What is septic shock. Sepsis and Septic Shock - Causes, Symptoms, Treatment Renal Replacement Therapy

Sepsis, being a primary medical problem today, continues to be one of the leading causes of death, despite various discoveries in the pathogenesis of this disease and the application of new principles of treatment. Septic shock is a serious complication of sepsis.

Septic shock is a complex pathophysiological process resulting from the action of an extreme factor associated with the breakthrough of pathogens or their toxins into the bloodstream, which, along with damage to tissues and organs, causes excessive inadequate tension of nonspecific adaptation mechanisms and is accompanied by hypoxia, tissue hypoperfusion, and profound metabolic disorders.

Some of the known mediators of endothelial damage involved in septic reactions are:

• tumor necrotizing factor (TNF);
• interleukins (IL-1, IL-4, IL-6, IL-8);
• platelet activating factor (PAF);
• leukotrienes (B4, C4, D4, E4);
• thromboxane A2;
• prostaglandins (E2, E12);
• prostacyclin;
• gamma interferon.

Along with the aforementioned mediators of endothelial damage, many other endogenous and exogenous mediators are involved in the pathogenesis of sepsis and septic shock, which become components of the inflammatory response.

Potential mediators of the septic inflammatory response:

• endotoxin;
• exotoxin, part of the cell wall of a gram-negative bacterium;
• complement, metabolic products of arachidonic acid;
• polymorphonuclear leukocytes, monocytes, macrophages, platelets;
• histamine, cell adhesion molecules;
• coagulation cascade, fibrinolytic system;
• toxic oxygen metabolites and other free radicals;
• kallikrein-kinin system, catecholamines, stress hormones.

In the pathogenesis of septic shock, the most important link is microcirculation disorders. They are caused not only by vasoconstriction, but also by a significant deterioration in the aggregate state of blood with a violation of its rheological properties and the development of disseminated intravascular coagulation (DIC) syndrome or thrombohemorrhagic syndrome. Septic shock leads to disorders of all metabolic systems. Disrupted carbohydrate, protein and fat metabolism, the utilization of normal energy sources - glucose and fatty acids is sharply suppressed. In this case, there is a pronounced catabolism of muscle protein. In general, the metabolism is shifted to the anaerobic pathway.

Thus, the pathogenesis of septic shock is based on deep and progressive disorders of humoral regulation, metabolism, hemodynamics and oxygen transport. The interrelation of these disorders can lead to the formation of a vicious circle with a complete depletion of the body's adaptive capabilities. Prevention of the development of this vicious circle is the main task of intensive care of patients with septic shock.

Clinical picture septic shock

Changes in the functions of vital organs under the influence of damaging factors of septic shock form a dynamic pathological process, the clinical signs of which are revealed in the form of dysfunctions of the central nervous system, pulmonary gas exchange, peripheral and central circulation, and subsequently in the form of organ damage.

The breakthrough of the infectious agent from the focus of inflammation or the entry of endotoxin into the bloodstream trigger the primary mechanism of septic shock, in which the pyrogenic effect of the infectious agent and, first of all, endotoxin is manifested. Hyperthermia above 38-39 ° C, shaking chills are key signs in the diagnosis of septic shock. Very often, gradually progressive fever of the hectic or irregular type, reaching extreme values \u200b\u200band uncharacteristic for a given age (40-41 ° C in elderly patients), as well as polypnoea and moderate circulatory disorders, mainly tachycardia (heart rate more than 90 per minute), are considered a reaction for injury and surgery. Sometimes these symptoms are the basis for the diagnosis of a local infection. However, this phase of septic shock is called "warm normotension" and is often not diagnosed. In the study of central hemodynamics, a hyperdynamic circulatory regime is determined (SI more than 5 l / min / m 2) without disturbing oxygen transport (RTK 800 ml / min / m 2 or more), which is characteristic of the early stage of septic shock.

With the progression of the process, this clinical phase of septic shock is replaced by the phase of "warm hypotension", which is characterized by a maximum increase in body temperature, chills, changes in the patient's mental state (agitation, anxiety, inadequate behavior, sometimes psychosis). On examination of the patient, the skin is warm, dry, flushed or pink. Respiratory disorders are expressed as hyperventilation, which further leads to respiratory alkalosis and fatigue of the respiratory muscles. Tachycardia up to 120 beats or more per minute is noted, which is combined with good filling of the pulse and hypotension (Adsyst< 100 мм рт.ст.). Гипотензия скорее умеренная и обыч­но не привлекает внимание врачей. Уже в этой стадии септического шока выявляются признаки неспособности системы кровообращения обеспе­чить потребность тканей в кислороде и питательных веществах, а также создать возможность детоксикации и удаления токсичных метаболитов. Для того чтобы поддержать адекватность перфузии тканей и избежать анаэробного окисления, больным необходим более высокий уровень DO 2 (15 мл/мин/кг вместо 8-10 мл/мин/кг в норме). Однако в этой стадии септического шока даже повышенный СВ (СИ 4,3-4,6 л/мин/м 2) не обес­печивает должной потребности в кислороде.

Often, hemodynamic and respiratory changes are combined with distinct disturbances in the activity of the digestive tract: dyspeptic disorders, pain (especially in the upper abdomen), diarrhea, which can be explained by the peculiarities of serotonin metabolism, initial changes in blood flow in the celiac vessels and activation of the central mechanisms of nausea and vomiting. In this phase of septic shock, there is a decrease in urine output, sometimes reaching the level of oliguria (urination less than 25 ml / h).

The clinical picture of the late stage of septic shock is characterized by impaired consciousness, severe disorders of pulmonary gas exchange, peripheral and central circulatory failure, organ pathology with signs of hepatic and renal failure. The external manifestations of this stage of septic shock are called "cold hypotension". When examining the patient, attention is drawn to the darkening of consciousness, up to the development of a coma; pallor of the skin; acrocyanosis, sometimes significant; oligoanuria. Severe tachypnea (more than 40 breaths in 1 min) is combined with a feeling of lack of air, which does not decrease even with oxygen therapy; inhalation, as a rule, involves accessory muscles.

Chills and hyperthermia are replaced by a decrease in body temperature, often with its critical drop to subnormal numbers. The skin temperature of the distal extremities, even to the touch, is significantly lower than usual. A decrease in body temperature is combined with a distinct autonomic reaction in the form of torrential sweats. Cold, pale cyanotic, wet hands and feet are one of the pathognomonic symptoms of an unfavorable course of generalized infection. At the same time, there are relative signs of a decrease in venous return in the form of desolation of the peripheral venous subcutaneous network. Frequent, 130-160 per minute, weak filling, sometimes arrhythmic, the pulse is combined with a critical decrease in systemic blood pressure, often with a low pulse amplitude.

The earliest and clearest sign of organ damage is progressive renal dysfunction with severe symptoms such as azotemia and increasing oligoanuria (urine output less than 10 ml / h).

Lesions of the gastrointestinal tract are manifested in the form of dynamic intestinal obstruction and gastrointestinal bleeding, which in the clinical picture of septic shock may prevail even in cases when it is not of peritoneal origin. Liver damage is characterized by the appearance of jaundice and hyperbilirubinemia.

It is generally accepted that the supply of oxygen to the body is quite adequate at a hemoglobin concentration\u003e 100 g / l, SаO 2\u003e 90% and SI\u003e 2.2 l / min / m 2. Nevertheless, in patients with a pronounced redistribution of peripheral blood flow and peripheral shunting, oxygen supply even with these indicators may be inadequate, as a result of which hypoxia develops with a high oxygen debt, which is characteristic of the hypodynamic stage of septic shock. High tissue oxygen consumption in combination with low transport of the latter indicates the possibility of an unfavorable outcome, while increased oxygen consumption in combination with an increase in its transport is a sign favorable for almost all types of shock.

Most clinicians believe that peripheral blood changes and metabolic disorders are the main objective diagnostic criteria for sepsis.

The most characteristic changes in the blood: leukocytosis (12 x 10 9 / l) with a neutrophilic shift, a sharp "rejuvenation" of the leukocyte formula and toxic granularity of leukocytes. At the same time, it should be remembered about the non-specificity of violations of certain parameters of peripheral blood, their dependence on circulatory homeostasis, the constantly changing clinical picture of the disease and the influence of therapeutic factors. It is generally accepted that leukocytosis with an increase in the leukocyte index of intoxication (LII\u003e 10) and thrombocytopenia can be characteristic objective criteria for septic shock. Sometimes the dynamics of the leukocyte reaction has a wavy character: the initial leukocytosis is replaced by leukopenia, which coincides in time with mental and dyspeptic disorders, the appearance of polypnoea, and then a rapid increase in leukocytosis is observed again. But even in these cases, the LII value is progressively increasing. This indicator is calculated by the formula [Kalf-Caliph Ya.Ya., 1943]:

where C - segmented neutrophils, P - stab, Yu - young, Mi - myelocytes, P - plasma cells, Mo - monocytes. Li - lymphocytes, E-eosinophils.

The normal value of the index fluctuates around 1. An increase in LII to 4-9 indicates a significant bacterial component of endogenous intoxication, while a moderate increase in the index to 2-3 indicates a limitation of the infectious process or predominant tissue decay. Leukopenia with high LII is always an alarming symptom of septic shock.

In the late stage of septic shock, hematological studies, as a rule, reveal moderate anemia (Нb 90-100 g / l), hyperleukocytosis up to 40 × 10 9 / l and above with a limiting increase in LII up to 20 or more. Sometimes the number of eosinophils increases, which reduces LII, despite a distinct shift in the leukocyte count towards immature forms of neutrophils. Leukopenia with no neutrophilic shift may be observed. When assessing the leukocyte reaction, it is necessary to pay attention to the decrease in the absolute concentration of lymphocytes, which can be 10 times or more below the normal value.

Among the data of standard laboratory control, the indicators characterizing the state of metabolic homeostasis deserve attention. The most common diagnostics of metabolic disorders is based on the monitoring of CBS shifts, blood gases and an assessment of the concentration of lactate in the blood. As a rule, the nature and form of CBS disorders, as well as the level of lactate, depend on the severity and stage of development of the shock. The correlation between the concentrations of lactate and endotoxin in the blood is quite pronounced, especially in septic shock.

In the study of CBS blood in the early stages of septic shock, compensated or subcompensated metabolic acidosis is often determined against the background of hypocapnia and a high level of lactate, the concentration of which reaches 1.5-2 mmol / l or more. In the early stage of septicemia, temporary respiratory alkalosis is most characteristic. Some patients have metabolic alkalosis. In the later stages of the development of septic shock, metabolic acidosis becomes uncompensated and, due to a deficiency of bases, often exceeds 10 mmol / L. The level of lactate acidemia reaches 3-4 mmol / l or more and is a criterion for the reversibility of septic shock. As a rule, a significant decrease in PaO 2, SaO 2 is determined and, consequently, a decrease in the oxygen capacity of the blood. It should be emphasized that the severity of acidosis is highly correlated with prognosis.

In the diagnosis and treatment of septic shock, it becomes more and more necessary to dynamically determine the indicators of central hemodynamics (MOS, VO, SI, OPSS, etc.) and oxygen transport (aV - the difference in oxygen, CaO 2, PaO 2, SaO 2), which allow to assess and determine the stage of shock and compensatory reserves of the body. SI in combination with other factors characterizing the features of oxygen transport in the body and tissue metabolism serve as criteria not only for the effectiveness of oxygen supply, but also for orientation in the prognosis of septic shock and the choice of the main direction of intensive therapy for circulatory disorders with outwardly identical manifestations of this pathological process - hypotension and low rate of diuresis.

In addition to functional research, diagnostics includes the identification of an etiological factor - the identification of the pathogen and the study of its sensitivity to antibacterial drugs. Bacteriological examination of blood, urine, wound exudate, etc. is carried out. With the help of biological tests, the severity of endotoxinemia is investigated. In clinics, diagnostics of immune deficiency is carried out on the basis of general tests: T- and B-lymphocytes, blast transformation, the level of immunoglobulins in the blood serum.

Diagnostic criteria for septic shock:

• the presence of hyperthermia (body temperature\u003e 38-39 ° C) and chills. In elderly patients, paradoxical hypothermia (body temperature<36 °С);
• neuropsychiatric disorders (disorientation, euphoria, agitation, stupor);
• hyper- or hypodynamic syndrome of circulatory disorders. Clinical manifestations: tachycardia (heart rate \u003d 100-120 per minute), adsist< 90 мм рт.ст. или его снижение на 40 мм рт.ст. и более от среднего в отсутствие других причин гипотензии;
• microcirculation disorders (cold, pale, sometimes slightly or intensely icteric skin);
• tachypnea and hypoxemia (heart rate\u003e 20 per minute or PaCO 2<32 мм рт.ст., акроцианоз);
• oligoanuria, urination - less than 30 ml / h (or the need to use diuretics to maintain sufficient diuresis);
• vomiting, diarrhea;
• leukocyte count\u003e 12.0 10 9 / l, 4.0 10 9 / l or immature forms\u003e 10%, LII\u003e 9-10;
• lactate level\u003e 2 mmol / l.

Some clinicians identify a triad of symptoms that serves as a prodrome for septic shock: impaired consciousness (behavior change and disorientation); hyperventilation, determined by eye, and presence of a focus of infection in organism.

In recent years, a point scale for assessing organ failure associated with sepsis and shock (SOFA scale - Sepsis-related Organ Failure Assessment) has been widely used (Table 17.1). It is believed that this scale, adopted by the European Society of Intensive Care, is objective, accessible and easy to assess dysfunction of organs and systems during the progression and development of septic shock.

Table 17.1.

Scale SOFA

Dose of cardiotonics in mg per 1 kg of body weight in 1 min for at least

Dysfunction of each organ (system) is assessed separately, in dynamics, daily, against the background of intensive therapy.

Treatment.

The complexity of the pathogenesis of septic shock determines the multicomponent approach to its intensive therapy, since the treatment of only one organ failure is unrealistic. Only with an integrated approach to treatment can one hope for relative success.

Intensive treatment should be carried out in three principal directions. The first in terms of time and importance - reliable elimination of the main etiological factor or disease that triggered and maintains the pathological process. With an unresolved focus of infection, any modern therapy will be ineffective. Second - treatment of septic shock is impossible without correction of disorders common for most critical conditions: hemodynamics, gas exchange, hemorheological disorders, hemocoagulation, water-electrolyte shifts, metabolic insufficiency, etc. Third - direct impact on the function of the affected organ, up to temporary prosthetics, should be started early, before the development of irreversible changes.

Antibiotic therapy, immunocorrection, and adequate surgical treatment for septic shock are essential in the fight against infection. Early antibiotic treatment should be initiated prior to culture isolation and identification. This is of particular importance in immunocompromised patients, when a delay in treatment for more than 24 hours may result in an unfavorable outcome. In septic shock, immediate parenteral broad-spectrum antibiotics are recommended. The choice of antibiotics is usually determined by the following factors: the likely pathogen and its sensitivity to antibiotics; underlying disease; the patient's immune status and the pharmacokinetics of antibiotics. As a rule, a combination of antibiotics is used, which ensures their high activity against a wide range of microorganisms before the results of microbiological research become known. Combinations of 3-4th generation cephalosporins (longacef, rocephin, etc.) with aminoglycosides (gentamicin or amikacin) are often used. The dose of gentamicin for parenteral administration is 5 mg / kg / day, amikacin - 10-15 mg / kg of body weight. Longacef has a long half-life, so it can be used once a day up to 4 g, rocephin - up to 2 g once a day. Antibiotics, which have a short half-life, must be given in high daily doses. Claforan (150-200 mg / kg / day), ceftazidime (up to 6 g / day) and cephalosporin (160 mg / kg / day) are widely used. When treating patients with a septic focus within the abdominal cavity or small pelvis, you can resort to a combination of gentamicin and ampicillin (50 mg / kg per day) or lincomycin. If a gram-positive infection is suspected, vancomycin (vancocin) is often used up to 2 g / day. When determining the sensitivity to antibiotics, therapy can be changed. In cases where it was possible to identify the microflora, the choice of antimicrobial drug becomes direct. It is possible to use monotherapy with antibiotics with a narrow spectrum of action.

In some cases, along with antibiotics, powerful antiseptics can be included in the antibacterial combination of drugs: dioxidine up to 0.7 g / day, metronidazole (flagil) up to 1.5 g / day, solafur (furagin) up to 0.3-0.5 g / day Such combinations are preferably used in cases where it is difficult to expect sufficient efficacy from conventional antibiotics, for example, with previous long-term antibiotic therapy.

An important link in the treatment of septic shock is the use of agents that enhance the body's immune properties. Patients are injected with gamma globulin or polyglobulin, specific antitoxic sera (antistaphylococcal, antipseudomonal).

Powerful intensive care will not be successful if the infection is not removed surgically. Urgent surgery can be essential at any stage. Drainage and removal of the focus of inflammation are required. Surgical intervention should be low-traumatic, simple and sufficiently reliable to ensure the primary and subsequent removal of microorganisms, toxins and tissue decay products from the focus. It is necessary to constantly monitor the appearance of new metastatic foci and eliminate them.

In the interests of optimal homeostasis correction, the clinician must simultaneously correct various pathological changes. It is believed that for an adequate level of oxygen consumption, it is necessary to maintain a SI of at least 4.5 l / min / m 2, while the DO 2 level should be more than 550 ml / min / m 2. Tissue perfusion pressure can be considered restored if the mean blood pressure is not less than 80 mm Hg, and OPSS is about 1200 dyn s / (cm 5 m 2). At the same time, excessive vasoconstriction must be avoided, which inevitably leads to a decrease in tissue perfusion.

Carrying out a therapy that corrects hypotension and maintains blood circulation is very important in septic shock, since circulatory disturbance is one of the leading symptoms of shock. The first remedy in this situation is to restore adequate vascular volume. At the beginning of therapy, intravenous fluid can be injected at the rate of 7 ml / kg of body weight for 20-30 minutes. An improvement in hemodynamics is observed as normal ventricular filling pressure and mean blood pressure are restored. It is necessary to pour colloidal solutions, as they more effectively restore both volume and oncotic pressure.

Of undoubted interest is the use of hypertonic solutions, since they are able to quickly restore the volume of plasma due to its extraction from the interstitium. Restoration of intravascular volume with crystalloids alone requires an increase in infusion by 2-3 times. At the same time, given the porosity of the capillaries, excessive hydration of the interstitial space contributes to the formation of pulmonary edema. Blood is transfused in such a way as to maintain the hemoglobin level in the range of 100-120 g / l or hematocrit of 30-35%. The total volume of infusion therapy is 30-45 ml / kg body weight, taking into account clinical (SBP, CVP, diuresis) and laboratory parameters.

Adequate fluid volume replacement is critical to improving tissue oxygen delivery. This indicator can be easily changed by optimizing CO and hemoglobin levels. During infusion therapy, diuresis should be at least 50 ml / h. If pressure continues to remain low after fluid volume replacement, dopamine is used at a dose of 10-15 μg / kg / min or dobutamine at a dose of 0.5-5 μg / (kg-min) to increase CO. If hypotension persists, correction with adrenaline at a dose of 0.1–1 μg / kg / min can be performed. The adrenergic vasopressor effect of epinephrine may be required in patients with persistent hypotension while using dopamine or in those who only respond to high doses. Due to the danger of deteriorating oxygen transport and consumption, adrenaline can be combined with vasodilators (nitroglycerin 0.5-20 μg / kg / min, nanipruss 0.5-10 μg / kg / min). In the treatment of severe vasodilation observed in septic shock, powerful vasoconstrictors should be used, for example, norepinephrine from 1 to 5 μg / kg / min or dopamine at a dose of more than 20 μg / kg / min.

Vasoconstrictors can have harmful effects and should be used to restore OPSS to normal limits of 1100-1200 dyn s / cm 5 m 2 only after BCC optimization. Digoxin, glucagon, calcium, calcium channel antagonists should be used strictly individually.

Respiratory therapy is indicated for patients with septic shock. Breathing support relieves the load on the DO 2 system and reduces the oxygen cost of breathing. Gas exchange improves with good oxygenation of the blood, therefore, oxygen therapy, ensuring airway patency and improving the drainage function of the tracheobronchial tree are always required. It is necessary to maintain RaOz at a level of at least 60 mm Hg, and a hemoglobin saturation of at least 90%. The choice of a method for treating ARF in septic shock depends on the degree of disturbance of gas exchange in the lungs, the mechanisms of its development and signs of excessive load on the respiratory apparatus. With the progression of respiratory failure, the method of choice is mechanical ventilation in the PEEP mode.

In the treatment of septic shock, special attention is paid to improving blood circulation and optimizing microcirculation. For this, rheological infusion media are used (reopolyglucin, plasmasteril, HAES-steril, reogluman), as well as courantil, complamin, trental, etc.

Metabolic acidosis can be corrected if the pH is below 7.2. however, this position remains controversial, since sodium bicarbonate can aggravate acidosis (shift of EDV to the left, ionic asymmetry, etc.).

In the process of intensive therapy, coagulation disorders should be eliminated, since septic shock is always accompanied by DIC.

The most promising are therapeutic measures,

aimed at starting, initial, septic shock cascades. It is advisable to use antioxidants (tocopherol, ubiquinone) as protectors of damage to cellular structures, and antienzyme drugs (gordox - 300,000-500,000 U, contrikal - 80,000-150,000 U, trasilol - 125,000-200,000 U) to inhibit blood proteases ). It is also necessary to use agents that weaken the effect of humoral factors of septic shock - antihistamines (suprastin, tavegil) in the maximum dose.

The use of glucocorticoids for septic shock is one of the controversial issues in the treatment of this condition. Many researchers believe that it is necessary to prescribe large doses of corticosteroids, but only once. In each case, an individual approach is required, taking into account the patient's immunological status, the stage of shock and the severity of the condition. We believe that the use of steroids of high activity and duration of action, which have less pronounced side effects, may be justified. These drugs include the corticosteroids dexamethasone and betamethasone.

In conditions of infusion therapy, along with the task of maintaining water-electrolyte balance, the issues of energy and plastic provision are necessarily resolved. Energy nutrition should be at least 200-300 g of glucose (with insulin) per day. The total calorie content of parenteral nutrition is 40-50 kcal / kg of body weight per day. Multicomponent parenteral nutrition should only be started after the patient is out of septic shock.

K. Martin et al. (1992) developed a scheme for the correction of hemodynamics in septic shock, which provides an effective therapy for circulatory and oxygen transport disorders and can be used in practice.

Rational correction of hemodynamics.

The following principal therapeutic objectives must be completed within 24-48 hours.

Required:

• SI not less than 4.5 l / (min-m 2);
• level DO 2 not less than 500 ml / (min-m 2);
• average blood pressure not less than 80 mm Hg;
• OPSS within 1100-1200 dyne-sDsm ^ m 2).

If possible:

• oxygen consumption level not less than 150 ml / (min-m 2);
• diuresis not less than 0.7 ml / (kg'h).

This requires:

1) to replenish the BCC to normal values, to provide PaO2 in arterial blood of at least 60 mm Hg, saturation - at least 90%, and the hemoglobin level - 100-120 g / l;

2) if SI is not less than 4.5 l / (min-m 2), you can limit yourself to monotherapy with norepinephrine at a dose of 0.5-5 μg / kg / min. If the SI level is below 4.5 l / (min-m 2), dobutamine is added additionally;

3) if the SI is initially less than 4.5 l / (min-m 2), it is necessary to start treatment with dobutamine at a dose of 0.5-5 μg / (kg-min). Norepinephrine is added when the mean blood pressure remains below 80 mm Hg;

4) in doubtful situations, it is advisable to start with norepinephrine, and, if necessary, supplement therapy with dobutamine;

5) epinephrine, isoproterenol, or inodilators can be combined with dobutamine to control CO levels; for the correction of OPSS, dopa-min or epinephrine can be combined with norepinephrine;

6) in the case of oliguria, use furosemide or small doses of dopamine (1-3 μg / kg-min);

7) every 4-6 hours it is necessary to control the oxygen transport parameters, and also to correct the treatment in accordance with the final goals of therapy;

8) cancellation of vascular support can be started after 24-36 hours of the period of state stabilization. In some cases, it may take several days for the complete withdrawal of vascular drugs, especially norepinephrine. In the first days, the patient, in addition to the daily physiological need, should receive 1000-1500 ml of fluid as compensation for the vasodilation that occurs after the abolition of α-agonists.

Thus, septic shock is a rather complex pathophysiological process that requires both in the diagnosis and in the treatment of an conscious rather than a stereotyped approach. The complexity and interconnectedness of pathological processes, the variety of mediators in septic shock create many problems in choosing an adequate therapy for this formidable complication of many diseases.

Submitted by J. Gomez et al. (1995), Mortality due to septic shock. despite rational intensive therapy, is 40-80 %.

The emergence of promising methods of immunotherapy and diagnostics opens up new treatment options that improve the outcome of septic shock. Encouraging results were obtained using monoclonal antibodies to the endotoxin nucleus and tumor necrosis factor.

Septic shock Is a systemic pathological reaction to a severe infection. It is characterized by fever, tachycardia, tachypnea, leukocytosis when identifying the focus of primary infection. In this case, a microbiological study of blood often reveals bacteremia. In some patients with sepsis syndrome, bacteremia is not detected. When arterial hypotension and multiple systemic insufficiency become components of the sepsis syndrome, the development of septic shock is noted.

Causes and pathogenesis of the development of septic shock:

The frequency of sepsis and septic shock has been steadily increasing since the thirties of the last century and, apparently, will continue to increase.
The reasons for this are:

1. The increasing use of invasive devices for intensive care, that is, intravascular catheters, etc.

2. 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.

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.

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 immune 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.

A critical deficiency of effectors causes multiple systemic failure.

Symptoms and signs of septic shock:

The development of a systemic inflammatory reaction is indicated by the presence of two or more of the following signs:

Body temperature is higher than 38 ° C, or below 36 ° C.

Respiratory rate is higher than 20 / minute. Respiratory alkalosis with arterial carbon dioxide tension below 32 mm Hg. Art.

Tachycardia with a heart rate greater than 90 / minute.

Neutrophilia with an increase in the content of polymorphonuclear leukocytes in the blood to a level above 12x10 9 / l, or neutropenia with a content of neutrophils in the blood at a level below 4x10 9 / l.

A shift in the leukocyte formula, in which stab neutrophils account for more than 10% of the total number of polymorphonuclear leukocytes.

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.

Septic shock course

In septic shock, hypercytokinemia increases the activity of nitric oxide synthetase in endothelial and other cells. As a result, the resistance of resistive vessels and venules decreases. A decrease in the tone of these microvessels reduces the total peripheral vascular resistance. Part of the body cells in septic shock suffer from ischemia caused by peripheral circulatory disorders. Disorders of peripheral circulation in sepsis and septic shock are consequences of systemic activation of endothelial cells, polymorphonuclear neutrophils and mononuclear phagocytes.

Inflammation of this genesis has a purely pathological character, occurs in all organs and tissues. 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.

According to traditional and correct views, sepsis and systemic inflammatory response causes the pathogenic effect of gram-negative microorganisms.

In the occurrence of a systemic pathological reaction to invasion of the internal environment and blood of gram-negative microorganisms, the decisive role is played by:

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 in the blood.

Receptor of the cell surface of mononuclear phagocytes and endothelial cells. Its specific element is a molecular complex consisting of LPS and LPSSP (LPS-LPSPS).

Currently, the frequency 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.

Previously, it was believed that septic shock is always caused by endotoxin (bacterial lipopolysaccharide), 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.

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.

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 the 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.

The following main links of the pathogenesis of peripheral circulatory disorders in septic shock are distinguished:

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 effects;

4) arterio-venular shunting;

5) drop in blood flow.

Hypovolemia is one of the factors of arterial hypotension in septic shock.

The following causes of hypovolemia (a drop in heart preload) in patients with septic shock are distinguished:

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.

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. With 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.

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.

Diagnosis of septic shock

• Septic shock - sepsis (systemic inflammatory response syndrome plus bacteremia) in combination with a decrease in blood pressure syst. less than 90 mm Hg Art. in the absence of apparent reasons for arterial hypotension (dehydration, bleeding). Signs of tissue hypoperfusion despite infusion therapy. Perfusion disorders include acidosis, oliguria, acute disturbances of consciousness. In patients receiving inotropic drugs, perfusion disorders may persist in the absence of arterial hypotension.
• Refractory septic shock - septic shock lasting more than one hour, refractory to fluid therapy.

Treatment for septic shock:

1. Infusion therapy

• Catheterization of two veins.
• 300-500 ml of crystalloid solution IV in the form of a bolus, then 500 ml of crystalloid solution IV drip for 15 minutes. Assess venous hypertension and the presence of cardiac decompensation.
• In the presence of heart failure, catheterization is advisable a. pulmonalis with a Swan-Ganz catheter to assess volemic status: optimal PCWP \u003d 12 mm Hg. Art. in the absence of AMI and 14-18 mm Hg. Art. in the presence of AMI;
• if after the infusion bolus the PCWP value exceeds 22 mmHg. Art., then one should assume the progression of heart failure and stop the active infusion of crystalloids.
• If, despite the high values \u200b\u200bof the filling pressure of the left ventricle, arterial hypotension persists - dopamine 1-3-5 or more mcg / kg / min, dobutamine 5-20 mcg / kg / min.
• Sodium bicarbonate in a calculated dose to correct metabolic acidosis.

2. Therapy of hypoxemia / ARDS - oxygen therapy, mechanical ventilation using PEEP.

3. Therapy of reduced contractile ability of the myocardium - strophanthin K 0.5 mg 1-2 times a day intravenously in 10-20 ml of 5-20% glucose solution or saline; digoxin 0.25 mg 3 times a day per os for 7-10 days, then 0.25-0.125 mg per day; dobutamine 5-20 mcg / kg / min IV.

4. Internal combustion engine therapy

5. ARF therapy.

6. Empirical antibiotic therapy (taking into account the localization of the source of the septic process and the expected range of possible microorganisms).

7. Surgical drainage of foci of infection.

8. Drugs, the effectiveness of which has not been confirmed:

• Naloxone.
• Corticosteroids.

Pathological condition, which has long been known as blood poisoning, is now called septic shock. Shock develops due to disseminated bacterial infection, in which an infectious agent is transferred by blood from one tissue to another, causing inflammation of various organs and intoxication. There are types of septic shock, due to the specific action of different types of bacterial infection.

Representation about septic shock is of great clinical importance, since along with cardiogenic shock, it is the most common cause of death in patients in a hospital in shock.

The most common causes of septic shock are as follows.
1. Peritonitis caused by infectious processes in the uterus and fallopian tubes, including those resulting from instrumental abortion performed in non-sterile conditions.
2. Peritonitis caused by damage to the wall of the gastrointestinal tract, including those arising from intestinal diseases or injuries.

3. Sepsis resulting from infectious skin lesions by streptococcal or staphylococcal microflora.
4. A common gangrenous process caused by a specific anaerobic pathogen, first in peripheral tissues, and then in internal organs, especially in the liver.
5. Sepsis resulting from infection of the kidneys and urinary tract, caused most often by E. coli.

Features of septic shock... Typical manifestations of septic shock of various origins are as follows.
1. Severe fever.
2. Widespread dilation of blood vessels, especially in infected tissues.

3. An increase in cardiac output in more than half of patients caused by the expansion of arterioles, which occurs in connection with general vasodilation, as well as in connection with an increase in the metabolic rate under the influence of bacterial toxins and high temperature.
4. Changes in the rheological properties of blood ("thickening") caused by the adhesion of erythrocytes in response to tissue degeneration.
5. Formation of microthrombi in the vascular bed - a condition characterized as disseminated intravascular coagulation (DIC syndrome). Since coagulation factors are involved in this process, a deficiency of coagulation factors is formed in the remaining circulating blood. In this regard, bleeding is observed in many tissues, especially in the gastrointestinal tract.

Early stages of septic shock against the background of a bacterial infection, symptoms of circulatory collapse do not appear. If the infectious process progresses, the circulatory system is involved due to both the direct action of the infectious principle and the secondary action, namely intoxication, leading to damage to the capillary wall and the release of plasma from the capillaries into the tissues. Then comes the moment from which hemodynamic disturbances develop in the same way as during other types of shock. The final stages of septic shock do not differ significantly from the final stages of hemorrhagic shock, even though the causes of these two conditions are completely different.

- This is a serious pathological condition that occurs with massive intake of bacterial endotoxins into the blood. It is accompanied by tissue hypoperfusion, a critical decrease in blood pressure and symptoms of multiple organ failure. The diagnosis is made on the basis of a general clinical picture, which combines signs of damage to the lungs, cardiovascular system (CVS), liver and kidneys, and centralization of blood circulation. Treatment: massive antibiotic therapy, infusion of colloidal and crystalloid solutions, maintenance of the cardiovascular system through the introduction of vasopressors, correction of respiratory disorders by mechanical ventilation.

ICD-10

R57.2

General information

The reasons

In the vast majority of cases, pathology develops against the background of a weakening of immune reactions. This occurs in patients with chronic severe illnesses, as well as in the elderly. Due to physiological characteristics, sepsis is more often diagnosed in men. The list of the most common diseases in which symptoms of ITS may occur include:

• Foci of purulent infection. Signs of a systemic inflammatory reaction and related disorders in the work of internal organs are noted in the presence of volumetric abscesses or phlegmon of soft tissues. The risk of a generalized toxic response increases with a long course of the disease, the absence of adequate antibiotic therapy and the patient's age over 60 years.
• Long stay in the ICU. Hospitalization in the intensive care unit is always associated with the risk of sepsis and infectious shock. This is due to constant contact with microflora resistant to antibacterial drugs, weakening of the body's defenses as a result of a serious illness, the presence of multiple infection gates: catheters, gastric tubes, drainage tubes.
• Wounds. Violations of the integrity of the skin, including those that occurred during the operation, significantly increase the risks of infection with highly contagious flora. ITSH begins in patients with contaminated wounds who have not received timely assistance. Tissue trauma during surgery becomes the cause of generalized infection only if the rules of asepsis and antisepsis are not followed. In most cases, septic shock occurs in patients who have undergone manipulations on the stomach and pancreas. Another common cause is diffuse peritonitis.
• Taking immunosuppressants.Medicines that suppress the immune system (mercaptopurine, chrysanol) are used to suppress the rejection reaction after organ transplantation. To a lesser extent, the level of self-protection decreases with the use of chemotherapeutic agents - cytostatics, intended for the treatment of cancer (doxorubicin, fluorouracil).
• AIDS. HIV infection in the AIDS stage leads to the development of atypical sepsis, provoked not by a bacterial culture, but by a fungus of the genus Candida. The clinical manifestations of the disease are characterized by a low degree of severity. The lack of an adequate immune response allows the pathogenic flora to multiply freely.

The causative agent of sepsis is gram-positive (streptococci, staphylococci, enterococci) and gram-negative (Enterobacter cloacae, Clostridium pneumoniae) bacteria. In many cases, cultures are insensitive to antibiotics, making it difficult to treat patients. Septic shock of viral origin is currently controversial among specialists. Some representatives of the scientific world argue that viruses are unable to cause pathology, others that an extracellular form of life can provoke a systemic inflammatory response, which is the pathogenetic basis of ITS.

Pathogenesis

The symptoms are based on the uncontrolled spread of inflammatory mediators from the pathological focus. In this case, the activation of macrophages, lymphocytes and neutrophils occurs. Systemic inflammatory response syndrome occurs. Against this background, the peripheral vascular tone decreases, the volume of circulating blood decreases due to an increase in vascular permeability and stagnation of fluid in the microcirculatory bed. Further changes are due to a sharp decrease in perfusion. Insufficient blood supply causes hypoxia, ischemia of internal organs and dysfunctions. The most sensitive is the brain. In addition, the functional activity of the lungs, kidneys and liver deteriorates.

In addition to SVR, endogenous intoxication plays an important role in the formation of septic shock. In connection with a decrease in the performance of excretory systems in the blood, products of normal metabolism accumulate: creatinine, urea, lactate, guanine and pyruvate. In internal media, the concentration of intermediate results of lipid oxidation (skatole, aldehydes, ketones) and bacterial endotoxins increases. All this causes severe changes in homeostasis, disorders of acid-base balance, disturbances in the functioning of receptor systems.

Classification

The state of shock is classified according to pathogenetic and clinical principles. Pathogenetically, the disease can be "warm" and "cold". Warm shock is characterized by an increase in cardiac output against the background of a decrease in general vascular tone, endogenous hypercatecholaminemia, and intradermal vasodilation. The phenomena of organ failure are moderately expressed. The cold variety is manifested by a decrease in cardiac output, a sharp weakening of tissue perfusion, centralized circulation, and severe MO. According to the clinical course, septic shock is divided into the following types:

1. Compensated. Consciousness is clear, intact, the patient is inhibited, but completely in contact. Arterial pressure is slightly reduced, the SBP level is not less than 90 mm Hg. Tachycardia is detected (PS<100 уд/мин). Субъективно пациент ощущает слабость, головокружение, головную боль и снижение мышечного тонуса.
2. Subcompensated. The skin is pale, the heart sounds are muffled, the heart rate reaches 140 beats per minute. GARDEN<90 мм. рт. ст., Дыхание учащенное, одышка до 25 движений/мин. Сознание спутанное, больной с задержкой отвечает на вопросы, плохо понимает, что происходит вокруг, где он находится. Речь тихая, медленная, неразборчивая.
3. Decompensated. Expressed depression of consciousness. The patient answers in monosyllables, in a whisper, often with 2-3 attempts. There is practically no motor activity, the reaction to pain is weak. The skin is cyanotic, covered with clammy cold sweat. Heart sounds are muffled, the pulse in the peripheral arteries is undetectable or sharply weakened. NPV up to 180 beats / min, heart rate 25-30, shallow breathing. BP is below 70/40, anuria.
4. Terminal (irreversible). Consciousness is absent, the skin is marbled or gray, covered with cyanotic spots. Breathing is pathological, like Biot or Kussmaul, NPV decreases to 8-10 times / minute, sometimes breathing stops completely. SBP less than 50 mm Hg. pillar. There is no urination. The pulse is hardly palpable even on the central vessels.

Symptoms of septic shock

One of the defining signs of ISS is arterial hypotension. It is not possible to restore the blood pressure level even with an adequate infusion volume (20-40 ml / kg). To maintain hemodynamics, it is necessary to use pressor amines (dopamine). Acute oliguria is noted, diuresis does not exceed 0.5 ml / kg / hour. The body temperature reaches febrile values \u200b\u200b- 38-39 ° C, poorly reduced with the help of antipyretics. To prevent seizures caused by hyperthermia, physical methods of cooling have to be used.

90% of cases of SH is accompanied by respiratory failure of varying severity. Patients with decompensated and terminal disease require respiratory support. The liver and spleen are enlarged, hardened, their function is impaired. There may be intestinal atony, flatulence, stools mixed with mucus, blood and pus. In the later stages, symptoms of disseminated intravascular coagulation occur: petechial rash, internal and external bleeding.

Complications

Septic shock leads to a number of severe complications. The most common of them is considered multiple organ failure, in which the function of two or more systems is impaired. First of all, the central nervous system, lungs, kidneys and heart are affected. Damage to the liver, intestines and spleen is somewhat less common. Mortality among patients with POI reaches 60%. Some of them die 3-5 days after removal from a critical state. This is due to organic changes in internal structures.

Bleeding is another common consequence of TSS. With the formation of intracerebral hematomas, the patient develops a clinic of acute hemorrhagic stroke. The accumulation of extravasate in other organs can lead to their compression. A decrease in blood volume in the vascular bed potentiates a more significant decrease in blood pressure. DIC against the background of infectious toxic shock causes the death of the patient in 40-45% of cases. Secondary organ damage provoked by microthrombosis that occurs at the initial stage of coagulopathy formation is observed in almost 100% of patients.

Diagnostics

Treatment for septic shock

Intensive therapy is indicated for patients. The treatment is carried out in the ICU departments using the methods of hardware and drug support. The attending physician is a resuscitator. Consultation of an infectious disease specialist, cardiologist, gastroenterologist and other specialists may be required. It is required to transfer the patient to artificial lung ventilation, round-the-clock supervision of nurses, parenteral feeding. Mixtures and products intended for administration to the stomach are not used. All methods of exposure are conventionally divided into pathogenetic and symptomatic:

• Pathogenetic treatment. If sepsis is suspected, the patient is prescribed antibiotics. The scheme should include 2-3 drugs of various groups with a wide spectrum of action. The selection of a medication at the initial stage is carried out empirically, in accordance with the expected sensitivity of the pathogen. At the same time, blood is taken for sterility and susceptibility to antibiotics. The analysis result is prepared within 10 days. If by this time it was not possible to select an effective drug regimen, research data should be used.
• Symptomatic treatment. It is selected taking into account the existing clinical picture. Usually, patients receive massive infusion therapy, glucocorticosteroids, inotropic agents, antiplatelet agents or hemostatics (depending on the state of the blood coagulation system). In severe cases, blood preparations are used: fresh frozen plasma, albumin, immunoglobulins. If the patient is conscious, administration of analgesic and sedative drugs is indicated.

Forecast and prevention

Septic shock has a poor prognosis for life. With a subcompensated course, about 40% of patients die. Decompensated and terminal types result in the death of 60% of patients. In the absence of timely medical care, mortality reaches 95-100%. Some patients die a few days after the pathological condition is eliminated. Prevention of ITS consists in the timely relief of foci of infection, competent selection of antibiotic therapy in surgical patients, compliance with antiseptic requirements in departments dealing with invasive manipulations, and support of an adequate immune status in representatives of the HIV-infected stratum of the population.