Septic shock after dental treatment. Septic shock - causes and pathogenesis

Causes of septic shock:

The reasons for this are:
1. The increasing use of invasive devices for intensive care, that is, intravascular catheters, etc.
2. The widespread use of cytotoxic and immunosuppressive agents (in malignant diseases and transplantations), which cause acquired immunodeficiency.
3.
An increase in the life expectancy of patients with diabetes mellitus and malignant tumors, who have a high level of susceptibility to sepsis.

Sepsis remains the most common cause of death in intensive care units and one of the most fatal pathological conditions. For example, in the United States, about 100,000 people die from sepsis every year.

Sepsis, systemic inflammatory response and septic shock are the consequences of an overreaction to stimulation by bacterial antigens of cells that carry out innate immune responses. An overreaction of cells of innate immunity systems and a secondary reaction of T-lymphocytes and B-cells to it cause hypercytokinemia. Hypercytokinemia is a pathological increase in the blood levels of agents of autoparacrine regulation of cells that carry out innate immune responses and acquired immune responses.

With hypercytokinemia in the blood serum, the content of primary pro-inflammatory cytokines, tumor necrosis factor-alpha and interleukin-1 increases abnormally. As a result of hypercytokinemia and systemic transformation of neutrophils, endothelial cells, mononuclear phagocytes and mast cells into cellular effectors of inflammation in many organs and tissues, an inflammatory process devoid of protective significance occurs. Inflammation is accompanied by alteration of the structural and functional elements of the effector organs. Critical deficiency of effectors causes multiple systemic failure.

Symptoms and signs of septic shock:

Body temperature is higher than 38 degrees Celsius, or below 36 degrees.
Respiratory rate is higher than 20 min-1. Respiratory alkalosis with arterial carbon dioxide tension below 32 mm Hg. Art.
Tachycardia with a heart rate greater than 90 min-1.
Neutrophilia with an increase in the content of polymorphonuclear leukocytes in the blood to a level above 12-10 9 / l, or neutropenia with a content of neutrophils in the blood at a level below 4-10 9 / l.
A shift in the leukocyte formula, in which stab neutrophils account for more than 10% of the total number of polymorphonuclear leukocytes circulating in the blood.

Sepsis is evidenced by two or more signs of a systemic inflammatory reaction with the presence of pathogenic microorganisms in the internal environment confirmed by the data of bacteriological and other studies.

Induction (course) of septic shock

Despite the increase in the minute volume of blood circulation, part of the body cells in septic shock suffer from ischemia caused by disorders of the peripheral circulation. Disorders of peripheral circulation in sepsis and septic shock are the consequences of systemic activation of endothelial cells, polymorphonuclear neutrophils and mononuclear phagocytes. In the activated state, these cells carry out adhesion and exocytosis, which destroys the walls of microvessels. Ischemia in sepsis is partly due to spasm of resistive vessels and precapillary sphincters, which is associated with a deficiency in the activity of constitutional nitric oxide synthetase of endothelial cells and other cells.

The reaction of the systemic circulation to the occurrence of an inflammatory focus of a certain prevalence is aimed at the destruction and elimination of sources of foreign antigens, including their necrobiotically altered tissues. At the same time, the increase in the minute volume of blood circulation (MCV) is partly a consequence of the release into the blood and the suprasegmental action of primary pro-inflammatory cytokines (tumor necrosis factor-alpha, etc.), which increases the MCV. The growth of IOC increases the delivery of leukocytes to the inflammation focus. In addition to the growth of IOC, the systemic inflammatory response and sepsis are characterized by a decrease in total peripheral vascular resistance through dilatation of resistance vessels in the periphery.

This increases the delivery of leukocytes to the capillaries. If, under physiological conditions, neutrophils easily bypass arterioles, capillaries and venules, then with hypercytokinemia they are retained by venule endotheliocytes. The fact is that hypercytokinemia, increasing the expression of adhesive molecules on the surface of both endothelial cells and neutrophils, causes adhesion of polymorphonuclear cells to type II endothelial cells lining the venule wall. Adhesion is the initial stage of pathogenic inflammation, which has no protective value.

Prior to stable adhesion through the simultaneous expression and connection with each other of adhesive molecules of endothelial cells and polymorphonuclear leukocytes, neutrophils roll (rolling) along the endothelial surface. Rolling and adhesion are necessary steps in the transformation of neutrophils into cells that carry out inflammation and are capable of exophagocytosis. These are the stages of inflammation, after the implementation of which the sequence of causes and effects that make up this protective-pathogenic reaction unfolds almost completely.

Inflammation of this genesis has a purely pathological nature, occurs in all organs and tissues, damaging the elements of the executive apparatus. A critical drop in the number of structural and functional elements of most effector organs is the main link in the pathogenesis of the so-called multiple systemic insufficiency. Adhesion leads to obstruction of the venules, which increases the hydrostatic pressure in the capillaries and the mass of the ultrafiltrate entering the interstitium.

According to traditional and correct concepts, sepsis and a systemic inflammatory response are caused by the pathogenic effect of gram-negative microorganisms.

In the induction of a systemic pathological reaction to invasion into the internal environment and blood of gram-negative microorganisms, the following plays a decisive role:

Endotoxin (lipid A, lipopolysaccharide, LPS). This thermostable lipopolysaccharide forms the outer coating of gram-negative bacteria. Endotoxin, acting on neutrophils, causes the release of endogenous pyrogens by polymorphonuclear leukocytes.
LPS-binding protein (LPSP), traces of which are determined in plasma under physiological conditions. This protein forms a molecular complex with endotoxin that circulates with the blood.
Receptor of the cell surface of mononuclear phagocytes and endothelial cells. Its specific element is a molecular complex consisting of LPS and LPSSB (LPS-LPSPS). The receptor is composed of the TL receptor and the surface marker of leukocytes CD 14.

Currently, the incidence of sepsis due to invasion of the internal environment of gram-positive bacteria is increasing. The induction of sepsis by gram-positive bacteria is usually not associated with their release of endotoxin. It is known that peptidoglycan precursors and other components of the walls of gram-positive bacteria cause the release of tumor necrosis factor-alpha and interleukin-1 by cells of the immune systems. Peptidoglycan and other components of the walls of gram-positive bacteria activate the complement system in an alternative way. The activation of the complement system at the level of the whole body causes systemic pathogenic inflammation and contributes to endotoxicosis in sepsis and systemic inflammatory response.

Most experienced clinicians recognize septic shock (SS) with ease. If the same medical researchers are asked to give a definition of this pathological condition, then many different definitions will be given, in many respects contradicting each other. The fact is that the pathogenesis of septic shock remains largely unclear. Despite numerous studies of the pathogenesis of septic shock, antibiotics remain agents whose action is the main etiopathogenetic element of therapy in septic shock.

At the same time, mortality among patients in septic shock is 40-60%. Research aimed at attenuating the action of some of the septic shock mediators has not led to the development of effective therapies. At present, it remains unclear whether the therapy system should be focused on blocking the action of any one of the leading links in the pathogenesis of septic shock, or whether the treatment should be strictly individualized for each of the patients.

Septic shock is a set of disorders of functional systems, in which arterial hypotension and insufficient volumetric blood flow rate at the periphery do not undergo reverse development under the influence of intravenous infusions of certain plasma-substituting agents. This is the result of the unrestricted systemic regulation of the action of some of the mechanisms of innate immune responses. Innate immune responses have their own bactericidal effects and also prepare and induce acquired cellular and humoral immune responses.

The reactions of innate immunity are largely caused by the interaction of ligands of pathogens with humoral and cellular receptors of the body. One of these receptors is TL-receptors (English toll-like, with the properties of a barrier, "alarm", "forward guard"). Currently, more than ten varieties of mammalian TL receptors are known. The combination of a ligand of bacterial origin with a TL receptor triggers a complex of cellular reactions. As a result of these reactions, a bactericidal effect is exerted, inflammation is induced and preparation for a specific immune response occurs. With the redundancy of the complex reaction of the innate immunity systems, septic shock occurs.

There are several levels at which it seems possible to block the pathological response of the innate immune systems, which causes septic shock. The first of them is the level of interaction of exogenous bacterial ligands with humoral and cellular receptors of the innate immunity systems. Previously, it was believed that septic shock is always caused by endotoxin (a lipopolysaccharide of bacterial origin), which is released by gram-negative bacteria. It is now generally accepted that less than 50% of septic shock is caused by gram-positive pathogens.

Gram-positive pathogens release components of their wall, similar in structure to endotoxin. These components are capable of causing septic shock by interacting with cell receptors (receptors on the outer surface of mononuclear phagocytes). It should be noted that when examining a patient, it is very difficult to determine the mechanism of induction of septic shock.

The onset of septic shock is a necessary condition for hypercytokinemia, that is, an increase in the concentration of primary pro-inflammatory cytokines in the circulating blood. In this regard, various methods have been proposed for blocking the action of primary pro-inflammatory cytokines (monoclonal antibodies to tumor necrosis factor-alpha, etc.), which did not reduce mortality in septic shock. The fact is that the effect was exerted on only one element of the immunopathological reaction. To select one anti-inflammatory cytokine as the target of therapy means to influence only one of the many simultaneous and identical links in the pathogenesis of septic shock.

So, we can assume that a number of evolutionarily ancient ligands belonging to gram-negative and gram-positive bacteria, as well as mycobacteria and fungal pathogens, are currently known. These exogenous ligands are capable of interacting with a small number of humoral and cellular receptors, causing sepsis and septic shock. In this regard, it cannot be ruled out that in the future, the pathological reaction of the innate immune systems can be optimally blocked by acting on the humoral and cellular receptors of the ligand of bacteria responsible for the occurrence of septic shock.

To recognize their ligands, TL receptors require auxiliary molecules. Obviously, it remains to be identified that humoral receptor (plasma protein), which binds to the elements of the outer membrane of gram-positive bacteria.

Before the molecular complex of the bacterial wall component and the humoral receptor binds to the TL receptor, it binds to CD 14. As a result, the TL receptor is activated, that is, the signal is transmitted to the cell genes about the start of expression of primary proinflammatory cytokines and bactericidal agents. It is in principle possible to prevent the induction of septic shock by acting on CD14. In addition, it seems theoretically possible to block the pathogenesis of septic shock in the embryo by blocking TL receptors, as well as the transmission of the signal they generate at the postreceptor intracellular level.

Etiology and pathogenesis:

Bacterial infection is the most common cause of septic shock. In sepsis, primary foci of infection are often localized in the lungs, abdominal organs, peritoneum, and also in the urinary tract. Bacteremia is detected in 40-60% of patients in a state of septic shock. In 10-30% of patients in a state of septic shock, it is impossible to isolate a culture of bacteria, the action of which causes septic shock. It can be assumed that septic shock without bacteremia is the result of a pathological immune response in response to stimulation with antigens of bacterial origin. Apparently, this reaction persists after the elimination of pathogenic bacteria from the body by the action of antibiotics and other elements of therapy, that is, its endogenization occurs.

The endogenization of sepsis can be based on numerous, reinforcing each other and realized through the release and action of cytokines, interactions of cells and molecules of innate immunity systems and, accordingly, immune-competent cells. Previously, severe sepsis and septic shock were associated exclusively with gram-negative aerobic bacilli. Currently, the frequency of gram-positive infection as a cause of sepsis is equal to the frequency of sepsis caused by invasion of the internal environment by gram-negative microorganisms. This was due to the widespread use of intravascular catheters, other devices, one way or another located in the internal environment, as well as due to an increase in the frequency of pneumonia. Fungal, viral, and protozoal infections can also cause septic shock.

The systemic inflammatory response is induced by the release from the inflammation focus of the pathogenic bacteria themselves, their toxins, as well as cytokines with the properties of inflammatory mediators. The endotoxin of gram-negative aerobic bacilli has been studied to the greatest extent as an inducer of the systemic inflammatory response. In addition, other bacterial products (toxins) are known that can cause massive release of inflammatory mediators by cells of innate immune systems. Such bacterial products include formyl peptides, exotoxins, enterotoxins, hemolysins-proteoglycans, and lipoteichoic acid, which is formed by gram-positive microorganisms.

Bacterial toxins stimulate the release of cytokines by mononuclear phagocytes with the properties of inflammatory mediators, which first induce and then enhance the systemic inflammatory response. Toxins bind to their cellular receptors, activating regulatory proteins. In particular, this way the transcription factor NF-kB is activated. When activated, NF-kB enhances the expression of cytokine genes with properties of inflammatory mediators.

Activation of NF-kB primarily increases the production of tumor necrosis factor-alpha and interleukin-1 by mononuclear phagocytes. These cytokines are called primary proinflammatory. Tumor necrosis factor-alpha and interleukin-1 stimulate the release by mononuclear phagocytes, as well as immunocompetent cells of interleukins 6 and 8 and other mediators of the inflammatory response: thromboxanes, leukotrienes, platelet activating factor, prostaglandins and activated fractions of the complement system.

It is believed that nitric oxide serves as the main mediator of systemic vasodilation, a drop in total peripheral vascular resistance, and arterial hypotension in patients with septic shock. The inducible (inducible) form of nitric oxide synthetase is expressed and released by endothelial and other cells only under certain conditions. One of these conditions is the effect of primary proinflammatory cytokines on endothelial cells. By causing the expression of an inducible form of synthetase in endothelial, smooth muscle cells of the vascular wall and mononuclear phagocytes, primary proinflammatory cytokines increase the release of nitric oxide at the systemic level.

Strengthening the action of nitric oxide at the systemic level reduces the total peripheral vascular resistance and causes arterial hypotension. In this case, nitric oxide serves as a substrate for the formation of peroxynitrite, that is, the product of the reaction of NO with free oxygen radicals, which has a direct cytotoxic effect. This does not exhaust the role of nitric oxide in the pathogenesis of septic shock. It has a negative inotropic effect on the heart and increases the permeability of the microvascular wall. The inhibition of cardiac contractility in septic shock also occurs due to the negative inotropic effect of tumor necrosis factor-alpha.

The action of tumor necrosis factor-alpha causes edema of the mitochondria and damages the mitochondrial chains of respiratory enzymes. As a result, a deficit of free energy occurs in the cell, and cell death occurs due to hypoergosis. It is known that mitochondria are the main source of free oxygen radicals released into the cytosol of the cell. The action of manganese superoxide dismutase inactivates O2-, which is released by a chain of respiratory enzymes.

At the same time, the antioxidant prevents apoptosis, which is caused by tumor necrosis factor-alpha. This makes us consider the mechanism of apoptosis under the influence of tumor necrosis factor-alpha associated with the release of free oxygen radicals by mitochondria. The production of free oxygen radicals by mitochondria is increased by the action of tumor necrosis factor-alpha. In this case, free oxygen radicals released by mitochondria damage the chains of their respiratory enzymes.

A certain activity of the chains of respiratory enzymes in mitochondria is a necessary condition for the apoptotic action of tumor necrosis factor-alpha. It was shown experimentally that suppression of tissue respiration in mitochondria causes cell resistance to the apoptotic effect of tumor necrosis factor-alpha.

It can be assumed that cells with a particularly high mitochondrial content and increased activity of respiratory enzyme chains have a particularly pronounced sensitivity to the action of tumor necrosis factor-alpha, which damages the mitochondrial respiratory enzyme chains and causes cell hypoergosis. These cells are cardiomyocytes. Therefore, the effect of the factor is especially pronounced at the level of the myocardium, the contractility of which decreases with shock. In this case, the systemic damaging effect of tumor necrosis factor-alpha on mitochondria may underlie tissue hypoxia in septic shock.

In response to the action of phlogogens released during septic shock, the expression of adhesive molecules on the surface of endothelial cells and neutrophils increases. In particular, an integrin complex (CD11 / CD18) appears on the surface of neutrophils, which occurs simultaneously with the appearance on the surface of the endothelial cell of intercellular adhesive molecules complementary to the integrin complex. Expression of the integrin complex on the surface of neutrophils is one of the consequences of the activation of these cells.

Disorders of peripheral circulation in septic shock, adhesion of activated polymorphonuclear leukocytes to activated endothelial cells - all this leads to the release of neutrophils into the interstitium and inflammatory alteration of cells and tissues. At the same time, endotoxin, tumor necrosis factor-alpha, and interleukin-1 increase the production and release of tissue coagulation factor by endothelial cells. As a result, the mechanisms of external hemostasis are activated, which causes fibrin deposition and disseminated intravascular coagulation.

In septic shock, an increase in the expression and release of proinflammatory cytokines causes a pathological response to the release of endogenous immunosuppressants into the interstitium and blood. This determines the phase of immunosuppression of septic shock.

Inducers of immunosuppression in septic shock are: 1) cortisol and endogenous catecholamines; 2) interleukins 10 and 4; 3) prostaglandin E2; 4) soluble tumor necrosis factor receptors; 5) endogenous antagonist of interleukin-1 receptor, etc. Soluble factor receptors bind it in blood and intercellular spaces. With immunosuppression, the content of tissue compatibility antigens of the second type on the surface of mononuclear phagocytes decreases. Without such antigens on their surface, mononuclear cells cannot act as antigen-presenting cells. At the same time, the normal reaction of mononuclear cells to the action of inflammatory mediators is inhibited. All this can cause nosocomial infections and death.

Arterial hypotension in septic shock is mainly a consequence of a decrease in total peripheral vascular resistance. Hypercytokinemia and an increase in the concentration of nitric oxide in the blood during septic shock causes the expansion of arterioles. At the same time, through tachycardia, the minute volume of blood circulation increases compensatory. Arterial hypotension in septic shock occurs despite a compensatory increase in the minute volume of blood circulation. The total pulmonary vascular resistance increases during septic shock, which can be partly associated with the adhesion of activated neutrophils to activated endothelial cells of the pulmonary microvessels.

With septic shock, the following signs of juxtacapillary blood shunting are revealed:
1) lactic acidosis;
2) a decrease in arteriovenous oxygen differences, that is, differences in oxygen content between arterial and venous blood.

With septic shock, the capacitive vessels are dilated, which leads to general venous hyperemia. Expansion of arterioles and veins is expressed in septic shock in different ways in different areas. This determines the pathological variability of pre- and postcapillary vascular resistance. Pathological variability causes an abnormal redistribution of the minute volume of blood circulation and the volume of circulating blood. Vascular dilation in septic shock is most pronounced in the focus of inflammation. Expansion of blood vessels in septic shock is associated with an increase in the content of endogenous vasodilators in the blood and a decrease in the sensitivity of alpha-adrenergic receptors of the vascular wall to endogenous catecholamines.

There are the following main links in the pathogenesis of peripheral circulatory disorders in septic shock:
1) an increase in the permeability of the wall of microvessels;
2) an increase in the resistance of microvessels, which is enhanced by cell adhesion in their lumen;
3) low reaction of microvessels to vasodilating influences;
4) arterio-venular shunting;
5) drop in blood flow.

In the experiment, it was shown that the total cross-sectional area of ​​the capillaries in experimental animals in a state of septic shock decreases. This is a consequence of pathogenic intercellular interactions with the participation of endothelial cells. A decrease in the total lumen of capillaries in patients in a state of septic shock is manifested by inhibition of reactive hyperemia. Reactive hyperemia is suppressed by disorders of local regulation of blood flow through microvessels and a drop in the ability of blood cells to pass through capillaries. In particular, this ability reduces the appearance of adhesive molecules on the surface of neutrophils and monocytes. In addition, this ability decreases due to a decrease in the deformability of neutrophils and erythrocytes.

It is known that in septic shock, the activity of the constitutional (constantly inherent in the cellular phenotype) nitric oxide synthetase decreases. The action of constitutional synthetase increases blood flow in the periphery. A drop in the activity of this enzyme reduces blood flow in the periphery, which inhibits reactive hyperemia. In patients in a state of septic shock, endothelial edema, fibrin deposits in microvessels and intercellular spaces, an increase in the adhesive capacity of neutrophils and endothelial cells, as well as the formation of aggregates from neutrophils, platelets and erythrocytes in venules, arterioles and capillaries are detected. In some cases, the opening of arterio-venular anastomoses occurs as a cause of juxtacapillary bypass grafting.

Hypovolemia is one of the factors of arterial hypotension in septic shock. There are the following causes of hypovolemia (drop in heart preload) in patients in a state of septic shock: 1) dilatation of capacitive vessels; 2) loss of the liquid part of the blood plasma in the interstitium due to the pathological growth of capillary permeability. A drop in cardiac preload and total peripheral vascular resistance are not all causes of arterial hypotension in septic shock.

It also causes a negative effect on the heart of septic shock mediators. Both the left and right ventricles of the heart with septic shock successively go through the stages of rigidity (failure of diastolic function) and dilatation (failure of systolic function). Rigidity and dilatation are not associated with a drop in blood flow through the coronary arteries and an increase in the oxygen demand of cardiomyocytes. The pumping function of the heart in septic shock is inhibited by tumor necrosis factor-alpha, as well as interleukin-1. The inhibition of the pumping function of the heart in septic shock is partly associated with pulmonary arterial hypertension and a decrease in the sensitivity of the beta-adrenergic receptors of the heart.

It can be assumed that in most patients in a state of septic shock, the drop in oxygen consumption by the body is mainly due to primary disorders of tissue respiration. In cardiogenic shock, lactate metabolic acidosis is caused by severe circulatory hypoxia. At the same time, the oxygen tension in the mixed venous blood is below 30 mm Hg. Art. In septic shock, mild lactic acidosis develops with normal oxygen tension in mixed venous blood.

Lactic acidosis in septic shock is considered a consequence of a decrease in pyruvate dehydrogenase activity and secondary accumulation of lactate, rather than a drop in blood flow at the periphery. In the case of septic shock, the reasons for the decrease in the capture of free energy by the cell during aerobic biological oxidation are the cytotoxic effects (direct or indirect) of endotoxin, nitric oxide, tumor necrosis factor-alpha. The pathogenesis of septic shock largely consists of biological oxidation disorders and is determined by cell hypoergosis as a consequence of tissue hypoxia, which developed under the influence of endotoxemia.

Disorders of peripheral circulation in sepsis are systemic in nature and develop with arterial normotension, which is supported by an increase in the minute volume of blood circulation. Systemic microcirculation disorders manifest themselves as a decrease in pH in the gastric mucosa and a drop in the oxygen saturation of blood hemoglobin in the hepatic veins. Hypoergosis of intestinal barrier cells, the action of immunosuppressive links in the pathogenesis of septic shock - all this reduces the protective potential of the intestinal wall, which is another cause of endotoxemia in septic shock.

David C. Dale, Robert G. Petersdorf G. Petersdorf)

Definition. Septic shock is characterized by insufficient tissue perfusion due to bacteremia, most often caused by gram-negative intestinal bacteria. Most patients have hypotension, oliguria, tachycardia, tachypnea, and fever. Circulatory insufficiency is caused by diffuse damage to cells and tissues, as well as stagnation of blood in the microvasculature.

Etiology and Epidemiology. Septic shock can be caused by gram-positive microorganisms, mainly staphylococci, pneumococci and streptococci, but more often it develops with bacteremia as a result of infection with gram-negative pathogens. These include Escherichia coli, Klebsiella, other enterobacteriaceae, Proteus, Pseudomonas aeruginosa, and Serratia. An important cause of septic shock is also bacteremia when infected with meningococci or gram-negative anaerobic bacteroids. With bacteremia caused by gram-negative pathogens, shock syndrome is not caused by the penetration of bacteria into the bloodstream as such, it develops under the influence of microbial toxins. The most studied of these toxins is endotoxin, which is a substance of the lipopolysaccharide nature of the bacterial wall.

Gram-negative bacteremia and septic shock develop mainly in inpatients, usually against the background of an underlying disease, in which infectious agents enter the bloodstream. Predisposing factors include diabetes mellitus, cirrhosis of the liver, leukemia, lymphoma or advanced carcinoma, antineoplastic chemotherapeutic agents and immunosuppressants, and a variety of surgical procedures and infections of the urinary, biliary tract, and gastrointestinal tract. Groups of special ka are newborns, pregnant women and elderly people with impaired urination as a result of prostate pathology. The incidence of sepsis in bacteremia with gram-negative microorganisms is increasing, and currently in some large city hospitals it is 12 per 1000 hospitalized patients. Along with these factors, the widespread use of antibiotics, glucocorticoid drugs, intravenous catheters, humidifiers and other hospital equipment, as well as an increase in the life expectancy of patients with chronic diseases, contribute to an increase in the scale of this serious problem (Chapters 84 and 85).

Pathogenesis, pathological human anatomy and physiology. Most of the bacteria that cause gram-negative sepsis are common commensals of the gastrointestinal tract, from which they can spread to adjacent tissues, for example, in peritonitis due to perforation of the appendix, or can migrate from the perineal region to the urethra or bladder. Gram-negative bacteremia usually develops against the background of a local primary infection of the genitourinary and biliary tract, gastrointestinal tract or lungs, and much less often against the background of infection of the skin, bones and joints. Patients with burns and leukemia often have skin or lung infections as entry gates. In many cases, especially in patients with debilitating diseases, cirrhosis and cancer, it is not possible to identify the primary focus of infection. If, with bacteremia, metastatic lesions of distant parts of the body occur, then classic abscesses are formed in them. However, more often the autopsy results for gram-negative sepsis indicate, first of all, a primary focus of infection and damage to target organs, namely: edema, hemorrhage and the formation of hyaline membranes in the lungs, tubular or cortical necrosis of the kidneys, focal myocardial necrosis, superficial ulceration of the gastrointestinal mucosa. tract, blood clots in the capillaries of many organs.

Basic mechanisms of pathophysiology. Septic shock develops as a result of the effect of bacterial products on cell membranes and components of the blood coagulation and complement systems, which leads to increased coagulability, damage to cells and impaired blood flow, especially microcirculation. Experimental data on the administration of bacteria and endotoxin indicate that many of these reactions start simultaneously; Most modern ideas about the pathophysiology of septic shock are based on the results of studying the effect of bacterial endotoxin and its toxic component, lipid A.

Endotoxin and other bacterial products activate phospholipases of the cell membrane, which leads to the release of arachidonic acid and stimulates the synthesis and release of leukotrienes, protaglandins and thromboxanes. In cells containing phospholipase A2 (for example, neutrophils, monocytes, platelets), a platelet activating factor (PAF) is also formed. These inflammatory mediators have a major effect on vasomotor tone, small vessel permeability, and leukocyte and platelet aggregation. For example, thromboxane A 2 and prostaglandin F 2 a cause marked vasoconstriction, leukotrienes C4 and D4 increase the permeability of small vessels, and leukotriene B4 and PAF promote aggregation and activation of neutrophils. Despite the fact that the opposite actions and interactions of these substances are a very complex process, their total effect on the development of shock, apparently, is very significant (Chapter 68 "Prostaglandins and Eicosanoids").

Microorganisms activate the classical complement pathway, and endotoxin activates the alternative pathway; both pathways lead to the formation of C3a and C5a, which affect the aggregation of leukocytes and platelets and vascular tone. Complement activation, the formation of leukotriene, and the direct effects of endotoxin on neutrophils cause the accumulation of these inflammatory cells in the lungs, the release of the enzymes they contain, and the production of toxic acid radicals that damage the pulmonary endothelium and cause acute respiratory failure syndrome. The activation of the coagulation system leads to the formation of thrombin and the formation of blood clots in the microvasculature of many tissues.

Gram-negative bacteria or endotoxin stimulate the release of catecholamines and glucocorticoids from the adrenal glands, histamine from mast cells, and serotonin from platelets. The secretion of opioids in the central nervous system, the formation of bradykinin from kininogen, and the production of vasoactive arachidonate occur simultaneously in many cells. Tachycardia, hypotension and developing circulatory collapse are the result of the combined effects of substances. Their inhibitors and antagonists are used clinically to alter the course of septic shock. It is now recognized that injection of glucocorticosteroids prior to administration of endotoxin to experimental animals provides a protective effect believed to be related to blocking the release of arachidonic acid from cell membranes. If endotoxin is first administered, the effect after glucocorticoid injection is much less pronounced. The secretion of opioids, i.e., b-endorphins and enkephalins, may play a decisive role in the development of shock. Several experiments have shown that naloxone, an opiate antagonist, significantly enhances cardiovascular function.

Septic shock is accompanied by cell damage and death as a result of direct exposure to endotoxin and other products of bacterial origin, indirect exposure to endogenous mediators, and tissue anoxia. The vascular endothelium is especially susceptible to these influences; experimental data indicate diffuse damage, vacuolization and desquamation of these cells. Anoxia and the release of hormones (eg, catecholamines, glucagon, insulin, glucocorticoids) cause a sharp shift in the conditions of tissue metabolism from aerobic to anaerobic changes and fat metabolism, protein catabolism, hypoglycemia, lactic acidosis. Many of the clinical consequences of septic shock are due to these metabolic changes.

Hemodynamic disorders. At an early stage of the development of shock, blood accumulates in the capillary bed, and plasma proteins sweat into the insterstitial fluid. This, in turn, leads to a sharp decrease in the effective volume of circulating blood, a decrease in cardiac output, as well as systemic arterial hypotension. In the future, the activity of the sympathetic nervous system increases, the vessels narrow and the blood flow to the vessels, internal organs and skin is selectively reduced. If insufficient perfusion of vital organs continues, metabolic acidosis and severe damage to the parenchymal organs occur, and the shock becomes irreversible. In humans, the kidneys and lungs are especially sensitive to endotoxin; at the same time, oliguria and tachypnea develop first, and in some cases, pulmonary edema. In general, in the early stages of shock, the heart and brain are damaged to a lesser extent; therefore, heart failure and coma are late and often terminal manifestations of shock syndrome. There is also experimental evidence that after the introduction of live gram-negative bacteria around the capillary bed of sensitive organs there is a significant arteriovenous shunting of the blood. This enhances tissue anoxia. In some cases, damaged cells seem to be unable to use the available oxygen. The overall result of insufficient tissue perfusion is a sharp decrease in arteriovenous (AV) difference in oxygen content and lactic acidemia.

In the early stages of septic shock, vessels usually dilate first and cardiac output increases, systemic vascular resistance decreases and central venous pressure decreases, and stroke volume increases. In contrast, in the later stages, vasoconstriction with an increase in their systemic resistance, a decrease in cardiac output, a decrease in central venous pressure and a decrease in stroke volume predominate. Examination of large groups of patients with septic shock revealed certain types of clinical and laboratory disorders: 1) unchanged cardiac output, blood volume, circulation rate, unchanged or increased central venous pressure, unchanged or increased pH values, decreased peripheral vascular resistance; the skin is warm and dry; despite hypotension, oliguria and lactic acidemia, the prognosis is generally favorable; it is believed that shock in this case is due to shunting of blood through arteriovenous anastomoses, which leads to impaired perfusion of vital organs; 2) low blood volume and central venous pressure, high hematocrit, increased peripheral vascular resistance, low cardiac output, hypotension, oliguria with a moderate increase in blood lactate levels and unchanged or slightly increased pH; it is possible that before the development of bacteremia, these patients had some hypovolemia, and their prognosis is quite favorable, provided that the intravascular blood volume is restored, treated with appropriate antibiotics, eliminated or drained of septic foci and prescribing vasoactive drugs; 3) unchanged blood volume, high central venous pressure, unchanged or high cardiac output, decreased peripheral vascular resistance against a background of pronounced metabolic acidosis, oliguria, and a very high level of lactate in the blood, indicating insufficient tissue perfusion or insufficient oxygen uptake; despite the fact that the hands and feet of these patients are warm and dry, the prognosis in these cases is poor; 4) low blood volume, central venous pressure and cardiac output, pronounced decompensated metabolic acidosis and lactic acidemia; hands and feet of these patients are cold to the touch and cyanotic. The prognosis in these cases is extremely unfavorable.

These data indicate different stages of septic shock: from hyperventilation, respiratory alkalosis, vasodilation, increased or unchanged cardiac output at an early stage, to a decrease in perfusion with pronounced lactic acidemia and metabolic acidosis, low cardiac output, as well as insignificant AV oxygen difference in irreversible late stage of shock. Moreover, in some patients, the correlation between the outcome of shock and hemodynamic disturbances is low.

Complications. Disruption of coagulation processes. In most patients with septic shock, a number of clotting factors are deficient due to their increased consumption. This syndrome is called disseminated intravascular coagulation (DIC). Its pathogenesis consists in the activation of the internal coagulation system by means of factor XII (Hageman factor) with the subsequent deposition of fibrin-glued platelets on capillary thrombi formed as a result of a generalized Schwarzmann reaction. The formation of fibrin-glued platelet masses is typical for DIC, characterized by a decrease in the level of factors II, V and VIII, a decrease in the amount of fibrinogen and platelets. The development of moderate fibrinolysis with the appearance of cleavage products is possible. These clotting disorders occur to varying degrees in most patients with septic shock, but clinically, bleeding is usually absent, despite the fact that hemorrhages sometimes appear due to thrombocytopenia or deficiency of coagulation factors. A more serious consequence of progressive DIC is the formation of capillary blood clots, particularly in the lungs. If there are no signs of bleeding, coagulopathy does not require special treatment, it spontaneously resolves as the shock is treated.

Respiratory failure. Respiratory failure is one of the most important causes of death in patients with shock, especially after correction of hemodynamic disturbances. Significant factors in the development of acute respiratory failure (ARF) are pulmonary edema, hemorrhages, atelectasis, the formation of hyaline membranes and the formation of capillary thrombi. Severe pulmonary edema may result from a marked increase in capillary permeability. It can develop in the absence of heart failure. Respiratory failure can occur and worsen even after other disorders have disappeared. Pulmonary surfactant levels decrease with progressive decrease in respiratory function of the lungs.

Renal failure Oliguria develops in the early stages of shock and is probably due to a decrease in intravascular blood volume and inadequate renal perfusion. If the latter remains insufficient, acute tubular necrosis develops. Sometimes necrosis of the cortical layer occurs, similar to that which occurs in the generalized phenomenon of Schwartzmann.

Heart failure. Many patients with septic shock develop myocardial insufficiency, even if they did not have heart disease prior to the onset of shock. Based on experimental data, it is believed that heart failure develops under the influence of a substance formed as a result of the activity of lysosomal enzymes in the zone of tissue ischemia. This substance is called myocardial depression factor (FDM). Functionally, the pathology manifests itself as left ventricular failure, as evidenced by an increase in pressure in the left ventricle at the end of diastole.

Dysfunctions of other organs. Superficial ulceration of the mucous membrane of the gastrointestinal tract is often determined, which is manifested by bleeding, as well as liver dysfunctions in the form of hypoprothrombinemia, hypoalbuminemia and moderate jaundice.

Clinical manifestations and laboratory data. Bacteremia with gram-negative infection usually begins acutely with chills, fever, nausea, vomiting, diarrhea, and prostration. As the shock develops, tachycardia, tachypnea, hypotension join them, the patient's arms and legs become cold to the touch and pale, often cyanotic, the patient is inhibited, oliguria appears. Shock caused by gram-negative pathogens, with a pronounced clinical picture, is easy to diagnose, but sometimes clinical signs can be erased, especially in the elderly, debilitated patients or in children. Hypotension of unknown origin, increasing confusion and disorientation or hyperventilation may be the only key points in the diagnosis of septic shock. Some patients have hypothermia, and the absence of fever often makes it difficult to recognize the disease. Occasional jaundice is indicative of a biliary tract infection, intravascular hemolysis, or toxic hepatitis. As the shock progresses, oliguria persists, signs of heart and respiratory failure and coma begin to grow. Death usually occurs as a result of pulmonary edema, secondary generalized anoxemia due to respiratory failure, cardiac arrhythmias, DIC with bleeding, cerebral anoxia, or a combination of these factors. ...

Laboratory findings vary dramatically and in many cases depend on the cause of the shock syndrome, as well as on the stage of shock. The hematocrit is often increased and becomes less than normal as the volume of circulating blood is restored. Leukocytosis is usually noted (the number of leukocytes is 15-30 10 9 / l) with a shift in the white blood count to the left. However, the number of leukocytes may be within the normal range, and some patients have leukopenia. Platelet count usually decreases, prothrombin time and partial thromboplastin time may be altered, reflecting consumption of clotting factors.

There are no specific changes in the urine. Initially, its specific gravity is high; if oliguria continues, isostenuria develops. The levels of blood urea nitrogen (BUN) and creatinine are increased and creatinine clearance is decreased.

Simultaneous determination of the osmotic pressure of urine and plasma can be used to recognize threatening renal failure. If the osmotic pressure of urine exceeds 400 mOsmol, and the ratio of osmotic pressure of urine and plasma exceeds 1.5, renal function is preserved and oliguria is probably due to a decrease in circulating blood volume. On the other hand, an osmotic pressure of less than 400 mOsmol and a urine-to-plasma pressure ratio of less than 1.5 indicate renal failure. Along with this, prerenal azotemia can be judged by such indicators as the level of sodium in the urine less than 20 mol / l, the ratio of creatinine in urine and serum more than 40, or the ratio of urea nitrogen in the blood and creatinine in the serum of more than 20. Types of electrolyte disturbances vary significantly, however, there is a tendency towards hyponatremia and hypochloremia. Serum potassium levels can be high, low, or normal. The concentration of bicarbonate is usually low and the level of lactate in the blood rises. A low pH in kguvie and a high level of lactate in it are among the most reliable signs of insufficient tissue perfusion.

At the beginning of endotoxin shock, respiratory alkalosis is determined, manifested by a low pco2 and high arterial blood pH, probably as a result of progressive anoxemia and excretion of carbon dioxide against the background of hyperventilation of the lungs aimed at compensating for lactic acidemia. As the shock progresses, metabolic acidosis develops. Anoxemia is often sharply expressed, with p o2 below 70 mm Hg. Art. The ECG usually shows a decrease in the segment ST, negative wave T and different types of arrhythmias, in connection with which the diagnosis of myocardial infarction may be misdiagnosed.

Before starting treatment, pathogens are found in blood cultures in patients with septic shock, but bacteremia may be unstable. and blood culture results may be negative in some cases. Moreover, the results of bacteriological studies can be distorted, since many patients manage to take antimicrobial drugs by the time of examination. Negative results do not rule out a diagnosis of septic shock. Culture results from the primary site of infection can help establish a diagnosis, but they can be distorted by the influence of previous chemotherapy. The ability of endotoxin to coagulate the blood of the horseshoe crab Limulus is the basis of the endotoxinemia test, but it is not widely available and therefore has limited clinical use.

Diagnosis. With a chill in a patient, fever and identification of an obvious focus of infection, it is not difficult to recognize septic shock. However, none of these signs may be present. In the elderly, and especially in debilitated patients, the infection may not be accompanied by a febrile state. In a patient who has no radiological changes in the lungs, but confused consciousness and is disoriented against the background of hyperventilation, the reason for it is not clear, one should think about septic shock. It is most often confused with diseases such as pulmonary embolism, myocardial infarction, cardiac tamponade, aortic dissection, and silent bleeding.

Flow. Careful observation of the patient is the cornerstone of rational treatment for septic shock. Continuous recording of clinical data is very helpful. At the patient's bedside, it is especially important to monitor four main indicators:

1. The state of pulmonary blood flow (and preferably the function of the left ventricle) is monitored using a Swan-Gantz catheter. The pressure in the pulmonary vessels is higher than 15-18 cm of water. Art. indicates stagnation. If a Swan-Gantz catheter is not available, central venous pressure (CVP) should be measured. The introduction of a catheter into a large vein or into the right atrium provides accurate data on the relationship between the state of the right ventricle and the volume of circulating blood, which makes it possible to regulate the volume of fluid injected. Central venous pressure is higher than 12-14 mm of water. Art. indicates some danger of continued administration of fluids and the threat of developing sudden pulmonary edema. It is very important to ensure that blood flow through the catheter is free and that the catheter is not in the right ventricle. Every patient with septic shock needs to have either a Swann-Gantz catheter inserted or to measure the CVP.

2. Pulse pressure allows you to estimate the value of the stroke volume of the heart.

3. The vasoconstriction is indicative of peripheral vascular resistance, although it does not fully reflect disturbances in blood flow in the kidneys, brain, or intestines.

4. Hourly measurement of the volume of excreted urine allows you to control the level of blood flow in the internal organs and the degree of their perfusion. This usually requires the insertion of an indwelling urinary catheter.

The listed indicators quite fully reflect the condition of patients with septic shock and allow rational treatment. The results of an indirect measurement of blood pressure do not allow to accurately determine the state of hemodynamics, since the perfusion of vital organs may be adequate in patients with hypotension; and vice versa, in some patients in whom blood pressure is within the normal range, blood stagnation and insufficient blood flow in the vessels of the internal organs may develop. Direct blood pressure measurements can be helpful, but this is not necessary in practice. If possible, these patients should be treated in intensive care units in hospitals where laboratories are equipped to measure arterial blood pH, blood gas, lactate content, and renal function and blood electrolyte levels.

Treatment. Maintenance of respiratory function. In many patients with septic shock, the arterial blood horn is markedly reduced. In this regard, it is important for them from the very beginning to ensure free breathing and the supply of oxygen through a nasal catheter, mask or tracheostomy. Ventilation of the lungs is provided already in the early stages of shock in order to prevent the development of acidosis and hypoxia.

Restoration of the volume of circulating blood. Focusing on the indicators of CVP or pressure in the pulmonary vessels, it is necessary to restore the volume of circulating blood by injecting blood (with anemia), plasma or other colloidal solutions. For this purpose, it is preferable to use human serum albumin, as well as the corresponding electrolyte solutions, primarily dextrose in isotonic sodium chloride solution and bicarbonate (the latter has an advantage over lactate in the treatment of a patient with acidosis). In most cases, bicarbonate is administered in order to bring the blood pH to about 7.2-7.3, but not higher. The amount of fluid required for treatment can significantly exceed the normal blood volume and reaches 8-12 liters in just a few hours. Large amounts of fluid may be required even when the cardiac index is within the normal range. With hypotension, oliguria is not a contraindication for the continuation of the intensive administration of fluids. In order to prevent pulmonary edema in cases where CVP reaches approximately 10-12 cm of water. Art., and the pressure in the pulmonary artery is 16-18 cm of water. Art., you should enter furosemide in order to enhance diuresis.

Antibiotic treatment. Blood cultures and appropriate fluids and exudates should be cultured prior to treatment. The drugs should be administered intravenously, with the use of bactericidal antibiotics is desirable. When blood culture and susceptibility testing is obtained, one of the appropriate antibiotics recommended for specific infections should be prescribed, as reviewed in Chap. 88. In the absence of data on the pathogen, the basis of initial therapy should be the principle of choosing a drug with the widest possible spectrum of action and effective in case of infection with the most likely pathogen. Analysis of clinical data can be of great help in the initial selection of antimicrobial agents. For example, if a young woman has dysuria, chills, side abdominal pain, and septic shock, then her bacteremia is likely caused by E. coli. In a patient with burns, the cause of gram-negative sepsis is probably Pseudomonas aeruginosa. During influenza epidemics, drugs should be selected for their effect on Staphylococcus aureus, as it often causes severe bacterial superinfections and pneumonia.

If the etiology of septic shock is not established, treatment with gentamicin (or tobramycin) and cephalosporin or penicillinase-resistant penicillin preparations should be prescribed at the same time; many doctors add carbenicillin to these drugs. In view of the toxic effect on the vestibular part of the VIII pair of cranial nerves, gentamicin, tombramycin and other aminoglycosides should be prescribed with caution to patients with oliguria. If a bacteroid infection is suspected, chloramphenicol (chloramphenicol), 7-chlorlincomycin (clindamycin), or carbenicillin can be added to these drugs. Having received the results of the crops, the necessary amendments are made to the treatment.

Surgical intervention. Many patients with septic shock have abscesses, heart attacks or intestinal necrosis, inflammation of the gallbladder, infection of the uterus, pyonephrosis, or other focal inflammatory processes that require surgical drainage or removal. As a rule, surgical intervention is necessary for the successful treatment of a patient with shock, even in cases when his condition is extremely serious. The operation should not be postponed in order to stabilize his condition, as in these cases it continues to deteriorate until the septic focus is removed or drained.

Vasoactive drugs. Typically, septic shock is accompanied by maximal stimulation of alpha-adrenergic receptors, so pressor agents that act by stimulating them (norepinephrine, levarterinol, and metaraminol) are usually not indicated. In septic shock, two groups of drugs were effective: beta-receptor stimulants (especially isoproterenol and dopamine) and alpha-receptor blockers (phenoxybenzamine and phentolamine).

Dopamine hydrochloride is widely used to treat shock patients. Unlike other vasoactive agents, it increases renal blood flow and glomerular filtration, sodium excretion, and urinary excretion. The effect is observed with the introduction of low doses of the drug (1-2 μg / kg per 1 min). At a dose of 2-10 μg / (kg min), it stimulates the beta-receptors of the heart muscle with a subsequent increase in cardiac output, but without an increase in heart rate or blood pressure, at a dose of 10-20 μg / (kg min) slightly stimulates alpha-receptors followed by an increase in blood pressure. At a dose of more than 20 μg / (kg min), stimulation of alpha receptors becomes predominant, while the vasoconstrictor effect can neutralize the dopaminergic effect on the vessels of the kidneys and other internal organs. Treatment should begin with a dose of 2-5 mcg / (kg min) with a further increase until urine flow increases and blood pressure normalizes. In most patients, a dose of 20 mcg / (kg min) or less is effective. Adverse reactions include ectopic rhythm disturbances, nausea and vomiting, and sometimes tachycardia. They usually disappear with a decrease in the dose of the drug.

Isoproterenol counteracts spasm of arterial and venous vessels in the microvasculature by direct vasodilatory action. Along with this, it has a direct inotropic effect on the heart. Cardiac output is increased by stimulating the myocardium and reducing the load on the heart as a result of decreasing peripheral vascular resistance. On average, for an adult, the dose of isoproterenol is 2-8 μg / min. With its introduction, ventricular arrhythmias may occur, and in cases where the introduction of fluid does not correspond to the degree of reduction of vasospasm, the signs of shock may increase.

Phenoxybenzamine, an adrenolytic agent, affects central venous pressure by decreasing vascular resistance and increasing blood flow efficiency. Thus, it causes blood redistribution. Its outflow from the lungs increases, pulmonary edema decreases and gas exchange increases, CVP and residual diastolic pressure in the left ventricle decrease, cardiac output increases, and the narrowing of peripheral venous vessels decreases. The drug is recommended to be administered intravenously at a dose of 0.2-2 mg / kg. Small doses can be administered in a stream, and large doses within 40-60 minutes. At the same time, fluids should be injected in order to compensate for the increase in the permeability of the venous vessels, otherwise shock phenomena will increase. Phenoxybenzamine (not FDA cleared at the time of publication for this purpose) is not available for practical use, and experience with phentolamine is insufficient to be recommended for widespread clinical use.

Treatment with diuretics and cardiac glycosides. It is very important to maintain urinary flow in order to prevent renal tubular necrosis. When the volume of circulating blood is restored, a diuretic should be prescribed, preferably furosemide, so that the amount of urine excreted hourly exceeds 30-40 ml / h. In patients who, despite increased CVP or pressure in the lung vessels, remain hypotensive, digoxin can help, but it should be administered with caution, due to frequent changes in acid-base balance, hyperkalemia and renal dysfunction in septic shock.

Glucocorticoids. Numerous experimental data support corticosteroid drugs for manifestations of endotoxinemia and septic shock. Steroids, apparently, protect cell membranes from damage caused by endotoxins, prevent the transformation of arachidonic acid into its vasoactive derivatives, reduce platelet aggregation and release of enzymes from leukocytes into the extracellular space. Several studies have shown that steroids may also directly reduce peripheral vascular resistance. Due to the complexity of the clinical picture in patients with endotoxic shock, it is rather difficult to prove the unconditional efficacy of steroid drugs. Some controlled studies have shown the effectiveness of methylprednisolone (30 mg / kg) or dexamethasone (3 mg / kg) if the drug was prescribed at the first sign of shock. In an extremely serious condition of the patient, the drug was re-administered at the same dose after 4 hours. The results of these studies and the experience of specialists from many centers indicate in favor of the early prescription of large doses of steroids for a relatively short period (24-48 hours). In the later stages of septic shock, steroids are probably ineffective. Long-term treatment with them is associated with serious problems, such as hyperglycemia, gastrointestinal bleeding, etc., in connection with which their use should be avoided.

Other treatments. In case of bleeding, depending on the cause of the coagulation disorders, whole blood, fresh frozen plasma, cryoprecipitate or platelet mass should be transfused. At the stage of experimental study are naloxone, inhibitors of prostaglandin synthesis, as well as prostacyclin. The use of heparin for disseminated intravascular coagulation remains controversial and forged. Treatment of patients with bacteremia due to gram-negative pathogens using hyperbaric oxygenation did not give any definite results.

Prognosis and prevention of the disease. The use of the listed methods of treatment ensures at least temporarily the survival of most patients. Its effectiveness is evidenced by: .1) correction of brain functions and improvement of the general condition; 2) a decrease in the severity of peripheral cyanosis; 3) warming of the skin of the hands and feet; 4) urine volume 40-50 ml / h; 5) increased pulse pressure; 6) normalization of CVP and pressure in the pulmonary artery; 7) increase in blood pressure.

However, the final outcome depends on a number of other factors. First, from the ability to eliminate the source of infection with surgery or with antibiotics. The prognosis for urinary tract infection, septic abortion, abdominal abscesses, gastrointestinal or biliary fistulas, and subcutaneous or anorectal abscesses is more favorable than with localization of primary foci in the skin or lungs. However, with extensive operations on the organs of the abdominal cavity, carried out on the vital. testimony, he is always very serious. Second, the outcome depends on past contact with the pathogen. In patients with chronic urinary tract infection, bacteremia is rarely complicated by shock caused by gram-negative pathogens, possibly due to the fact that they develop tolerance to bacterial endotoxin. Third, the underlying disease matters. If a patient with lymphoma or leukemia develops septic shock during an unresponsive exacerbation of hematologic disease, they rarely survive; conversely, once hematologic remission is achieved, there is a greater likelihood of successful shock treatment. In patients with previous heart disease and diabetes mellitus, the prognosis for septic shock is also rather poor. Fourth, metabolic status is important. Severe metabolic acidosis and lactic acidemia, regardless of the state of cardiac activity, are associated with an unsatisfactory prognosis. Fifth, pulmonary insufficiency, despite the normalization of hemodynamic parameters, is also fraught with an unfavorable prognosis.

The overall mortality rate in septic shock remains at the level of 50%, however, as the monitoring of the patient's condition improves and his treatment is more physiologically justified, the prognosis will become more favorable.

The unsatisfactory results of treatment in septic shock are not due to the lack of effective antibiotics or vasoactive drugs. Obviously, the main obstacle to successful treatment is the delay in the initiation of appropriate treatment. Septic shock is usually recognized too late and too often after irreversible changes have taken place. Since 70% of patients who are likely to develop septic shock are in hospitals before they show signs of shock, it is very important to carefully monitor their condition, conduct vigorous and early treatment for infections, and perform appropriate surgical operations before catastrophic complications develop. ... It is especially important to avoid contamination of venous and urinary catheters, which can become gateways for gram-negative pathogens that cause sepsis, and to remove these catheters from all patients as soon as possible at the earliest opportunity. There is preliminary evidence that early treatment for septic shock contributes to a better prognosis. And finally, the protective effect of antisera in experimental animals may be used in the treatment of humans.