WOUNDS

Wound (vulnus) — is the mechanical injury to the integrity of the skin or mucous membrane. Wounds belong to the most often injuries in war and peace time. The problem of wounds treatment is one of the main and according to its condition the conclusion about the level of medicine development is made.

The clinical picture of a wound is determined by local (infringement of the integrity of tissue, gaping of wounds, bleeding and pain) and general attributes (acute anemia, shock, infection).

There are different classifications of wounds. After the character of a damaging agent the following kinds of wounds are distinguished:

Cut wounds — caused by a sharp object, linear-shaped andcharacterized by gapes, even edges and plentiful bleeding.

Chopped wounds — caused by a sharp massive object such asa sabre, axe and unlike to incision wounds they are accompanied by contusion and smashing of soft tissue.

Contused wounds are caused by a blunt object or occur duringa fall and the compression of tissue, characterized by uneven jagged edges and significant damage of the surrounding tissue.

Smashing and lacerated wounds are characterized by necrosisof soft tissue, frequently infected, insignificant bleeding.

Pricked wounds result from a prick by a sharp object, damageto soft tissue is insignificant, but because of the depth the vital organs can be injured — the heart, the large vessels, the lungs.

Gunshot wounds are the result of the actions of a bullet ormissile splinters; frequently accompanied by injury to large vessels, nerves, vital organs, thus the combination of two damaging factors is observed: mechanical and thermal; heavy forms of purulent, anaerobic infections frequently develop in fire wounds.

Bitten wounds are the result of human or animal bites, it frequently suppurates; animal bites can cause rabies or rat illness.

Poison wounds form as a result of poisonous snake or scorpionbites or poisonous military substances entering the wound or industrial poisons.

Excoriations and scratches are the most superficial damage totissue, and have a favorable course.

Mixed wounds are wounds which had influence of poisonousmilitary substance or radiation; radiation trauma is frequently combined with the radiation illness development.

After the reasons of damage the wounds are divided into operational and accidental. Depending upon the cavities of the body the wounds are divided into penetrating and non-penetrating (with or without damage of internal organs). After the anatomic features the wounds are subdivided as follows: wounds of soft tissue, the wounds with damage to vessels, nerves, tendons, internal organs. After the number of damages to one patient wounds are divided into single and multiple. Damage to several organs bordering two or several anatomic sites are considered as combined trauma.

It is possible to classify wounds by their anatomic localization: wounds to the neck, head, hips, thorax, stomach, etc.

The spreading of wounds according to the extent of infection has special value — aseptic and infected. Only postoperative wounds are considered as aseptic. Other wounds are considered infected, because at the moment of injuring the microorganisms could be on the skin or on the injuring object. The development of wound infections is accompanied by many clinical symptoms of general and local character. The earliest general symptoms are deterioration in the patient’s health condition and an increase in the body temperature. The character of the temperature curve depends upon the organism’s reaction and virulence to infections, massiveness of infection and abundance of the process, delay in pus discharge, occurrence of new purulent cells. Generalization of infection is accompanied by hyperthermia and a change in the character of the temperature curve. An important symptom is fever, connected to the massive entrance of microbes into the blood, their toxins and products of tissue disintegration. Fever testifies to the presence of un-drained purulent cells, the appearance of putrefactive infections or the septic condition of the patient.

The progressing of infection in the wound is accompanied by infringement of the function of the nervous system (headache, sleeplessness and inhibition), cardiovascular system (tachycardia, disturbances of the cardial rhythm), respiratory system (dyspnea, shallow breathing). Pulse acceleration with decreased body temperature is an adverse symptom which testifies of progressing infections in wounds and a decrease in immune protection. Infringements of the liver function (in particular desintoxication) and the kidney function (albuminuria, oliguria) are marked. The patient complains of dryness in the mouth, nausea. Changes of the general character are expressed to different extent. With mild forms of banal purulent infection in wounds they are insignificant, in severe cases the endotoxic shock, which can cause the death of the patient, develops.

Local changes in the wound depend both upon the degree of posttraumatic destruction of tissue and the activity of the microbic flora. The greatest changes are marked in smashing-lacerated wounds and gunshot wounds.

Usually a day after bacterial pollution of the wound, a pyoinflammatory process appears precisely. The bottom of the wound and its contents gets dirty-grey, the edges of the wound are dense and swollen. The skin under the hypostasis zone becomes hyperemic, hot when touched and painful during palpation.

Pain in the wound amplifies with infringement of discharge outflow (pulsating pain). The wound excretion, its color, smell, consistence, amount depend upon the kind of microbic agent. Necrotic tissue in the initial phase of inflammation is usually densely fixed to the bottom and edges of the wound, their amount during the adverse course of the process can grow due to secondary necrosis. Aggrevation of inflammation signs (pain, hypostasis, and hyperemia) are adverse prognostic symptoms and testify to the progress of a purulent process.

In case of a favorable wound process course, 3–5 days after the trauma, inflammatory demarcation of nonviable tissues, which then reject and lysed in the wound, occurs. At the same time, clearing of the wound from microbic flora takes place. The inflammatory reaction gradually ceases, the wound process passes into the period of reparation with clinical attributes of the granulation tissue appearance in the wound. Healthy granulations are bright-pink, their surface is glossy, easily bleeds with insignificant damage. Infiltration of the edges of the wound is considerably reduced, discharge from the wound, which becomes serous, decreases. Granulation tissue is the morphofunctional barrier (granulation roll), created on the wound site against harmful environmental influence. Healthy granulation tissue prevents the penetration of infection, diffusion of toxins and products of tissue disintegration, limits the loss of proteins and ions.

Disturbance of the character of granulations (languid, cyanotic or grayish-red), decrease in their growth, and increase in the amount of wound discharge are extremely adverse signs. They are evidence of the activation of primary wound florae or the presence of superinfection, as well as a decrease in the immune status. The probability of generalization of infection (sepsis) is not excluded. Clinical picture of damage of the granulations barrier function is in increase in the volume of the local inflammatory process with a renewal of pyoresorption fevers (deterioration of health condition, increase of pain in the wound, left shift leukocytosis, lymphopenia, increase in the leukocytic index of intoxication, acceleration of the erythrocyte sedimentation rate — ESR).

In order to choose the correct treatment policy of wounds, the surgeon should correctly estimate the character of damage, phase of the wound process. The wound process is a set of biological phenomena which consistently develop in the wound. The pathogenesis of the wound process depends on the phase-like course, unity of individual phases and transition of one phase into another one. Despite the fact that numerous works are devoted to the study of the wound process pathogenesis, a standard classification of the wound process is not established yet. The most widespread ones are the following.

For a long time in clinical practice I. G. Rufanov’s (1954) classification prevailed. According to this classification the wound process course consists of two phases:

I phase (phase of hydration) — transition of gel into sol, cleansing of dead tissue from the wound;

ІІ phase (phase of dehydration) — granulation, tissue regeneration.

For the last years among clinical physicians the most popular is G. I. Kuzin’s classification (1977), according to which three basic phases of the wound process course are distinguished.

I phase — inflammation, subdivided into two periods — the period of changes and period of purification of the wound from necrotic tissue;

ІІ phase — regeneration or proliferation — granulation tissue formation;

ІІІ phase — reorganization of the scar.

The first phase of acute inflammation, or hydration, is characterized by hyperemia of the wound tissue, blood vessels dilating and their permeability disturbances. Stasis and thrombosis in vessels are observed. Tissue is saturated with liquid, there is much wound discharge.

Metabolism disorder is observed in the wound, processes of aerobic and anaerobic glycolysis prevail. As a result, the amount of insufficiently oxidized products of metabolism (lactic, pyroracemic acid) increases in the wound, acidosis occurs. There is a relative reduction in the amount of calcium, but the amount of potassium, carbon dioxide as well as tissue hypoxia increases.

Leukocytes and phagocytes migration amplifies; the release of necrotic tissue, toxins and disintegration products begins. This is promoted by the phagocytal and fermental activity of cells. Autoand heterolyzates also take part in the autolysis processes. Clinical changes are observed in the wound: pain, swelling, infiltration, rise of temperature, infringements of organ functions.

In the second phase — regeneration — regenerative processes prevail, exudatation is reduced. Therefore this phase is also called dehydratation.

Blood circulation improves in tissue and the contents of oxygen increases, hydroxyl ions and calcium increase, the amount of hydrogen ions and potassium decreases.

Therefore metabolism is normalized and acidosis is reduced. The opening of the wound is filled with young connective tissue; cicatrix starts to form. With the beginning of dehydration, the pain, temperature, swelling and infiltration decrease. The wound is cleansed from wound discharge and necrotic tissue, granulation tissue is formed in it and there are attributes of epithelization of the wound edges. Clinically these phases are divided one from another not so precisely. It is possible to observe frequently the processes characteristic for both phases. However, the prevalence of a corresponding process allows a clinical physician to verify the phase and appoint corresponding treatment.

Any damage to the tissue causes a complex of biochemical reactions both in the wounded cell and in different organs and systems of the entire organism.

The basis of metabolism of the wound process is infringement of metabolism, resulting from a trauma. The earliest display of reaction to a trauma is an increase in the permeability of capillaries, which enables albuminous components of plasma to penetrate into the intravascular space, which causes infiltration of the injured tissue and blockade of nutrients and oxygen entering into the intercellular space and cells. Therefore, the earliest infringement of metabolism in the wounded cell is the transition to anaerobic type of glucose decomposition.

In early phases there is a decrease in the respiratory factor, increase in anaerobic glycolysis and autolysis of tissue. Anaerobic glycolysis is the energy source, necessary for developing wound inflammations, processes of biosynthesis, connected to regeneration of cellular elements and tissue. Thus glucose is actively used and lactic acid collects, therefore there is acidic shift (pH). An increase in acidity in the wound is caused not only by the increase in formation of lactic acid and other organic acids of the Krebs cycle, but also the congestion of blood circulation in the dilated vessels which causes the congestion of carbonic acid.

Under the conditions of an acidic medium tissue exchange is broken, osmotic pressure increases, the activity of fermental processes changes. With acidic reaction bactericidal properties of tissue colloids moderately increase. A significant decrease in рН, connected with intensive infectious-inflammatory process in the wound, gets a negative value — vital activity is broken and cells die.

The development of wound inflammation and the damage of tissue results in the accumulation of potassium in tissue. An increase of the contents of potassium in the wound exudate, lymph and blood results in the infringement of the normal ratio of electrolytes (sodium, potassium, calcium). A certain relation between the growth of the concentration of Н-ions, potassium ions and the intensity of pyoinflammatory process is marked. When the inflammation starts decreasing, the contents of potassium, sodium and chlorides decrease, and the concentration of calcium increases. For each phase of the wound process, an increase in the activity of certain groups of enzymes, specific to the certain period of healing, is typical. For example, the phase of wound inflammation begins because of vascular reaction, during which vasoactive substances increase including proteolytic enzymes.

The level of vasoconstrictor substances (dofamine, noradrenaline, adrenaline, kinin) is regulated by transferase, and their surplus is neutralized by monoaminooxydase.

Approximately 6–9 h after damage to the central zone of the wound focus necrotization of tissues and cells, the early attribute of which is the reduction or disappearance of enzyme activity, begins.

An increase in enzyme activity in the wound occurs not only due to the activation of enzyme systems, but also as a result of increase of enzymes concentration, which come from blood plasma, migrating leukocytes and local cellular elements. A great amount of enzymes, which promote the destruction and removal of components of tissue disintegration from the wound release from granules in the extracellular space with the destruction of neutrophilic leukocytes. At the same time, in one-nuclear cells the high activity of glucose-6phosphate dehydrogenase is marked, which is the initial stage of the pentosophosphate cycle, connected with phagocytosis and the antibacterial action of oxidizing reactions. The regeneration phase begins with the epithelium cells migration. Energy for this process to a certain extent depends upon the ATPase enzyme activity. The mitotic reaction is always preceded by the activation of DNA synthesis. An increase in mitotic activity is accompanied by an increase of oxidation in the citric cycle with the participation of oxidoreductase. The fibroblasts, responsible for the synthesis of polysaccharides and collagen, have the maximal activity in the regeneration phase.

In the reorganization phase (formation of a scar), which begins approximately on the 12th–14th day of the wound process, the activity of the majority of enzymes is reduced, and then completely stops. Thus, changes in metabolism during the healing process are expressed by different types of enzyme reactions of catabolic and anabolic character.

Clinical picture classification of the wound process bases on the clinical criteria, which reflect the essence of each phase (B. M. Datsenko and co-authors, 1995). According to this three consecutive phases: purulent-necrotic, granulation tissue, new epithelium are distinguished.

Wound healing is a regenerative process that reflects the organism’s reaction to trauma. Healing process is influenced by many factors.

Wound regeneration is slowed down as a result of damage to blood vessels and nerves, the presence of blood clots and foreign bodies, necrotic tissue, due to development of virulent microflorae. General factors influence negatively the healing process: insufficiency of the liver and renal function, hypovitaminosis, diabetes, deficiency of organism’s immune protection.

There are two kinds (primary strain and secondary strain) of healing.

The following conditions are necessary for primary healing: smooth viable wound edges, their dense cohesion, absence of foreign bodies in the wound, necrosis cells and microflora.

Secondary healing is observed when there are no conditions for primary healing: presence of necrosis of the wound edges, gaping, clots, and foreign bodies. Wound microflora plays an important role. Secondary healing is characterized by pyesis and granulation tissue formation. In the phase of acute inflammation, or hydration, processes of alteration prevail in the wound, suppuration takes place. The wound is filled with pus, the edges are swollen, hyperemia, there are cells of necrotic tissue, only single sites of granulation, which appear basically on the 3rd, sometimes 8th–10th day are observed.

Pus is inflammatory exudate, which contains neutrophilic leukocytes, bacteria, remains of destroyed cells. Depending upon the kind of microflora the color, consistence and amount of purulent excretion change. For wound treatment the bacteriological investigation of the purulent exudate (release of clean culture and definition of antibiotic sensitivity to microflora) have great value. A significant amount of granulation tissue usually appears in the second phase — during regeneration (dehydration). Its formation is predetermined by an increase in the growth of blood capillaries, which, reaching the wound edges, don’t connect like with primary strain healing, but form loops. In the loops of capillaries, fibroblasts are placed, which due to intensive division, produce collagen fibers. At the same time epithelizaiton of the wound edges occurs.

Six layers are distinguished in the granulation tissue at histologic exam. The superficial leukocytic-necrotic layer contains leukocytes, cellular detritis and microbes. Under this layer, the layer of vascular loops is located, where there is a significant amount of polyblasts and collagen fibers. The third layer is the layer of vertical vessels (fibroblast, amorphous intermediate substance). The following three layers: maturating layer, layer of horizontal fibroblasts and fibrous. The basis is the layer of the mature fibrous connective scar. The granulation tissue is a barrier that separates the internal medium of an organism from external influence. It is very sensitive, weak mechanical trauma (rubbing by a gauze tampon) causes its damage and bleeding.

At the third phase of healing there is reorganization of the connective tissue scar (fibrosis tissue) and processes of epithelizaiton and healing come to an end.

With secondary healing a wide and uneven scar is formed. Sometimes it becomes keloid-dense, thickened, painful, gets red. The reason for keloids formation is neutrophic and endocrine disorders, insufficiency of local blood circulation. Frequently ulcers, which do not heal for a long time and can become malignant in some cases, develop on the keloid scar.

A number of methods of objective estimation of the wound process course are applied in the clinical practice. A change in the sizes of the wound can be supervised by planimetric methods. The sizes of a wound are measured with the help of sterile cellophane which outlines its contours (L. M. Popova’s method) or polyethylene (T. P. Ziryanov’s method). Bacteriological control over the course of the wound process is obligatory and includes the determination of the kind of pathogenic organism, its sensitivity to antibiotics and quantitative estimation.

The simplest method of determining the pathogenic organism with the help of bacterioscopy in smears-prints of the wound exudate with the coloring by Romanovsky—Gymsa. To get a full idea of microorganisms in the purulent wound, it is necessary to investigate not only the prints but also to make inoculation of the medium. It makes possible at the same time to identify deep microflora and determine the amount of pathogenic organisms in 1 g of tissue (level of bacterial insemination).

The level of bacterial insemination in the wound is a very important parameter in the doctor’s practice because it allows to objectively estimate the qualities of surgical treatment, make prognosis of the course of the pyoinflammatory process, control the terms of putting in secondary stitches, conduct comparative estimation of the efficiency of different medicamentous means, which are applied for the local treatment of wounds. As a rule, effective surgical treatment of the wound results in a decrease in the level of bacterial insemination of the wound (102–103 by 1 g of tissue). The increase in the amount of bacteria in the wound (105–106 by 1 g of tissue) is an adverse sign and testifies to sepsis development.

In order to determine the antibiotic sensitivity of microflora, usually a disk antibioticogram inoculation on the Petri’s cup with agar with the following application of standard paper disks moistened with solutions of different antibiotics are used. Microbes are considered resistant to the examined antibiotic if the zone of growth inhibition is less than 15 mm, sensitive — if the zone of inhibition is from 15 up to 25 mm and highly sensitive if this zone is over 25 mm.

Cytologic exam of the wound exudate has an important diagnostic value and characterizes the changes in the structure of cellular elements of the wound exudate depending upon the phase of wound process and the character of healing.

Clinically, the method of wound prints according to G. P. Pokrovska — M. S. Makarov and the method of superficial biopsy of the wound according to G. F. Kamayev are widespread. Both microflora, and cellular elements (leukocytes, connective tissue cells, and epithelium and the character of phagocytosis in the wound are taken into account in the cytogramm. Other methods are applied to study the wound process: the method of color thermography, the polygraphic method of defining partial pressure of gases, the electrothermometry method, the method of exam of wound electropotentials, the ultrasonic echolocation method. With the help of the echolocation method it is possible to determine the stage of inflammatory process. The quantitative methods of controlling the course of the wound process allows to objectively estimate different techniques of purulent wounds treatment.

Treatment of wounds is carried out with taking into account the biological processes, which take place. The purpose of treatment is to renew the primary form and function of the injured organs and tissue. The treatment of aseptic and purulent wounds is different. When treating aseptic wounds, the main demand is rest for the injured site and preventive measures of entering and developing an infection (painting the edges of the sutured wound with solutions of iodine, iodonatum, jodopyronum, spirit and closing it with a sterile gauze bandage, it is possible to apply antiseptic aerosols which harden on the wounds as a covering). With extensive postoperative wounds in order to stop lymphorrhea and bleedings in the opening in some cases active drainage of the wound is applied (according to Redon or the three-ampoule system).

All accidental wounds are infected. First aid for infected wounds consists of applying aseptic isolating bandage for preventive measures of subsequent infection during transportation, stoppage of bleeding (compression bandage, applying a tourniquet and the use of antishock actions — introduction of analgetics, drugs). Specialized help for these wounds consists of an operation with primary surgical debridement of the wound (PSD) within first 48 h after the injury. The best results of PSD are conducted during the first 8 h after the injury.

Theoretically and experimentally carrying out PSD was proven by O. O. Tcharukovsky (1836) and P. Fridrikh (1898). The purpose of PSD is to prevent the wound infection and create favorable condition for healing by transforming any wound into a incised wound and its suturing for primary healing. PSD can include the following components: toilet of the wound, suturing of the wounds, removing nonviable tissue, removing foreign bodies, haemostasis, and renewal of broken anatomic tissue interrelations. The terms for performing PSD have essentially great value; it should be executed as soon as possible. Depending upon the term of the PSD performance it can be: early — the first day after the wound, delayed — the second day, and late — after 48 h. After treatment of the operational field and anaesthesia, the edges, walls and bottom of the wound they incise with a scalpel; remove all damaged tissue, foreign bodies, rags, bone fragments and clots of blood which are free. After incision off the polluted and necrotic tissue, tools and gloves are changed, careful haemostasis and suturing the wound by layers is conducted.

PSD on different sites of the body have different peculiarities. They do not incise the vessels, nerves, or periosteum. They spare the muscles as much as possible, deleting only nonviable sites (dark, which do not contract with irritation by tweezers, do not bleed). It is necessary to be careful when treating damaged tendons. Joint cavities are closed. It is necessary to drain the wounds, especially the deep ones. Late surgical debridement (after 48 h) consists in simple cleansing the wound from dirt, pieces of the object which wounded, foreign bodies and removal of necrotic tissue. They do not incise the tissue within the limits of healthy sites. They incise and drain recesses, infected hematomas and abscesses, provide conditions for drainage of wound discharge.

Closing the wound and renewing the broken anatomic interrelations completes PSD. Depending upon the terms of conducting operation, there are different kinds of placed suturs. If PSD is carried out during the first 8 h after the trauma, primary suturs are imposed. The wound should be closed starting with the deep layers in order not to form free cavities, where excretion can accumulate. At suturing of deep wound it is necessary to enter a rubber or polyvinylchloride tube into it for antibiotic lavage and whenever possible create active aspiration of the wound discharge (rubber bulb, etc.). With late terms of carrying out PSD (after 24–48 h) and the presence of contraindications concerning placing primary sutures (danger of developing anaerobic infections) a retention suture is placed or they solve the problem about placing delayed sutures — primary or secondary sutures.

The primary delayed suture (tied or retention suture) is imposed on 3rd–5th day after PSD if there is no wound abscess.

Early secondary sutures are placed with the presence of infectious complications in the wound in 8–15 days with the disappearance of inflammation, the development of granulation tissue. They are placed on a granulating wound without incising the granulations.

Late secondary sutures are placed in later terms (15–25 days) when there is granulation and scar tissue, and the healing of wounds occurs slowly. Incision of the edges of the wound and the scar tissue of all depth (secondary surgical debridement) is carried out before suturing.

The principles of local treatment of purulent wounds should correlate with the stage of the wound process. In the first phase of inflammation (hydration) hypertonic solutions of different antiseptics, which have dehydration effect (10% solution of sodium chloride, 25% solution of glucose, 30% solution of urea, and 1–5% solution of boric acid) receive wide application.

Proteolytic enzymes (trypsinum, chymopsinum, chymotrypsin, terrilytin, elastomesenterasa, etc.), which have pronounced necrotic, inflammatory action, reduce antibiotic stability and virulence of microbes in the wound, also receive wide application. Last years, immobilized proteolytic enzymes (connected to the tissue matrix that gives an opportunity to create their constant concentration in a wound) are more widely applied. In order to fight with infection in the wound, antibiotics are applied with taking into account account the antibioticogram and sensitivity of a patient’s organism. It is necessary to prefer antibiotics which are entered directly into the wound (gramicidin, polymyxin, chloramphenicol, etc.).

With antibiotic-resistant strains, reserve antibiotics (cephalosporins, thienam, etc.) as well as such antiseptics as ethonium, chlorhexidine, rocal, dioxydine, sulfamilon, chlorophylipt, furagin, solaphur are usually applied last year. Water-soluble ointments with a polyethylene oxide basis — levosin, levomycol, dihydroxycol, 10% ointment of acetate mafenid, iodopionic ointment, haniphurin — meet the requirements of complex action in the first phase of the wound process. Polyethylene oxide forms complex compounds with antimicrobic preparations, increasing 20–60 times their action and providing their penetration into the depth of the damaged tissue. In the first phase medicamentous treatment is widely supplemented with physical methods of treatment: active draining the wound, laser therapy, treatment in gnotobiologic isolators, application sorption (carbon sorbents or non-tissue carbon materials placed on the wound), ultrasonic irradiation of wound, solux, diadynamical currents, magnetotherapy, ionophoresis with different antiseptics and regeneration stimulators.

In the second phase of the wound process, local medicamentous therapy should be directed on the stimulation of regenerative processes, protection of granulation tissue from damage and prevention of reinfection of the wound with hospital infection. With this purpose, vanillin, dogrose oil, ointment on a vaseline-lanolin basis with antibiotics, olasol-methyluracil ointment received wide application. It is possible to apply Vishnevsky ointment. Effective stimulators of the regeneration process are such preparations as combutecum, alginor. In the third phase of the wound process, the same therapy as for the second one is applied.

Medicamentous therapy prevails with the treatment of small wounds. With the treatment of large wounds, medicamentous therapy is combined with surgical treatment and modern physical methods.

While treating wounds, methods of general action on the organism in patients with endotoxicosis, infringements of the immune status and homeostasis have great value.

Immunotherapy of wound infection should be carried out according to concrete parameters of the immune status and should be directed on replenishing the deficiency of certain parts of immune protection.

Passive (replacement) and active immunotherapy are distinguished. The transfusion of fresh-citrate donor blood, introduction of hyperimmune plasmas (antistaphylococcal, anti-blue-pus), specific antibodies (antistaphylococcal, anti-blue-pus, anti-influenzal), bacteriophage, leukocytic mass, interferon are applied as replacement immunotherapy.

For active immunotherapy, the introduction of auto-vaccinations (made of wound microflora), staphylococcal anatoxin, different immunodepressants. As synthetic immunomodulating factors, levomysol (decaris), prodigiosan are applied. Natural immunomodulating factors, received from the thymus of an animal (tactivin, thymalin, thymogen, timosin) or from the bone marrow (B-activin or myelopeptide) are more specific.

Homeostasis correction is of great value — normalization of protein metabolism (high-caloric diet, protein preparations and blood substitutes, anabolic hormones).

For correction of endotoxicosis, which develops with generalized infection, methods of extracorporate detoxification of an organism, which neutralizes toxins in the blood or lymph, have recently received wide application. They are haemosorption, plasmosorption, plasmapheresis, lymphosorption. They are applied, basically, with hepatic insufficiency development. With acute renal insufficiency development against a background of wound infection, haemodialysis, haemofiltration, haemodiafiltration are applied.