflammatory destruction of tissue. Pathogenic properties of the agents of purulent infection are predetermined by proteolytic, necrotic, plasmocoagulation action of bacterial exo- and endotoxins, bacterial enzymes. It results in infringement of endocellular homeostasis, development of infringements of cellular metabolism, change in the permeability of cellular membranes and, consequently, allocation of toxic products into the interstitial space and liquid mediums (blood, lymph).

In the primary focus of infection, pronounced infringements of metabolism processes are marked. As a result of the infringement of digestion of fats and carbohydrates, protein-dependant energetic exchange arises when the basic energy source for cells are amino acids. It results in sharp activation of proteolysis in tissue and blood, disintegration of protein structures of the vital organs. Hypoproteinemia develops, which leads to disorders of synthesis of proteins necessary for regeneration, haemostasis, and immune protection.

In blood and tissues, medium molecular oligopeptides, so-called meddle-size molecules (MSM), which are the intermediate products of proteolysis, accumulate. The structure of substances which enter the pool of MSM is very diverse: glycopeptides, nucleopeptides, oligocarbohydrats, etc. Medium -size molecules have a whole spectrum of negative action on an organism: oppression of erythrogenesis with the occurrence of anemia, oppression of  gluconeogenesis and DNA synthesis, infringement of processes of tissue respiration with suppression of mitochondria functions. The MM has cytotoxic and immunodepressive action (oppression of phagocytar activity of leukocytes, delay in formation precipitate of lymphocytes).

The definition of MSM is an extremely informative test of endotoxicosis during different diseases, which are accompanied by increased proteolysis against a background of generalization of infection (peritonitis, pancreatitis, sepsis, extensive traumas, burns). It gives an opportunity to authentically determine the depth of endotoxicosis, estimate the prognosis and efficiency of the applied therapy. An essential role in the pathogenesis of endotoxicosis is infringements of the lipid metabolism, in particular peroxide oxidation of lipids (POL). During pathology, the antioxidant system frequently suffers, resulting in the accumulation in the organism of highly toxic products of POL (aldehydes, ketone, fatty acids, oxidations), i.e. lipid peroxidation syndrome develops. Damage to the membrane lipids, lipoprotein, swelling and destruction of mitochondria and lysosomes, inactivation of enzymes, infringement of cellular division and phagocytosis are observed. The marked metabolic infringements (proteolysis, peroxidation of lipids) promote the entering of a significant amount of vasoactive substances (catecholamin, kinin, histamine, serotonin, etc.) into the circulating blood, resulting in significant changes in the blood circulation, microcirculation. Vasoactive substances promote dilatation of the peripheral vessels, increase in permeability of the vascular wall, suppress tissue respiration and oxidizing phosphorylation. It worsens endotoxicosis. Infringements of tissue microcirculation amplify as a result of aggregation of erythrocytes, increase in blood viscosity, delay of blood circulation and deposition of blood in tissues. These infringements can lead to the development of disseminated intravascular coagulation syndrome (DIC-syndrome). The DIC-syndrome causes acute functional insufficiency of vital organs (lungs, kidneys, liver, brain), which can cause lethal consequences.

Infringements of the system of bending and transport of toxins to sites of allocation from the organism (the kidneys, the gasterointestinal tract (GIT), the lungs, the skin) have great value in the development of endotoxicosis. This system consists of transport (gastrointestinal tract) and the binding function of erythrocytes, protein, plasma (albumen, antibodies), buffer blood systems. Erythrocytes are capable of adsorbing endotoxins, biological amines, medium molecules on the surface. Oppression of erythrogenesis and destruction of erythrocytes under the action of bacterial toxins, occurrence of anemia considerably reduce the erythrocytes’ transport function of toxins.

The detoxification effect of albumin is predetermined by the formation of easily dissociated bonds with molecules of many organic and inorganic compounds, thus, the toxic properties of the transported toxins decrease. Besides, albumin causes natural haemodilution and improves tissue microcirculation. Infringements of albuminous exchange during purulent infection (hypoproteinemia, hypoalbuminemia) considerably reduce the transport and detoxification function of plasma, promote the increase of endotoxicosis. A significant role in detoxification is played by the buffer blood system intended for the preservation of acid-base balance between the blood and interstitial liquid. The accumulation of significant amounts of un-oxidized products of metabolism in the blood and tissue during the generalization of infection promotes the occurrence of infringements of buffer systems (metabolic acidosis, alkalosis).

The central organ of detoxification is the liver, which carries out the transformation of toxic substances into nontoxical metabolites due to processes of oxidation, hydrolysis, renewal, conjugation which occur in hepatocytes. Kupffer’s cells provide clearing of the blood from bacteria, toxins, immune complexes, products of disintegration. During the generalization of infections under the action of microflora, toxic and destructive damages of the hepatic parenchima, which causes hepatic insufficiency and a decrease in the detoxification functions, are observed. It has crucial importance for the liquidation of endotoxicosis and the prognosis of the disease.

Functional hepatic insufficiency such as toxic hepatopathy is observed approximately in 80% of the patients with sepsis. It appears as intrahepatic cholestasia with jaundice phenomena, infringements of hydrocarbonic exchange and fermental function (hyperglycemia, hyperfermentemia transaminase, lactadehydrogenase, alkaline phosphatase), infringements of protein-synthetic function of the liver (hypoproteinemia, hypoalbuminemia, prothrombinopenia). Infringements of the coagulation system and the development of the DICsyndrome are closely connected with damage to the liver.

For the correction of endotoxicosis, normal functioning of the systems removing the toxins from the organism (kidneys, lungs, GIT) has great value. The kidneys take the central place in the system removing toxins from the organism. Infringements of renal function sharply worsen endotoxicosis during the generalization of infection not only as a result of the accumulation of toxic products, but also through the disorders of homeostasis regulation (ionic blood structure, acid-base balance). With sepsis, two kinds of acute renal insufficiency (ARI) can develop: prerenal and renal. Prerenal ARI is predetermined by infringements of haemodynamics (vasodilation, reduction of filtration efficiency as a result of renal ischemia), it has a reverse nature and renews with the normalization of haemodynamics. Renal ARI develops on the basis of toxic damage or direct microbic action on the renal parenchyma (glomerulonephritis, pyelonephritis) with the development of nephropathy. Clinically it appears as infringement of diuresis (oliguria with conversion into anuria), change of urine structure (proteinuria, cylindruria, bacteriuria). Decrease in osmotic clearance, clearance of free water and sodium are observed on this background (azotemia, hypercreatinemia, increase in the contents of medium molecules in the blood and urine).

Progressing oliguria, development of anuria result in the occurrence of respiratory distress-syndrome (RDS), or “shock lungs”, characterized by hyperhydration of pulmonary tissue (hypostasis lung), acute respiratory insufficiency and hypercapnia. Thus, arterial anoxemia and general anoxemia of organs and tissues grow.

During sepsis, there can be toxic damage to the GIT (stress ulcers of the stomach and intestines, intestinal bleeding, paralytic impassability), resulting in a decrease in the allocation of toxins through the intestines, and endotoxicosis can worsen.

The marked infringements of the detoxification systems and systems removing toxins during the generalization of infection frequently incorporate with each other, i. e. polyorgan insufficiency syndrome (POIS) occurs, giving high lethality rate. It is quite obvious that treatment of endotoxicosis with purulent infection should be carried out in a complex taking into account the difficult aetio-pathogenesis with simultaneous action on the basic parts of this process. Only complex detoxification with correction of homeostasis can change the vicious circle of endotoxicosis formation and reduce lethality rate. For successful correction of endotoxicosis with purulent infection it is necessary to follow the main principles:

Detoxification should be carried out concerning the basic mediums of an organism (blood, lymph).

Detoxification therapy should be the directed upon strengthening the function of basic organs of detoxification and excretion (the liver, the kidneys, the intestines, the skin) with compensated infringements of function, partial or full replacement of their functions in case of subcompensated and decompensated infringements. With compensated infringements, the application of intracorporal methods of detoxification (hemoinfusion detoxification, endolymphatic therapy, enterosorption, application sorption, laser therapy) is effective enough. Detoxification of the blood and lymph during the light degree of endotoxicosis is conducted effectively by the introduction of detoxification substances into the blood or lymphatic system (haemodesum, neohaemodesum, albuminum, polydesum). Detoxification is possible to carry out against a background of controlled haemodilution — forced diuresis with the application of saluretics and osmodiuretics — lasixum, manitol). Application of enterosorption gives an opportunity to strengthen the detoxification effect by the sorption of toxins which excrete through the intestinal tract. For enterosorption activated coal (granulated sorbents, such as carbovitum, etc.), preparations of polyvinylpyrolidone (enterodesum, enterosorpt) are used.

Application sorption is mainly applied with the presence of volumetric wounds, burns (coal sorbents such as carbovitum or carbon fibrous materials). It promotes the sorption of toxins and microorganisms on the wound surface, reduces the degree of bacteria in the wounds, promotes its fast clearing from necrotic mass and development of granulations. At the same time last years laser therapy (intravascular laser blood irradiation, irradiation of wounds with unfocused helium-neon laser) is used.

With deep forms of endotoxicosis (subcompensation or decompensation of detoxification systems) intracorporal methods are ineffective. It is necessary to supplement them with extracorporal detoxification with taking into account the mechanism of action and therapeutic effect. With this purpose, the methods of clearance of the blood (hemosorption), plasma (plasmosorption), lymph (lymphosorption) by passing it through columns with coal sorbents are widely applied. Plasmapheresis is effective enough — division of blood into uniform elements and plasma with the following injection of uniform elements and donor plasma instead of removed toxic ones. With acute hepatic insufficiency, haemosorption, lymphosorption, plasmosorption, plasmapheresis are indicated, which model to a certain extent the detoxification function of the liver. With renal insufficiency, haemodialysis with the application of “artificial kidneys” is applied. Thus, the blood is cleared from low-molecular compounds with the help of selective diffusion through membranes made of cellophane, cellulose, and other materials. Azotemia is reduced, infringements of acid-base balance is corrected. The haemodiafiltration method is even more effective, during which two processes unite — dialysis with the removal of low-molecular compounds (urea, kreatinine) and haemofiltration with the removal of medium molecular compounds. Haemofiltration is a way of clearance through semipermeable membranes by convection due to high transmembrane pressure.

The given methods of detoxification with the application of photodynamic therapy (ultra-violet blood irradiation, intravascular laser irradiation of blood) are supplemented. Methods of tissue hypoxia correction with hyperbaric oxygenation (HBO) in pressure wards received wide application.