Intensive Care of Emergency Conditions - V. M. Zaporozhan 2006

Endotoxemia and Detoxification Methods

The existence of endogenous intoxication stems from the very nature of critical states, which are accompanied by impaired METABOLISM and natural detoxification. Undoubtedly, it plays a significant role in the Pathogenesis of critical conditions. The main etiological factors and dominant secondary processes and reactions that serve as sources of endotoxemia (ET) are presented in Table 13.

Differentiating ET based on its underlying causes is valid only in the Cytology/cytology/16.html">Early stages of the process. The cascade of secondary reactions in the later stages of ET shares common features—whether in cases of impaired detoxification function, tissue damage (including the Skin), trauma, ischemia, infection, or immunosuppression.

Although it has been proposed to classify ET according to its pathogenesis into regenerative (impaired elimination of end metabolites), metabolic (accumulation of intermediary products of altered metabolism), resorption (absorption of breakdown products), and infectious (absorption of microbial toxin breakdown products), these primary mechanisms may recede into the Background as critical states progress, giving way to a complex of secondary reactions.

The underestimation of The Role of ET in critical conditions can be attributed, to some extent, to the lack of reliable diagnostic tools for this syndrome. In the late 1980s, research on ET was conducted at the Department of Anesthesiology and Intensive Care of the Odessa Medical University. The METHOD FOR DETERMINING the concentration of acid-soluble Blood Plasma fractions (A. S. Vladyka, 1987), quantified using N. I. Gabrielyan's screening method (1981), proved to be informative, simple, and accessible.

Class="center">Table 13 Factors contributing to The Development of endotoxemia (according to M. O. Belyakov, 1994)

These fractions are widely known as "middle molecules" or middle-molecule substances (MMS), which include oligopeptides and Polysaccharides—intermediate products of protein and other Types of Metabolism. A statistically significant increase in the levels of these ET markers, correlating with disease severity, has been detected in all types of critical conditions, but is most pronounced in patients with impaired vital functions (hemodynamics and gas exchange) and natural detoxification and excretion mechanisms (liver, kidneys, lungs, gastrointestinal tract, macrophage-phagocytic system, skin).

Staff members of the Department (M. P. Yuzvak et al., 1994) also established that disease severity and MMS concentration correlate with elevated levels of thermostable Proteins and a significant imbalance between The activity of proteolytic enzymes and their inhibitors. This confirms the presence of ET across all forms of critical illness, including shock. Consequently, this suggested the existence of a "shock protein," the dynamics of whose concentration can be used to judge the stages of primary hypovolemic shock (compensated, reversible decompensated, and irreversible).

However, this list by no means exhausts the chemical diversity of endotoxins. They also include biogenic amines, regulatory Peptides, Components of the kallikrein-kinin cascade, intermediate and final products of coagulation and Fibrinolysis, peroxidation processes, complement system components, lysosomal enzymes, other metabolic products, and Bacterial toxins. Moreover, the issue is not only an increase in endotoxin concentration but also alterations in the ratios among specific constituents. A toxic effect can easily be triggered simply by a decrease in inhibitor activity, which is characteristic, for example, of Lipid Peroxidation or the kallikrein-kinin cascade.

Based on their MECHANISM OF ACTION on effector organs, Cells, and subcellular structures, endotoxins can be divided into groups with direct, indirect, and mixed effects.

A typical example of direct-acting endotoxins is inflammatory mediators that induce SIRS, although these mediators themselves appear in response to bacterial toxins (whether from live or dead Bacteria, indistinctly) during sepsis or As a result of the absorption of tissue breakdown products, including necrotic skin lesions.

The aforementioned bacterial toxins and breakdown products can serve as Examples of indirect-acting endotoxins—operating via inflammatory mediators.

Mixed-action toxins can be considered substances within the middle molecule pool, whose targets simultaneously include the BLOOD COAGULATION SYSTEM, vascular walls, smooth Muscle elements, Cell/35.html">Mitochondria, Lysosomes, and other structures upon which MMS exert their effects either directly or through the involvement of secondary mediators.

According to their effects on cellular structures, endotoxins can be classified as those with cytopathic effects; activators of lysosomal enzymes; blockers of mitochondrial Bioenergetics; initiators of free-radical processes; and inhibitors of ribosomal Protein Synthesis.

At the interorgan and intersystem level, endotoxins are categorized into activators of complement, white Blood Cells, the kallikrein-kinin system, coagulation, and fibrinolysis, as well as substances that alter smooth muscle tone, transendothelial transport, and Inducers of blood cell aggregation.

Defective blood cells, immune complexes, IMMUNOGLOBULINS, antigens, and other components slated for elimination can be provisionally classified as toxins.

Methods for managing ET are quite diverse. While emetics, diaphuretics, Diuretics, laxatives, enemas, and bloodletting have been known for millennia, most Methods of artificial detoxification emerged and gained professional recognition In the second half of the 20th century, and new ones continue to be developed.

They can be classified into methods that support or enhance natural detoxification and methods of artificial detoxification. Depending on the Body Fluids being purified, they may involve the depuration of: Blood and Its components; lymph and other biological fluids; chyme; or wound surfaces.

Below is a description of various detoxification methods, systematized by their purification mechanism (M. O. Belyakov, 1994, with addenda).

1. Infusion therapy—administration of albumin and artificial plasma expanders that sorb toxins onto The surface of their molecules and eliminate them alongside The excretion of these substances.

2. Exfusion methods—traditional bloodletting, exchange transfusion, as well as lymph drainage, bowel and renal stimulation (Forced diuresis), juice, Bile, and sweat elimination (which retain their efficacy), and colon hydrotherapy, which is currently gaining ground.

3. Membrane methods

3.1. Hemodialysis (so-called standard hemodialysis)—a method of extracorporeal blood purification via dialysis across a semipermeable membrane that separates the Blood Circulation system from the dialysate flow system within the dialyzer. The primary indication for hemodialysis is endotoxemia caused by acute or chronic renal failure.

3.2. When it is necessary to reduce hyperhydration, hemodialysis is performed in an ultrafiltration mode by establishing a hydrodynamic or osmotic pressure gradient in the dialyzer. Ultrafiltration typically removes 2–3 liters of fluid per dialysis session, which practically corresponds to the volume accumulated between consecutive dialysis sessions.

3.3. Hemofiltration—a method of extracorporeal blood purification through filtration across a membrane with high hydraulic permeability (so-called high-flux membranes) driven by a transmembrane pressure of approximately 200–500 mm Hg. The filtration rate is 2–4 liters per hour. The 25–28 liters of fluid removed per session are almost entirely replenished with electrolyte solutions. The indications are the same as for hemodialysis. While hemofiltration lags behind hemodialysis in the efficiency of urea, creatinine, and uric acid clearance, it surpasses it in reducing middle-molecule levels.

3.4. Hemodiafiltration is a combination of standard hemodialysis and hemofiltration, which achieves the same blood purification in half the time. It is performed using a dialyzer membrane with high Water permeability.

3.5. Peritoneal dialysis is a method of extracorporeal extracorporeal blood purification in which a sterile dialyzing solution is introduced into the peritoneal cavity in portions or continuously via a fistula in the anterior abdominal wall. The Peritoneum serves as the dialyzing membrane, through which approximately 1200 mL of blood circulates per minute. The urea clearance of modern peritoneal dialysis is not inferior to that of hemodialysis, and it outperforms hemodialysis twofold in terms of middle molecules. Indications for peritoneal dialysis include childhood or advanced age, the impossibility of vascular access for hemodialysis, and the presence of peritonitis. Absolute contraindications include infection or skin lesions of the anterior abdominal wall; relative contraindications include hypercatabolism, obesity, recent abdominal surgery, peritoneal adhesions, respiratory failure, and hernias.

3.6. Intestinal dialysis involves the administration of a dialyzing solution through a tube inserted as high up into the Large Intestine as possible, similar to high siphon enemas. Its efficacy is inferior to other mentioned dialysis methods.

3.7. Bronchoalveolar lavage is the administration of a dialyzing solution through a catheter passed via a double-lumen endotracheal tube into one of the main bronchi. It is very rarely used clinically.

3.8. Membrane plasmapheresis is the removal of blood plasma from the body by separating blood through a membrane plasma filter. The core Structure of a plasma filter is a membrane that allows fluid to pass while retaining the globular fraction of blood. The main condition for the plasma filter's operation is transmembrane pressure, i.e., the difference between the hydraulic pressure before the membrane (usually +100 mm Hg) and after it (usually -70 mm Hg). To prevent plasma filter thrombosis, heparin at 150 IU/kg and Glugicir, which contains sodium citrate, are injected into the bloodstream system before the filter at a 1:9 ratio relative to blood flow. Hypocoagulant doses vary depending on the patient's coagulation potential: they are increased in case of a hypercoagulability tendency and decreased in hypocoagulation. With normal coagulation potential (prothrombin 90%, fibrinogen 40 g/L, platelets 250 thousand), hemodilution is not required, but it is necessary if these values are elevated. Typically, 30% of the blood flow or 50% of its liquid fraction is filtered. Consequently, blood exits the plasma filter with a hematocrit of 55–60%. If the hematocrit reaches 65–70%, There is a risk of damaging the thickened blood within the filter collectors, lines, and cannula. Plasma loss replacement (1:1) occurs simultaneously or with some lag using crystalloids, colloids, and, for significant volumes, donor plasma. It is important to bear in mind the potential development of homogeneous plasma syndrome with massive plasma replacement volumes (antihistamines, calcium salts, and corticosteroids are administered prophylactically). There are 4 methods of membrane plasmapheresis:

— automated double-needle using roller pumps;

— automated single-needle using the Gemos-PF device, etc.;

— non-automated — blood is drawn and passed through the plasma filter under the force of gravity;

— syringe-based — for newborns and infants.

3.9. Cascade Membrane filtration is filtration through several sequential filters.

4. Gravitational methods — gravitational plasmapheresis, in which the liquid fraction of blood containing toxic components is removed from the body under The Influence of gravity or centrifugal force.

Unlike hemodialysis, plasmapheresis allows for the differential removal of specific components—ranging from globulins and Lipids to blood cells—making it a leading and effective Treatment modality either as a primary or adjunctive therapy. Furthermore, due to the replacement of 1–3 L of plasma per session, a new metabolic environment is established. Consequently, changes affect virtually all blood components—electrolytes, proteins, hormones, regulatory peptides, the glycocalyx, erythrocytes, cellular receptor apparatus, etc., which inevitably impacts cellular arrays, organs, and body systems.

Gravitational plasmapheresis can be performed either by sedimentation or centrifugation of a drawn portion of blood in containers (preferably plastic bags), followed by plasma removal and the return of formed elements to the patient, or via continuous plasmapheresis in a special centrifuge connected to two of the patient's Blood Vessels. Blood is drawn through one vessel and formed elements are returned through the other, while the centrifuged plasma is removed from the system via an outflow line.

Distinct from membrane and gravitational methods is plasmapheresis in which thawed blood cellular elements are returned to the patient while frozen plasma is discarded.

5. Sorption methods

5.1. Hemoperfusion is an extracorporeal detoxification method involving the perfusion of blood through a Column containing a sorbent (activated charcoal or ion-exchange resins), where toxic elements are bound either On the surface via adsorption or throughout the entire volume via absorption.

Indications for hemoperfusion include endogenous intoxication of various origins—diseases and lesions of tissues and organs, including the skin, sepsis, allergies, radiation sickness, etc.

While numerous methods of blood perfusion through a column exist, pumps are predominantly used, with roller pumps being the most common.

The system is usually connected to central Veins using percutaneous catheters inserted via the Seldinger technique. However, if hemoperfusion is performed on patients who already have an arteriovenous shunt or fistula established for hemodialysis, the sorption column is connected via those devices, and perfusion is driven by the hemodialysis machine's pumps.

5.2. Plasmasorption is the purification of plasma by perfusing it through a column containing a sorbent. For this purpose, the column is either integrated into a continuous plasmapheresis system or plasma collected during intermittent plasmapheresis is passed through the column and subsequently returned to the patient intravenously.

5.3. Lymphosorption is the purification of lymph by perfusion through a sorbent column. An external drainage of the Thoracic duct is surgically established, collecting from 200 to 5000 mL of lymph per day. As it is collected, the lymph is perfused through the sorbent column, and the purified product is returned intravenously.

5.4. CEREBROSPINAL FLUID sorption (liquorsorption) is the purification of cerebrospinal fluid by perfusing it through a sorbent column. Clinical experience remains limited due to technological difficulties associated with the need to drain the spinal canal and Brain ventricles.

5.5. Enterosorption is a method of binding (via adsorption, absorption, Ion Exchange, or complexation) and eliminating endogenous and exogenous toxic substances, supramolecular structures, and cells from the gastrointestinal tract. There are about a hundred types of sorbents: carbon-based, silica gels, zeolites, alumina gels, aluminosilicates, oxide and other natural sorbents, organic polymers, organomineral, and composite Materials. They are administered orally into the gastrointestinal tract, via a tube (in pyloric stenosis, they are removed after a 15–25 minute exposure and a fresh portion is introduced), or via enema into the large intestine. There is no single universal recommendation for sorbent dosage and administration frequency, as optimal efficacy depends on both the type of sorbent and The Nature of the pathological process. Indications for enterosorption include various endogenous intoxications, particularly those associated with skin diseases.

5.6. Vulnerosorption is the treatment of wounds using local sorbent application. The sorbent is applied either through a layer of gauze or directly onto the wound, or, in the case of wound cavities, in the form of Mikulicz packs.

5.7. Immunosorption is hemoperfusion using immunosorbents that feature surface-fixed antigens, thereby enabling the selective sorption of specific Antibodies (A. G. Chuchalin, 1989).

6. Xenoperfusion: detoxification methods involving the perfusion of xenoorgans (from the Greek xenos meaning "alien") or their specific elements.

6.1. Liver perfusion (with the pig's liver proving to be the most effective) — despite thoroughly flushing the vascular bed prior to connection — yielded results that fell far short of expectations due to immune incompatibility, which led to rapid microcirculatory blockage in the liver, reduced volumetric blood flow, and the development of organ edema. Liver slice perfusion (A. E. Borisov et al., 1976) and isolated hepatocyte perfusion (G. E. Ostroverkhov, 1975) proved somewhat more productive.

6.2. Renal perfusion was limited to just a few tens of minutes for the same reasons and proved ineffective.

6.3. Lung perfusion. Canine lungs were connected to a patient's blood vessels to correct gas exchange and metabolism (S. O. Symbirtsev et al., 1983); however, xenogeneic pulmonary edema developed within 1 hour.

6.4. Spleen perfusion was quite widely used for both detoxification and immunocorrection (V. I. Shumakov et al., 1985). It was later discovered that The Effect of perfusing minced spleen tissue, or infusing a recipient with an isotonic NaCl solution previously perfused through a whole or minced spleen, even surpasses the effect of whole spleen perfusion while avoiding numerous Technical Challenges.

7. Oxidative methods

7.1. Electrochemical oxidation is a method of bodily detoxification through The oxidation of toxins, mimicking the process that occurs in the liver with the participation of cytochrome P-450, a specialized detoxifying enzyme. Attempts at direct electrochemical oxidation have not progressed beyond the experimental stage. Indirect electrochemical oxidation involves subjecting an oxygen carrier solution—typically 0.89% NaCl—to electrolysis, which drives the following reaction:

NaCl + H₂O → 2е NaClO + H₂.

The resulting sodium hypochlorite is introduced into the bloodstream; being unstable in the presence of organic substances, it oxidizes them via the reaction:

RH + NaClO → ROH + NaCl.

In this manner, endotoxins are oxidized—such as bilirubin, ammonia, urea, creatinine, Cholesterol, CO, and uric acid—alongside xenobiotics including aniline, acetone, acetoacetate, ethanol, methanol, and others.

NaClO exerts a bactericidal effect on all species and groups of microorganisms without exception, including antibiotic-resistant strains.

NaClO for medical purposes is produced using an EDO device (electrochemical Organism detoxification), in which passing an electric current of 0.4 A/h through 100 ml of an isotonic NaCl solution yields NaClO at a concentration of 0.12% (1200 mg/L). When introduced into the bloodstream, this solution causes neither hemolysis nor shifts in other morphological and biochemical parameters, even upon repeated administration of the same dose after 1 hour.

7.2. Blood ozonation is a method of organism detoxification via the direct oxidation of toxins and the active effect of ozone on proteins, enzymes, and their inhibitors. This is driven by ultraviolet radiation energy contained within the ozone in the form of photons released when the gas enters the blood or lymph, thereby altering the activity of endogenous detoxification mechanisms. The effective therapeutic dose of ozone is 0.8–1.6 µg/L in physiological saline, administered intravenously at 100–200 ml per day. Indications for blood ozonation include Metabolic Disorders or endotoxemia in critical conditions such as post-resuscitation disease, shock, sepsis, renal failure, and Burns. Contraindications for blood ozonation include hyperthyroidism, increased bleeding tendencies, and ozone allergy.

7.3. Hyperbaric Oxygenation (HBO) involves the therapeutic application of increased air pressure with an elevated oxygen content within a hyperbaric chamber. Among HBO's numerous therapeutic pathways is its detoxification effect, which manifests as a reduction in lactate acidosis, the Prevention of toxic metabolite formation coupled with the activation of their neutralization, enhanced microsomal oxidation leading to the accelerated conversion of xenobiotics into less toxic substances, the uncoupling of carboxyhemoglobin, methemoglobin, and cytochrome c oxidase from toxic compounds, and the activation of antioxidant processes (P. M. Chuyev et al., 1999). Detoxification is further supported by bacteriostatic and immunomodulatory effects, as well as a reduction in the toxicity of certain therapeutic agents (such as corglycon and strophanthin).

7.4. Extracorporeal membrane oxygenation is a method of blood and oxygen oxygenation that takes place across a separating gas-exchange membrane. Its detoxifying mechanisms largely mirror those of HBO. Based on their design features, membrane oxygenators are classified as plate-type (e.g., "Most", "Sever", "Istok"), coil-type, or capillary-type. The technique for performing prolonged perfusions via membrane oxygenators differs from short-term perfusions during open-Heart surgery; it demands meticulous attention and more refined correction tools. Connection is predominantly carried out via a venoarterial approach. It is considered appropriate to perform this therapy concurrently with detoxification using sorbents and other devices (S. O. Symbirtsev, M. O. Belyakov, 1986).

8. Quantum methods

8.1. Ultraviolet blood irradiation (UVBI) is characterized by a broad spectrum of therapeutic effects, the efficacy of which depends on the dose, the spectral CHARACTERISTICS OF THE radiation, and the volume of irradiated (photomodified) blood. Ultraviolet rays are subdivided into UVC with a wavelength of 100–280 nm, UVB with a wavelength of 280–315 nm, and UVA; wavelengths up to 280 nm are termed short-wave, while those exceeding 280 nm are long-wave. Photon energy is inversely proportional to its wavelength. When interacting with Biomolecules, they absorb photons, triggering photobiological reactions at the cellular, systemic, and whole-organism levels. Shorter-wave UV rays (< 300 nm) predominantly induce destructive processes, whereas longer-wave UV rays (> 300 nm) drive regulatory (altering biomolecular and cellular activity) and restorative processes (repairing the Damage caused by short-wave UV radiation). These alterations affect the glycocalyx and cell membranes, leading to decreased cell aggregation and increased electrical potential. The release of biologically active substances from cells is stimulated, alongside the activity of Lysozyme, complement, antibodies, antioxidant defenses, lipid peroxidation (LPO), as well as procoagulant and anticoagulant activities, which are considered the triggering mechanism of UV therapy. Technically, ultraviolet irradiation can be performed both extracorporeally and intravascularly. Exfusion of blood exceeding 3 ml/kg of the patient's body weight is contraindicated. Side effects and complications include pyrogenic and allergic reactions, photodermatitis, thrombophlebitis at the sites of repeated (7–10) punctures in the same vein, and the exacerbation of latent Hypertension or hypotension.

8.2. Laser blood therapy does not fundamentally differ in its effects from UVBI (I. G. Dutkevich, A. V. Marchenko, 1994). It utilizes the monochromatic light of a helium-neon laser with a wavelength of 632–633 nm via intravascular blood irradiation.

9. Transplantation methods

Kidney transplantation is the most widespread approach today, alongside liver transplantation to a somewhat lesser extent, both of which are directly related to detoxification.

The search for optimal indications and contraindications for each of the aforementioned methods is ongoing. An example is the intensive care strategy for critical conditions, which takes into account the established patterns of endotoxemia development in these states and its impact on disease progression. Undoubtedly, one of the hallmark features of a critical condition is the disruption of hemodynamics and gas exchange. However, these disturbances may be either primary or secondary relative to endotoxemia (ET), and intensive care tactics largely depend on resolving precisely this question. In any case, measures to normalize Respiration and circulation must be undertaken immediately. Yet, whether it is advisable to promptly Supplement these with detoxification methods—and specifically which ones—depends on determining the underlying cause of the critical state and the pathogenesis of ET. Several scenarios are possible.

If the pathological condition does not cause serious disruption to the body's vital functions, PHYSIOLOGICAL AND BIOCHEMICAL constants remain within homeostatic limits, and the organism continues to function—albeit bearing a specific load aimed at resolving the pathology. Since life-support is maintained via self-regulation in this scenario, the condition of such patients cannot be classified as critical.

Therapeutic tactics are limited to etiological treatment, measures to improve the operating conditions of life-support systems, and monitoring vital functions to ensure that any onset of severe impairment is not missed.

When vital hemodynamic and gas exchange functions are compromised (as exemplified by various types of shock) alongside impaired tissue perfusion and the development of cellular Hypoxia and hypoenergies, metabolic disorders emerge in the form of hypercatabolism and accelerated endotoxin production. Prior to the onset of a "Shock Kidney" and the blockade of other elimination mechanisms, ET does not reach catastrophic proportions, although it significantly impairs self-regulation and the restoration of vital functions.

Etiopathogenetic and replacement therapy aimed at normalizing hemodynamics and gas exchange play a primary role in the treatment of these patients. Detoxification contributes to a more rapid restoration of vital activity. Since this category of patients typically does not experience an accumulation of water, electrolytes, and low-molecular-weight End products of Protein metabolism, but exhibits elevated levels of middle-molecule peptides (MMPs), both methods supporting or enhancing natural detoxification and hemosorption are suitable for managing endotoxicosis (ET).

Isolated Renal Dysfunction against the background of relatively preserved hemodynamic and gas exchange functions is characteristic of the uncomplicated course of chronic renal failure (CRF). It is accompanied by the accumulation of metabolic products, water, and electrolytes in the body, leading to acid-base balance (ABB) disturbances. Consequently, the Central Nervous system, respiration, and circulation are progressively suppressed. Without waiting for the severe disorders typical of the late stages of ET in "uremia," active detoxification should be initiated without any hesitation about starting too early.

The main method of detoxification is hemodialysis (as well as, depending on indications and technical capabilities, hemodialysis with ultrafiltration, sequential dialysis, hemofiltration, and hemodiafiltration). Hemosorption plays an auxiliary role by removing those toxins that are poorly dialyzable. Standalone use of hemosorption is ineffective here, as it cannot correct water-electrolyte balance and ABB.

The combined Impairment of Vital functions and natural detoxification—that is, multiple organ dysfunction syndrome (MODS), which is typical of ACUTE RENAL FAILURE (ARF) in the oliguric/anuric stage and the terminal stage of CRF—is accompanied by an interrelated and interdependent (vicious circle) disruption of all life-support systems. In this category of patients, ET is most pronounced, as it is caused by hypercatabolism, blocked elimination of actively generated metabolites, as well as the retention and accumulation of water and electrolytes in the body.

The therapeutic strategy in such cases consists of restoring vital functions using all modern intensive care techniques. Following hemodynamic stabilization, early

hemodialysis combined with hemosorption is recommended, and to eliminate tissue hypoxia, these can be combined with hyperbaric oxygenation (HBO).

Liver dysfunction can be of independent significance (e.g., in cirrhosis) or act as a factor increasing risk (e.g., hepatorenal syndrome). In all cases, A wide variety of clinical courses is possible. The most unfavorable among them is the progressive course, which leads to the loss of numerous partial hepatic functions and an increase in ET resulting from both metabolic disorders and impaired hemodynamics and gas exchange.

In the treatment of patients with hepatic failure in the early (I, II) stages, a combination of hemosorption and HBO is recommended. In the stage of hepatic coma, both of these methods have low efficacy.

According to our data, the timely inclusion of detoxification methods in the complex of intensive care increases the efficacy of treatment for critical conditions, reducing mortality from 50 to 37.5%.

References

1. Adamenko N. P. Zamestitelnye faktory domashnego metoda ozhivleniya [Replacement Factors of the Donor Resuscitation Method]. Kyiv: Zdorov'ya; 1981. 136 p.

2. Aksentyev S. A. Plasmasorption in intensive care. In: Dostizheniya i perspektivy sovremennoy anesteziologii i intensivnoy terapii [Achievements and Perspectives of Modern Anesthesiology and Intensive Care]. Dnipropetrovsk; 2003. p. 13.

3. Belyakov N. A., editor. Alternativnaya meditsina [Alternative Medicine]. St. Petersburg; Arkhangelsk: Severo-Zapadnoe knizhnoe izdatelstvo; 1994. p. 225-265, 299-336.

4. Beresnev A. V., Veligotskiy A. N., Siplyvyy V. A. The Use of biosorption in patients with peritonitis. Klinicheskaya khirurgiya. 1966;(2):9-10.

5. Vladyka A. S. Hemosorption in the complex intensive care of critical conditions. Visnyk Sumskoho derzhavnoho universytetu. 1996;(1):123-126.

6. Gusak V. K., Shano V. P., Miminoshvili O. I., et al. Vybor metoda efferentnoy terapii pri ozhogo shoke: Metodicheskie rekomendatsii [Choice of Efferent Therapy Method in Burn Shock: Methodological Recommendations]. Donetsk; 2002. 15 p.

7. Usenko L. V., editor. Gemosorbtsiya v kompleksnom lechenii endotoksikozov [Hemosorption in the Complex Treatment of Endotoxicoses]. Kyiv: Zdorov'ya; 1986. 256 p.

8. Korzh Yu. I., Snisary V. I., Oksenyuk V. I., et al. Hemosorption and plasmapheresis in the complex treatment of severe burn trauma in children. In: Dostizheniya i perspektivy sovremennoy anesteziologii i intensivnoy terapii [Achievements and Perspectives of Modern Anesthesiology and Intensive Care]. Dnipropetrovsk; 2003. p. 71-72.

9. Hromashevska A. L. "Middle molecules" as an indicator of "metabolic" intoxication in the body. Laboratorna diahnostyka. 1997;(1):11-16.

10. Gunina L. M. Markers of endotoxicosis and Methods of Detoxification Therapy. Bil, znebolyuvannya i intensyvna terapiya. 1998;(4):28-32.

11. Dolina O. D., Manuylov B. M., Skobelskiy V. B. Indirect electrochemical oxidation of blood in the complex therapy of pneumonia in critical conditions. Anesteziologiya i reanimatologiya. 1997;(3):52-56.

12. Shumakov V. I., Dmitriev A. A., Levitskiy E. R., et al. Iskusstvennye organy [Artificial Organs]. Moscow: Meditsina; 1990. 352 p.

13. Kondrashov V. I., Petukhov E. B. Ultrafioletovoe obluchenie krovi [Ultraviolet Blood Irradiation]. Moscow: Meditsina; 1997. 223 p.

14. Vladyka A. S., Belyakov N. A., Malakhova M. Ya., et al. Blood concentration and biological activity of middle-mass molecules in critical bodily conditions. Anesteziologiya i reanimatologiya. 1987;(3):41-44.

15. Maistrovskyi O. Y., Klihunenko O. M., Vasylchenko S. L., et al. Likuvalnyi hravitatsiynyi plazmaferez na aparati PF-05 z vykorystannyam bahatorazovykh rotoriv: Metodychni rekomendatsiyi [Therapeutic Gravitational Plasmapheresis on the PF-05 Apparatus Using Multi-Use Rotors: Methodological Recommendations]. Dnipropetrovsk; 1999. 17 p.

16. Luzhnikov, E. A., Goldfarb, Y. S., & Musselius, S. G. (1993). Ways to improve the efficacy of emergency body detoxification in acute exo- and endotoxicoses. Anesthesiology and Reanimatology, 1, 56-65.

17. Lopatkin, N. A., & Lopukhin, Y. M. (1989). Effector methods in medicine. Moscow: Meditsina.

18. Mikhailovich, V. A., Marusanov, V. E., & Bichun, A. B. (1993). Erythrocyte membrane permeability and erythrocyte sorption capacity as optimal Criteria for the severity of endogenous intoxication. Anesthesiology and Reanimatology, 5, 66-69.

19. Neimark, M. I., & Rogachevsky, P. L. (1993). A modified technique of blood perfusion through a xenospleen in patients with peritonitis. Anesthesiology and Reanimatology, 1, 23-25.

20. Nikiforov, Y. V. (1997). Gas exchange function of the lungs in patients with multiple organ dysfunction syndrome undergoing hemofiltration. Anesthesiology and Reanimatology, 5, 39-41.

21. Konovchuk, V. M., Akentiev, S. O., Kokalko, M. M., et al. (1998). Rationale for the efficacy and differentiated approach to intra- and extracorporeal detoxification methods in severe purulent-septic complications in surgical practice. Pain, Anesthesia and Intensive Care, 3, 64-65.

22. Vladyka, A. S., Levitsky, E. R., Poddubnaya, L. P., & Gabrielyan, N. I. (1987). Middle molecules and The problem of endogenous intoxication in critical conditions of various etiologies. Anesthesiology and Reanimatology, 2, 37-42.

23. Chuyev, P. N., Ivanchenko, S. A., & Vladyka, A. S. (1999). Ozone hemotherapy and endogenous intoxication in gestoses. Vrachebnoye Delo, 2, 107-108.

24. Belyakov, N. A. (Ed.). (1991). Enterosorption. Leningrad: Sorption Technologies Center.

25. Szymański, I. O. (1996). Therapeutic Hemapheresis Dysfunction. In J. M. Rippe, R. S. Irwin, M. P. Fink, & F. B. Cerra (Eds.), Intensive Care Medicine (Vol. I, pp. 225-231). Boston; New York; Toronto; London: Little, Brown & Co.