Treatment of septic shock. Septic shock - causes and pathogenesis. bacteremia and sepsis

Symptoms often begin with chills and include fever and hypotension, oliguria, and confusion. May be observed acute insufficiency several organs such as the lungs, kidneys, and liver. Treatment is intensive fluid therapy, antibiotics, surgical removal of infected or necrotic tissue and pus, supportive care, and sometimes blood glucose control and administration of corticosteroids.

Sepsis is an infection. Acute pancreatitis and serious injury, including burns, may present with symptoms of sepsis. The inflammatory response is usually manifested by two or more symptoms:

• Temperature >38 °C or<36 °С.
• Heart rate >90 bpm.
• Respiratory rate >20 per minute or PaCO 2<32 мм рт.ст.
• White blood cell count >12x109/l or<4х109/л или >10% immature forms.

However, at present, the presence of these criteria is only a suggestive factor and is not sufficient for making a diagnosis.

Severe sepsis is sepsis accompanied by signs of failure of at least one organ. Cardiovascular insufficiency, as a rule, is manifested by hypotension, respiratory failure - by hypoxemia.

Septic shock is severe sepsis with hypoperfusion and hypotension that is not relieved by adequate fluid resuscitation.

Causes of septic shock

Septic shock is more common in neonates, patients older than 35, and pregnant women. Predisposing factors include diabetes; cirrhosis of the liver; leukopenia.

Pathophysiology of septic shock

The pathogenesis of septic shock is not fully understood. Inflammatory agents (eg, bacterial toxin) lead to the production of mediators, including tumor necrosis factor and IL-1. These cytokines cause neutrophil-endothepial-cell adhesion, activate blood coagulation mechanisms and lead to the formation of microthrombi. They also promote the release of other mediators, including leukotrienes, lipoxygenase, histamine, bradykinin, serotonin, and IL-2. They are opposed by anti-inflammatory mediators such as IL-4 and IL-10 as a result of a negative feedback mechanism.

First, the arteries and arterioles dilate, and cardiac output increases. Later, cardiac output may decrease, blood pressure falls, and the typical signs of shock appear.

Even at the stage of increased cardiac output, vasoactive mediators cause blood flow to bypass the capillaries (distributive defect). Capillaries fall out of this shunt along with capillary obstruction by microthrombi, which reduces O2 delivery and reduces the excretion of CO2 and other waste products. Hypoperfusion leads to dysfunction.

Coagulopathy may develop due to intravascular coagulation involving major coagulation factors, increased fibrinolysis, and more often a combination of both.

Symptoms and signs of septic shock

In patients with sepsis, as a rule, there are: fever, tachycardia and tachypnea; BP remains normal. Other signs of infection are also usually present. Confusion may be the first sign of both severe sepsis and septic shock. BP usually drops, but paradoxically, the skin remains warm. There may be oliguria (<0,5 мл/кг/ч). Органная недостаточность приводит к появлению определенных дополнительных симптомов.

Diagnosis of septic shock

Sepsis is suspected when a patient with a known infection develops systemic symptoms of inflammation or organ dysfunction. If there are signs of systemic inflammation, the patient should be examined for infection. This requires a thorough study of the anamnesis, a physical examination and laboratory tests, including a general urinalysis and urine culture (especially in patients with indwelling catheters), blood cultures of suspicious body fluids. In severe sepsis, blood levels of procalcitonin and C-reactive protein are elevated and may facilitate diagnosis, but these values ​​are not specific. Ultimately, the diagnosis is based on the clinic.

Other causes of shock (eg, hypovolemia, myocardial infarction) should be identified by history, physical examination, ECG, and serum cardiac markers. Even without MI, hypoperfusion can lead to ECG evidence of ischemia, including nonspecific ST-T wave abnormalities, T-wave inversions, and supraventricular and ventricular premature beats.

Hyperventilation with respiratory alkalosis (low PaCO 2 and elevated blood pH) appears early as compensation for metabolic acidosis. Serum HSO; usually low, and serum lactate levels are elevated. Shock progresses, metabolic acidosis worsens, and blood pH decreases. Early respiratory failure leads to hypoxemia with Pa02<70 мм рт.ст. Уровень мочевины и креатинина обычно прогрессивно возрастают.

Nearly 50% of patients with severe sepsis develop relative adrenal insufficiency (i.e. normal or slightly elevated basal cortisol levels. Adrenal function can be checked by measuring serum cortisol at 8 am.

Hemodynamic measurements may be used when the type of shock is unclear or when large volumes of fluid are needed. Echocardiography (including transesophageal echocardiography) is the main method for assessing the functional state of the heart and the presence of vegetations.

Treatment of septic shock

• Infusion therapy with 0.9% saline.
• 02-therapy.
• Broad spectrum antibiotics.
• Drainage of abscesses and removal of necrotic tissue.
• Normalization of blood glucose levels.
• Replacement therapy with corticosteroids.

Patients with septic shock should be treated in an intensive care unit. Continuous monitoring of the following parameters is shown: system pressure; CVP, PAOR or both; pulse oximetry; ABGs; blood glucose, lactate and electrolyte levels; kidney function, and possibly sublingual PCO 2 . diuresis control.

If hypotension persists, dopamine may be given to increase mean blood pressure to at least 60 mmHg. If the dose of dopamine exceeds 20 mg/kg/min, another vasoconstrictor, usually norepinephrine, may be added. However, vasoconstriction caused by an increased dose of dopamine and norepinephrine poses a threat of both organ hypoperfusion and acidosis.

02 is given with a mask. Tracheal intubation and mechanical ventilation may be needed later if breathing is impaired.

Parenteral administration of antibiotics should be prescribed after taking blood, various media (fluids, body tissues) for sensitivity to antibiotics and culture. Early empiric therapy initiated immediately after sepsis is suspected is important and may be decisive. The choice of antibiotic should be justified, based on the suspected source, based on the clinical setting.

Treatment regimen for septic shock of unknown etiology: gentamicin or tobramycin, in combination with cephalosporins. Additionally, ceftazidime may be used in combination with fluoroquinolones (eg, ciprofloxacin).

Vancomycin should be added if resistant staphylococci or enterococci are suspected. If the source is localized in the abdominal cavity, a drug effective against anaerobes (for example, metronidazole) should be included in the therapy.

In corticosteroid therapy, replacement doses are used, not pharmacological ones. The regimen consists of hydrocortisone in combination with fludrocortisone for hemodynamic instability and for 3 consecutive days.

Sepsis is a pathological process, which is based on the reaction of the body in the form of a generalized (systemic)
inflammation for infection of various nature (bacterial, viral, fungal).

Synonyms: septicemia, septicopyemia.

ICD10 CODE
The usefulness of the etiological principle underlying the classification of sepsis in ICD10, from the standpoint of current knowledge and real clinical practice, seems to be limited. Orientation to bacteremia as the main diagnostic feature with low isolation of the pathogen from the blood, as well as the significant duration and laboriousness of traditional microbiological studies, make it impossible to widely use the etiological classification in practice (Table 31-1).

Table 31-1. Sepsis classification according to ICD-10

EPIDEMIOLOGY

Domestic data are not available. According to calculations, more than 700,000 cases of severe sepsis are diagnosed annually, i.e. about 2000 cases daily. Septic shock develops in 58% of cases of severe sepsis.

At the same time, sepsis was the main cause of death in non-coronary intensive care units and ranked 11th among all causes of mortality. Data on the prevalence of sepsis in different countries vary significantly: in the USA - 300 cases per 100,000 population (Angus D., 2001), in France - 95 cases per 100,000 population (Episepsis, 2004), in Australia and New Zealand - 77 per 100,000 population (ANZICS, 2004).

In the course of a multicenter epidemiological cohort prospective study covering 14,364 patients, 28 intensive care units in Europe, Israel and Canada, it was found that patients with sepsis accounted for 17.4% of cases (sepsis, severe sepsis, septic shock) of all patients who underwent through an intensive stage of treatment; at the same time, in 63.2% of cases it became a complication of nosocomial infections.

PREVENTION

Prevention of sepsis consists in the timely diagnosis and treatment of the underlying disease and the elimination of the source of infection.

SCREENING

A screening method for diagnosing a patient with a local focus of infection can be considered the criteria for systemic inflammatory response syndrome (see Classification).

CLASSIFICATION

The current classification of sepsis is based on the diagnostic criteria and classification proposed by the consensus conference of the American College of Pulmonologists and the Society for Critical Medicine Specialists (ACCP/SCCM). The issues of terminology and classification of sepsis were considered and approved at the Kaluga conciliation conference (2004) (Table 31-2).

Table 31-2. Classification and diagnostic criteria for sepsis

Local inflammation, sepsis, severe sepsis and multiple organ failure are links in the same chain in the body's response to inflammation due to microbial infection. Severe sepsis and septic (synonymous with infectious-toxic) shock constitute an essential part of the syndrome of the body's systemic inflammatory response to infection and become a consequence of the progression of systemic inflammation with the development of dysfunction of systems and organs.

BACTEREMIA AND SEPSIS

Bacteremia (the presence of infection in the systemic circulation) is one of the possible, but not mandatory, manifestations of sepsis. The absence of bacteremia should not affect the diagnosis in the presence of the above criteria for sepsis. Even with the most scrupulous observance of the technique of blood sampling and the use of modern technologies for the determination of microorganisms in the most severe patients, the frequency positive results usually does not exceed 45%. The detection of microorganisms in the bloodstream without clinical and laboratory evidence of a systemic inflammation syndrome should be regarded as transient bacteremia. The clinical significance of bacteremia may include the following:

• confirmation of the diagnosis and determination of the etiology of the infectious process;
• evidence of a mechanism for the development of sepsis (eg, catheter-related infection);
• rationale for choosing an antibiotic therapy regimen;
• assessment of the effectiveness of therapy.

The role of the polymerase chain reaction in the diagnosis of bacteremia and the interpretation of the results obtained remains unclear for practical application. The presence of a suspected or confirmed infectious process is established on the basis of the following signs:

• detection of leukocytes in body fluids that are normally sterile;
• perforation of a hollow organ;
• radiographic signs of pneumonia, the presence of purulent sputum;
• clinical syndromes in which the likelihood of an infectious process is high.

ETIOLOGY

To date, in most large medical centers, the frequency of gram-positive and gram-negative sepsis has been approximately equal. The sepsis caused by the fungal flora of the Candida type has ceased to be an exception. The risk of its occurrence is significantly increased in patients with a high index of severity of the general condition, a long stay in the intensive care unit (more than 21 days), who are on full parenteral nutrition, who received glucocorticoids; patients with severe renal dysfunction requiring extracorporeal detoxification.

The etiology of gynecological sepsis is determined by the source of infection:

Vaginal Source:
- Peptostreptococcus spp.;
- Bacteroides bivus;
- Streptococcus group B;
- Gardnerella vaginalis;
- Mycoplasma hominis;
-S. aureus.

Intestinal source:
―E. coli;
-Enterococcus spp.;
-Enterobacter spp.;
-Clostridium spp.;
-Bacteroides fragilis;
- Candida spp.

Sexually Transmissive:
-Neisseria gonorrhoeae;
-Chlamydia trachomatis.

Hematogenous:
- Listeria monocytogenes;
-Campylobacter spp.;
- Streptococcus group A.

PATHOGENESIS

The development of organ-system damage in sepsis is primarily associated with uncontrolled spread from the primary focus infectious inflammation pro-inflammatory mediators of endogenous origin with subsequent activation under their influence of macrophages, neutrophils, lymphocytes and a number of other cells in other organs and tissues, with secondary release of similar endogenous substances, damage to the endothelium and a decrease in organ perfusion and oxygen delivery. Dissemination of microorganisms may be absent altogether or be short-lived and subtle. However, even in such a situation, the release of pro-inflammatory cytokines at a distance from the focus is possible. Bacterial exo and endotoxins can also activate hyperproduction of cytokines from macrophages, lymphocytes, and endothelium.

The total effects exerted by mediators form a systemic inflammatory response syndrome. Three main stages began to be distinguished in its development.

1st stage. Local production of cytokines in response to infection.

A special place among inflammatory mediators is occupied by the cytokine network, which controls the processes of realization of immune and inflammatory reactivity. The main producers of cytokines are T cells and activated macrophages, as well as to some extent other types of leukocytes, endothelial cells of postcapillary venules, platelets and various types of stromal cells. Cytokines primarily act in the focus of inflammation and on the territory of reacting lymphoid organs, ultimately performing a number of protective functions, participating in the processes of wound healing and protecting body cells from pathogenic microorganisms.

2nd stage. Release of a small amount of cytokines into the systemic circulation.

Small amounts of mediators are able to activate macrophages, platelets, the release of adhesion molecules from the endothelium, and the production of growth hormone. The developing acute phase reaction is controlled by proinflammatory mediators (interleukins IL1, IL6, IL8, tumor necrosis factor α, etc.) and their endogenous antagonists, such as IL4, IL10, IL13, soluble TNFα receptors and others, called anti-inflammatory mediators. By maintaining a balance and controlled relationships between pro and anti-inflammatory mediators, under normal conditions, prerequisites are created for wound healing, the destruction of pathogenic microorganisms, and the maintenance of homeostasis. Systemic adaptive changes in acute inflammation include stress reactivity of the neuroendocrine system, fever, release of neutrophils into circulation from the vascular and bone marrow depots, increased leukocytopoiesis in the bone marrow, hyperproduction of acute phase proteins in the liver, and the development of generalized forms of the immune response.

3rd stage. Generalization of the inflammatory response.

With severe inflammation or its systemic failure, some types of cytokines: TNFα, IL1, IL6, IL10, TGFβ, INFγ (with viral infections) - can enter the systemic circulation, accumulate there in quantities sufficient to realize their long-range effects. If the regulatory systems are unable to maintain homeostasis, the destructive effects of cytokines and other mediators begin to dominate, which leads to impaired capillary permeability and endothelial function, the triggering of disseminated vascular coagulation syndrome, the formation of distant foci of systemic inflammation, and the development of mono and multiple organ dysfunction. Apparently, any violations of homeostasis that can be perceived as factors of systemic damage can also act as factors of systemic damage. immune system as damaging or potentially damaging.

At this stage of the systemic inflammatory response syndrome, from the standpoint of the interaction of pro and anti-inflammatory mediators, it is possible to conditionally distinguish two periods. The first, initial - period of hyperinflammation, characterized by the release of ultra-high concentrations of pro-inflammatory cytokines, nitric oxide, which is accompanied by the development of shock and the early formation of multiple organ failure syndrome (MOS). However, already at the moment there is a compensatory release of anti-inflammatory cytokines, the rate of their secretion, the concentration in the blood and tissues gradually increases with a parallel decrease in the content of inflammatory mediators.

A compensatory anti-inflammatory response develops, combined with a decrease in the functional activity of immunocompetent cells - a period of "immune paralysis". In some patients, due to genetic determination or reactivity changed under the influence of environmental factors, the formation of a stable anti-inflammatory reaction is immediately recorded.

Gram-positive bacteria do not contain cell membrane endotoxin and cause septic reactions through other mechanisms. Factors triggering a septic response can be cell wall components such as peptidoglycan and teichoic acid, staphylococcal protein A and streptococcal protein M located on the cell surface, glycocalyx, exotoxins. In this regard, the complex of reactions in response to invasion by gram-positive microorganisms is more complex. TNFα is a key pro-inflammatory mediator. The pivotal role of TNFα in the development of sepsis is associated with the biological effects of this mediator: an increase in the procoagulant properties of the endothelium, activation of neutrophil adhesion, induction of other cytokines, stimulation of catabolism, fever, and synthesis of "acute phase" proteins. The generalization of damaging effects is mediated by the wide prevalence of TNFα receptors and the ability of other cytokines to release it. From a practical point of view, it is important that the rate of reactions of the septic cascade increases sharply under hypoxic conditions due to the expression of cytokine receptors on the cell surface.

In the genesis of acute vascular insufficiency, which underlies septic shock syndrome, the leading role is given to nitric oxide, the concentration of which increases tenfold as a result of stimulation of macrophages TNFα, IL1, IFN, and further secretion of nitric oxide is also carried out by vascular smooth muscle cells, and the monocytes themselves are activated under it. action. Under normal conditions, nitric oxide plays the role of a neurotransmitter, is involved in vasoregulation, phagocytosis. Characteristically, microcirculation disorders in sepsis are heterogeneous: dilatation zones are combined with areas of vasoconstriction. Risk factors for developing septic shock - oncological diseases, the severity of the condition of patients on the SOFA scale more than 5 points, chronic obstructive pulmonary disease, old age.

As a result of dysfunction of the liver, kidneys, intestines, new factors of damaging effects appear distal to cytokines. These are intermediate and end products of normal metabolism in high concentrations (lactate, urea, creatinine, bilirubin), components and effectors of regulatory systems accumulated in pathological concentrations (kallikreinkinin, coagulation, fibrinolytic), products of perverted metabolism (aldehydes, ketones, higher alcohols). ), substances of intestinal origin such as indole, skatole, putrescine.

CLINICAL PICTURE

The clinical picture of sepsis consists of clinical picture systemic inflammatory response syndrome (tachycardia, fever or hypothermia, shortness of breath, leukocytosis or leukopenia with a shift in the leukocyte formula) and a variety of syndromes characteristic of organ dysfunction (septic encephalopathy, septic shock, acute respiratory, cardiac, renal, hepatic failure).

Septic encephalopathy is most often the result of cerebral edema and can be associated both with the development of a systemic inflammatory response syndrome and with the development of septic shock, hypoxia, concomitant diseases (cerebrovascular atherosclerosis, alcohol or drug addiction, etc.). The manifestations of septic encephalopathy are varied - anxiety, agitation, psychomotor agitation and, conversely, lethargy, apathy, lethargy, stupor, coma.

The appearance of acute respiratory failure in sepsis is most often associated with the development of acute lung injury or acute respiratory distress syndrome, the diagnostic criteria for which are hypoxemia, bilateral infiltrates on the x-ray, a decrease in the ratio of the partial pressure of oxygen in the arterial blood to the inspiratory fraction of oxygen (PaO2 / FiO2) below 300, no signs of left ventricular failure.

The development of septic shock is characterized by impaired peripheral circulation due to the development of dilatation of the capillary vascular bed. Skin acquire a marble shade, acrocyanosis develops; they are usually hot to the touch, high humidity, profuse sweat is characteristic, the extremities are warm, slowing down of the vascular spot is characteristic when pressing on the nail bed. AT late stages septic shock (phase of "cold" shock), the limbs are cold to the touch. Hemodynamic disturbances in septic shock are characterized by a decrease in blood pressure, which cannot be normalized during infusion therapy, tachycardia, a decrease in central venous pressure and pulmonary capillary wedge pressure. Respiratory failure progresses, oliguria, encephalopathy, and other manifestations of multiple organ dysfunction develop.

Assessment of organ dysfunction in sepsis is carried out according to the criteria below (Table 31-3).

Table 31-3. Criteria for organ dysfunction in sepsis

DIAGNOSTICS

ANAMNESIS

Anamnestic data in sepsis are most often associated with the presence of an unsanitized focus of infection of both the pelvic organs (endometritis, peritonitis, wound infection, criminal abortion) and other sources (pneumonia - 50%, abdominal infection - 19% of all causes of severe sepsis, pyelonephritis , endocarditis, ENT infections, etc.).

PHYSICAL EXAMINATION

The main purpose of the study is to establish the source of infection. In this regard, standard methods of gynecological and general clinical examination are used. There are no pathognomonic (specific) symptoms of sepsis. Diagnosis of sepsis is based on the criteria for a systemic inflammatory response and the presence of a focus of infection. The criteria for a focus of infection are one or more of the following:

• leukocytes in normally sterile biological fluids;
• perforation of a hollow organ;
• X-ray signs of pneumonia in combination with purulent sputum;
• the presence of a syndrome of high risk of infection (in particular cholangitis).

LABORATORY RESEARCH

Laboratory diagnostics is based on measuring the number of leukocytes (less than 4 or more than 12x109 / l), the appearance of immature forms (more than 10%), the assessment of the degree of organ dysfunction (creatinine, bilirubin, arterial blood gases).

High specificity for confirming the diagnosis of sepsis of bacterial etiology is the determination of the concentration of procalcitonin in the blood plasma (increase above 0.5-1 ng / ml is specific for sepsis, above 5.5 ng / ml - for severe sepsis of bacterial etiology - sensitivity 81%, specificity 94 %). ESR increase,

The reactive protein, due to its low specificity, cannot be recognized as a diagnostic marker of sepsis.

Negative blood culture results do not rule out sepsis. Blood for microbiological examination must be taken before antibiotics are prescribed. The required minimum sampling is two samples taken from the veins of the upper extremities with an interval of 30 minutes. It is optimal to take three blood samples, which significantly increases the possibility of detecting bacteremia. If necessary, material is taken for microbiological examination from the alleged source of infection (cerebrospinal fluid, urine, secretion of the lower respiratory tract, etc.).

INSTRUMENTAL STUDIES

Methods of instrumental diagnostics cover all the methods necessary to identify the source of infection. Methods of instrumental diagnostics in each case are determined by specialized specialists. To identify the source of infection of the uterine cavity, ultrasound of the uterus, hysteroscopy are performed; to identify a source in the abdominal cavity (uterine appendages) - abdominal ultrasound, computed tomography, magnetic resonance imaging, laparoscopy.

DIFFERENTIAL DIAGNOSIS

Differential diagnosis of sepsis includes almost all diseases accompanied by tachycardia, shortness of breath, hypotension, leukocytosis, and organ dysfunction. Most often in the practice of an obstetrician and gynecologist, a differential diagnosis is carried out with the following conditions:

• preeclampsia;
• pulmonary embolism;
• acute heart failure;
• acute myocardial infarction, cardiogenic shock;
• pulmonary edema;
• lung atelectasis;
• pneumothorax, hydrothorax;
• exacerbation of chronic obstructive pulmonary disease;
• acute renal failure;
• toxic liver damage;
• toxic encephalopathy;
• amniotic fluid embolism.

A differential diagnostic criterion confirming sepsis can be the concentration of procalcitonin in the blood plasma above 0.5 ng / ml, for severe sepsis - above 5.5 ng / ml.

INDICATIONS FOR CONSULTATION OF OTHER SPECIALISTS

If signs of organ dysfunction appear, a consultation with an anesthesiologist and resuscitator is indicated. In the absence of a focus of infection, consultations of specialized specialists (therapist, neurologist, otorhinolaryngologist, dentist, urologist, infectious disease specialist).

EXAMPLE FORMULATION OF THE DIAGNOSIS

Endometritis. Sepsis. Acute respiratory failure.

TREATMENT

Effective intensive care of sepsis is possible only under the condition of full surgical sanitation of the focus of infection and adequate antimicrobial therapy. Inadequate initial antimicrobial therapy is an independent risk factor for death in patients with sepsis. At the same time, maintaining the patient's life, preventing and eliminating organ dysfunction is impossible without targeted intensive therapy. Often the question arises of extirpation of the uterus, especially with its purulent melting, or the removal of a tubo-ovarian formation containing pus.

The main goal of this therapy is to optimize oxygen transport in conditions of its increased consumption, which is characteristic of severe sepsis and septic shock. This direction of treatment is implemented through hemodynamic and respiratory support. Other aspects of intensive care play an important role: nutritional support, immunoreplacement therapy, correction of hemocoagulation disorders, prevention of deep vein thrombosis and thromboembolic complications, prevention of stress and the occurrence of gastrointestinal bleeding in patients with sepsis.

ANTIBACTERIAL THERAPY

It is necessary to start antibiotic therapy in the first hours after the diagnosis of sepsis is established, based on the following principles:

• the range of suspected pathogens depending on the location of the primary focus;
• the level of resistance of nosocomial pathogens according to microbiological monitoring of a particular medical institution;
• conditions for the occurrence of sepsis - community-acquired or nosocomial;
• the severity of the patient's condition, assessed by the presence of multiple organ failure or APACHE II.

Evaluation of the effectiveness of ongoing antibiotic therapy is carried out no earlier than after 48-72 hours.

HEMODYNAMIC SUPPORT

Infusion therapy belongs to the initial measures to maintain hemodynamics and, above all, cardiac output. The main objectives of infusion therapy in patients with sepsis are: restoration of adequate tissue perfusion, normalization of cellular metabolism, correction of homeostasis disorders, reduction in the concentration of septic cascade mediators and toxic metabolites.

In sepsis with MOF and septic shock, it is necessary to strive to quickly achieve (the first 6 hours after admission) the target values ​​of the following parameters: central venous pressure 8–12 mm Hg, mean blood pressure more than 65 mm Hg, diuresis 0.5 ml/(kgxh), hematocrit over 30%, blood saturation in the superior vena cava or right atrium at least 70%. The use of this algorithm improves survival in septic shock and severe sepsis. The volume of infusion therapy should be maintained so that the wedge pressure in the pulmonary capillaries does not exceed the plasma colloidal oncotic pressure (to avoid pulmonary edema) and is accompanied by an increase in cardiac output. It is necessary to take into account the parameters characterizing the gas exchange function of the lungs - PaO2 and PaO2 / FiO2, the dynamics of the x-ray picture.

For infusion therapy in the targeted intensive care of sepsis and septic shock, crystalloid and colloid infusion solutions are used with almost the same result. All infusion media have both their advantages and disadvantages. Taking into account the available results of experimental and clinical studies to date, there is no reason to give preference to any of the infusion media.

The qualitative composition of the infusion program should be determined by the characteristics of the patient: the degree of hypovolemia, the phase of the syndrome of disseminated intravascular coagulation, the presence of peripheral edema and the level of blood albumin, the severity of acute pulmonary injury.

Plasma substitutes (dextrans, gelatin preparations, hydroxyethyl starches) are indicated for severe deficiency of circulating blood volume. Hydroxyethyl starches with a molecular weight of 200/0.5 and 130/0.4 have a potential advantage over dextrans due to a lower risk of membrane escape and no clinically significant effect on hemostasis. Albumin transfusion will be useful only if albumin levels fall below 20 g/l and there are no signs of "leakage" into the interstitium. The use of fresh frozen plasma is indicated for coagulopathy of consumption and a decrease in the coagulation potential of the blood. According to most experts, the minimum concentration of hemoglobin for patients with severe sepsis should be in the range of 90–100 g/l. The wider use of donor erythrocyte mass should be limited due to the high risk of developing various complications (acute lung injury, anaphylactic reactions, etc.).

Low perfusion pressure requires the immediate inclusion of drugs that increase vascular tone and / or inotropic function of the heart. Dopamine or norepinephrine are the drugs of first choice for the treatment of hypotension in patients with septic shock.

Dobutamine should be considered as the drug of choice for increasing cardiac output and oxygen delivery at normal or elevated levels of preload. Due to the predominant action on β1-receptors, dobutamine to a greater extent than dopamine contributes to the improvement of these indicators.

RESPIRATORY SUPPORT

The lungs very early become one of the first target organs involved in the pathological process in sepsis.

Acute respiratory failure is one of the leading components of multiple organ dysfunction. Its clinical and laboratory manifestations in sepsis correspond to the syndrome of acute lung injury, and with the progression of the pathological process - to acute respiratory distress syndrome. Indications for mechanical ventilation in severe sepsis are determined by the development of parenchymal respiratory failure: with a decrease in the respiratory index below 200, tracheal intubation and the beginning of respiratory support are indicated. With a respiratory index above 200, indications are determined on an individual basis. The presence of adequate consciousness, the absence of high costs for the work of breathing, severe tachycardia (heart rate up to 120 per minute), normalization of venous blood return and SaO2 > 90% against the background of oxygen support for spontaneous breathing completely allow one to refrain from transferring to artificial ventilation of the lungs, but not from strict control over the dynamics of the patient's condition. Optimal blood oxygen saturation levels (approximately 90%) can be maintained with a variety of oxygen therapies (face masks, nasal catheters) using a non-toxic oxygen concentration (FiO2<0,6). Больным с тяжёлым сепсисом противопоказано применение неинвазивной респираторной поддержки.

It is necessary to adhere to the concept of safe mechanical ventilation, according to which it is slightly aggressive under the following conditions: peak airway pressure below 35 cm of water column, inspiratory oxygen fraction below 60%, tidal volume less than 10 ml/kg, non-inverted inspiratory ratio to exhale. The selection of the parameters of the respiratory cycle is carried out until the criteria for the adequacy of artificial lung ventilation are reached: PaO2 is more than 60 mm Hg, SaO2 is more than 93%, PvO2 is 35–45 mm Hg, SvO2 is more than 55%.

NUTRITIONAL SUPPORT

The development of PON syndrome in sepsis is usually accompanied by manifestations of hypermetabolism. In this situation, energy needs are covered due to the destruction of one's own cellular structures, which aggravates the existing organ dysfunction and enhances endotoxicosis. Nutritional support is considered as a method that prevents the development of severe malnutrition (protein-energetic insufficiency) against the background of pronounced hypercatabolism and hypermetabolism, which are the most characteristic metabolic characteristics of a generalized inflammatory reaction of an infectious origin. Inclusion of enteral nutrition in the complex

intensive care prevents the translocation of microflora from the intestine, the development of dysbacteriosis, increases the functional activity of the enterocyte and the protective properties of the mucous membrane, reducing the degree of endotoxicosis and the risk of secondary infectious complications.

When conducting nutritional support, it is advisable to focus on the following recommendations:

• energy value of food: 25–30 kcal/(kgxday);
• protein: 1.3–2.0 g/(kgxday);
• Glucose: 30-70% non-protein calories while maintaining glycemic levels below 6.1 mmol/L;
• lipids: 15–20% of non-protein calories.

Early start of nutritional support within 24-36 hours is more effective than with 3-4 days of intensive therapy.

This is especially true for protocols for early and late start of enteral tube feeding.

For effective synthesis of endogenous protein, it is important to maintain a metabolic ratio of non-protein calories / total nitrogen in the range of 1 g of nitrogen to 110–130 kilocalories. Carbohydrates do not need to be administered at a dose of more than 6 g / (kg x day) due to the fact that there is a risk of developing hyperglycemia and activation of catabolism processes in skeletal muscles. With parenteral administration of fat emulsions, a round-the-clock regimen is recommended. It is necessary to give preference to 2nd generation fat emulsions of the MCT/LCT type, which demonstrate a higher rate of utilization from the bloodstream and oxidation in patients with severe sepsis.

Contraindications for nutritional support:

• refractory shock syndrome (dose of dopamine more than 15 mcg / (kgxmin) and systolic blood pressure less than 90 mm Hg);
• intolerance to media for nutritional support;
• severe intractable arterial hypoxemia;
• severe uncorrected hypovolemia;
• decompensated metabolic acidosis.

GLYCEMIA CONTROL

An important aspect of complex intensive care for severe sepsis is constant monitoring of glycemic levels and insulin therapy. A high level of glycemia and the need for insulin therapy are factors of an unfavorable outcome in patients diagnosed with sepsis. In this regard, it is necessary to strive to maintain the level of glycemia within 4.5–6.1 mmol/l. At a glycemia level of more than 6.1 mmol/l, insulin infusion (at a dose of 0.5–1 U/hour) should be performed to maintain normoglycemia (4.4–6.1 mmol/l). Control of glucose concentration - every 1-4 hours, depending on the clinical situation. When this algorithm is executed, a statistically significant increase in survival is recorded.

GLUCOCORTICOIDS

Glucocorticoids in sepsis are used according to the following indications:

• the use of high doses of glucocorticoids in the treatment of septic shock is inappropriate due to the lack of an effect on increasing survival and an increased risk of nosocomial infections;
• the addition of hydrocortisone at doses of 240-300 mg/day for 5-7 days to the complex therapy of septic shock can accelerate the moment of stabilization of hemodynamics, the abolition of vascular support and increase survival in the population of patients with concomitant relative adrenal insufficiency.

It is necessary to abandon the chaotic empirical prescription of prednisolone and dexamethasone. In the absence of laboratory evidence of the development of relative adrenal insufficiency, the use of hydrocortisone at a dose of 300 mg / day (for 3-6 injections) should be resorted to in refractory septic shock or when high doses of vasopressors are required to maintain effective hemodynamics. The effectiveness of hydrocortisone in septic shock can be mainly associated with the following mechanisms of action of glucocorticoids in conditions of systemic inflammation: activation of the nuclear factor inhibitor and correction of relative adrenal insufficiency. In turn, inhibition of nuclear factor activity leads to a decrease in the synthesis of inducible NO synthetase (nitric oxide is the most powerful endogenous vasodilator), as well as the formation of pro-inflammatory cytokines, cyclooxygenase, and adhesion molecules.

ACTIVATED PROTEIN C

One of the characteristic manifestations of sepsis is a violation of systemic coagulation (activation of the coagulation cascade and inhibition of fibrinolysis), which ultimately leads to hypoperfusion and organ dysfunction. The effect of activated protein C on the inflammatory system is realized through several mechanisms:

• decrease in the attachment of selectins to leukocytes, which is accompanied by the preservation of the integrity of the vascular endothelium, which plays a crucial role in the development of systemic inflammation;
• decreased release of cytokines from monocytes;
• blocking the release of TNFα from leukocytes;
• inhibition of thrombin production, which potentiates the inflammatory response.

Anticoagulant, profibrinolytic and anti-inflammatory action due to:

• degradation of factors Va and VIIIa, which leads to the suppression of thrombus formation;
• activation of fibrinolysis due to suppression of the plasminogen activator inhibitor;
• direct anti-inflammatory effect on endothelial cells and neutrophils;
• protecting the endothelium from apoptosis.

Administration of activated protein C (drotrecogin alfa [activated]) at a dose of 24 μg/(kg h) for 96 hours reduces the risk of death by 19.4%.

IMMUNOGLOBULIN INFUSION

The expediency of prescribing an infusion of immunoglobulins (IgG and IgG + IgM) is associated with their ability to limit the excessive action of pro-inflammatory cytokines, increase the clearance of endotoxin and staphylococcal superantigen, eliminate anergy, enhance the effect of beta-lactam antibiotics. The use of immunoglobulins in the framework of immunoreplacement therapy for severe sepsis and septic shock is currently recognized as the only really proven method of immunocorrection that increases survival in sepsis. The best effect was registered when using a combination of IgG and IgM. The standard dosing regimen is to administer 3–5 ml/(kg · day) for three consecutive days. Optimal results with the use of immunoglobulins were obtained in the early phase of shock (“warm shock”) and in patients with severe sepsis and the APACH II severity index range of 20–25 points.

PREVENTION OF DEEP VEIN THROMBOSIS

The available data now confirm that the prevention of deep vein thrombosis significantly affects the outcome of the treatment of patients with sepsis. For this purpose, both unfractionated heparin and low molecular weight heparin preparations can be used. The main advantages of low molecular weight heparin preparations are a lower incidence of hemorrhagic complications, a less pronounced effect on platelet function, a prolonged action, i.e. the possibility of a single administration per day.

PREVENTION OF FORMATION OF STRESS IN THE GASTROINTESTINAL TRACT

This direction plays a significant role in a favorable outcome in the management of patients with severe sepsis and septic shock, since mortality in patients with bleeding from gastrointestinal stress ranges from 64 to 87%. The frequency of occurrence of stress disorders without their prevention in critically ill patients can reach 52.8%. Prophylactic use of H2 receptor blockers and proton pump inhibitors reduces the risk of complications by 2 times or more. The main direction of prevention and treatment is maintaining a pH above 3.5 (up to 6.0). At the same time, the effectiveness of proton pump inhibitors is higher than the use of H2 blockers. It should be emphasized that, in addition to the above drugs, enteral nutrition plays an important role in preventing the formation of stress disorders.

RENAL REPLACEMENT THERAPY

Kidney dysfunction causes rapid decompensation of organ failure due to an increase in endotoxemia due to the development of a systemic inflammatory response syndrome, massive cytolysis, pathological proteinolysis, leading to the development of pronounced water-sector disorders with generalized damage to the endothelium, impaired hemocoagulation and fibrinolysis, an increase in the permeability of the capillary bed and, as a result, to rapid decompensation (or manifestation) of organ failure (cerebral edema, acute lung injury, distress syndrome, distributive shock and acute cardiac, hepatic and intestinal failure).

The main difference between isolated renal failure (acute or chronic) and acute renal failure in PON is in the spectrum of endotoxins formed and accumulated in the body. In isolated renal failure, they are represented by substances of small molecular weight (less than 1000 D) - urea, indoles, phenols, polyamines, neopterins, ammonia, uric acid. These substances can be effectively eliminated by hemodialysis. With PON, substances of medium and high molecular weight (more than 1000 D) are added to the above spectrum of low molecular weight toxins, which include all biologically active substances formed as a result of a systemic inflammatory reaction - TNFα, interleukins, leukotrienes, thromboxane, oligopeptides, complement components. With respect to these substances, hemodialysis is not effective, and preference is given to convection mass transfer, used in hemofiltration, and a combination of the two methods described above in hemodiafiltration. These methods allow, albeit with some reservations, to remove substances with a molecular weight of up to 100,000 D. These include plasma proteins, including immunoglobulins, circulating immune complexes containing complement and myoglobin, although the clearance of these chemical compounds is much higher when using plasma filtration methods.

Despite the foregoing pathophysiological database of treatments, there are currently no extensive and well-controlled studies supporting renal replacement therapy as an integral part of targeted therapy for severe sepsis. Moreover, even when using the most pathogenetically substantiated of them method - venovenous prolonged hemofiltration (speed 2 l/h for 48 hours) - no decrease in blood IL6, IL8, TNFα and mortality were observed. In this regard, its use in wide practice has not yet been justified and is indicated only in the development of acute renal failure.

FORECAST

Mortality in severe sepsis is about 20% with mono-organ dysfunction, increasing to 80–100% when four or more organs are involved.

BIBLIOGRAPHY
Abdominal surgical infection: clinic, diagnostics, antimicrobial therapy: pract. hands / Under the editorship of V.S. Savelyeva, B.R. Gelfand. - M.: Literra, 2006. - 168 p.
Gelfand B.R., Kirienko P.A., Grinenko T.F. and others. Anesthesiology and Intensive Care: Prakt. hands / Under the total. ed.B.R. Gelfand. - M.: Literra, 2005. - 544 p.
Sepsis at the beginning of the XXI century. Classification, clinical diagnostic concept and treatment. Pathological anatomical diagnostics: pract. hands - M.: Literra, 2006. - 176 p.
Surgical infections: pract. hands / Ed. I.A. Eryukhina and others: ed. 2e, per. and additional - M.: Literra, 2006. - 736 p.
Bone R.C., Balk R.A., Cerra F.B. Definitions for sepsis and organ failure and guidelines for the use of innovative therapies in sepsis: the ACCP/SCCM consensus conference committee // Chest. - 1992. - Vol. 101. - P. 1644-1655.

Septic shock is a severe complication of an infectious disease that can be life threatening. Septic shock is characterized by a decrease in tissue perfusion, which significantly impairs the delivery of oxygen and nutrients to the tissues. This condition leads to insufficiency of many internal organs, which poses a mortal threat to the patient. The probability of death in septic shock is 30 - 50%!

Often, septic shock is recorded in children, the elderly and in patients with severe immunodeficiency.

Septic shock - causes and development factors

Septic shock can be caused by various pathogens. Bacteria that cause septic shock generally belong to the class of endotoxin-producing bacteria. Often the following pathogenic microbes are the cause of septic shock:

• coli;
• aerobic and anaerobic streptococci;
• clostridia;
• bacteroids;
• beta-hemolytic streptococcus;
• golden staphylococcus aureus;
• klebsiella;
• other pathogenic microorganisms.

It is noteworthy that beta-hemolytic streptococcus and Staphylococcus aureus produce a specific virulent exotoxin that can cause toxic shock syndrome in a patient.

Septic shock (and sepsis) is an inflammatory response to some trigger. As a rule, it is a microbial endotoxin, less often it is an exotoxin. Endotoxins are specific substances (lipopolysaccharides) that are released during the lysis (destruction) of Gram-negative bacteria. These toxins activate specific immune mechanisms in the human body, which leads to the development of an inflammatory process. Exotoxins are substances that a gram-negative bacterium secretes to the outside.

Toxins enter the bloodstream and stimulate the production of inflammatory cytokines, including: tumor necrosis factor, interleukin-1, interleukin-8 in the vascular endothelium. This reaction leads to adhesion (sticking) of neutrophils, leukocytes, endotheliocytes with the formation of specific toxic substances.

Types of disease: classification of septic shock

The classification of septic shock is based on the localization of the pathology, the features of its course and the stage of compensation.

Depending on the localization of the pathological process, septic shock can be:

• pulmonary-pleural;
• intestinal;
• peritoneal;
• biliary;
• urodynamic or urinemic;
• obstetric or hysterogenic;
• skin;
• phlegmonous or mesenchymal;
• vascular.

Downstream, septic shock occurs:

• lightning fast (or instant);
• early or progressive;
• erased;
• recurrent (or septic shock with an intermediate stage);
• terminal (or late).

According to the stage of compensation, septic shock is divided into the following types:

• compensated;
• subcompensated;
• decompensated;
• refractory.

Symptoms of septic shock: how the disease manifests itself

Symptoms of septic shock largely depend on the pathogen, the state of the patient's immunity and the source of infection.

The onset of septic shock can be quite violent and be accompanied by symptoms such as:

• strong ;
• hemorrhagic or papular rash;
• gradual, slowly increasing intoxication;
• myalgia.

Common but non-specific symptoms of sepsis include:

• enlargement of the spleen;
• liver enlargement;
• intense sweating (after chills);
• hypodynamia;
• severe weakness;
• violation of the stool (usually constipation).

The absence of antibiotic therapy leads to multiple violation of the internal organs and death of the patient. With septic shock, thrombosis is possible, combined with hemorrhagic syndrome.

If in septic shock the patient is given adequate antibiotic therapy, then the manifestations of intoxication decrease after 2-4 weeks from the onset of the disease. Against the background of septic shock, due to massive infection and inflammation, arthralgias develop. In severe cases, the patient may develop polyarthritis. In addition, against the background of this condition, the patient may develop symptoms of glomerulonephritis, polyserositis and myocarditis.

Other symptoms that occur with septic shock on the background of various disorders are:

• Symptoms of septic shock in severe DIC and respiratory distress syndrome. In this case, the development of interstitial edema is possible, which entails the appearance of polymorphic shadows and discoid atelectasis in the lungs. Similar changes in the lungs are observed in other severe forms of septic shock. It is noteworthy that on x-ray images, the images of the lungs are almost the same as in pneumonia.
• Septic abortion. As a rule, bleeding does not occur during septic abortion, since in this case an inflammatory reaction is noted in the uterus. As a rule, the vessels are clogged with microbes, blood clots and bloody discharge mixed with purulent masses. Perhaps the development of toxic anemia and a change in skin color. The patient sometimes develops petechial hemorrhages, which can form on the mucous membrane, on the skin and in the internal organs. In some cases, it comes to the formation of extensive superficial necrosis.
• Tachypnea in septic shock. Due to a violation of the activity of the cardiovascular system, a patient with septic shock develops tachypnea. The respiratory rate can reach up to 40 breaths/exhalations per minute.
• Septic pneumonia. This is a fairly common complication of the septic process in the body.
• Liver damage in septic shock. Pathology is accompanied by a noticeable increase in the size of the liver. The liver is painful, and an increase in the level of transaminases and bilirubin is found in the blood. The prothrombin index, total protein and protein fractions decrease. This situation leads to the development of acute liver failure with irreversible changes.
• Kidney damage in septic shock. With a sharp decrease in the volume of circulating blood and a decrease in blood pressure, diuresis also decreases. Urine acquires a low density and markers of the inflammatory process are found in it. In the kidneys, functional and organic lesions are possible, which are irreversible.
• Disturbance of intestinal motility. With septic shock, intestinal paresis and severe disorders of parietal digestion may develop. A putrefactive process starts in the intestines, septic diarrhea and dysbacteriosis appear. Compensating for such violations is quite difficult.
• trophic disorders. Quite early in septic shock, bedsores occur. This occurs due to microcirculation disorders.
• Enlarged spleen.

Patient response to septic shock

Septic shock is a life-threatening condition. The patient should be immediately hospitalized and intensive care should be started. The disease develops quite rapidly, leading to severe complications up to death. Therefore, it is important to deliver the patient to the hospital as soon as possible.

The diagnosis of "septic shock" is made on the basis of the characteristic symptoms that develop during a massive infectious process. The diagnosis is confirmed by a series of laboratory and instrumental studies.

First of all, the treatment of septic shock should be comprehensive and take into account the type of pathogenic flora that caused the pathology. The main therapeutic measure in septic shock is massive antibiotic therapy, anti-inflammatory therapy and immunomodulatory therapy. Hormone therapy is also possible.

• Antibacterial therapy. Massive antibiotic therapy for septic shock should be accompanied by the use of at least two broad-spectrum antibacterial drugs. If the pathogenic pathogen is isolated and its sensitivity is determined, then directed antibiotic therapy is performed against a specific infection. Antibiotics for septic shock are administered parenterally (into a vein, into a muscle, into a regional artery, or by the endolymphatic route).

During antibiotic therapy, blood cultures are regularly performed to identify pathogenic microbes. Antibiotic treatment can take place over a period of several months until cultures are negative and clinicians achieve sustained clinical recovery.

To improve the body's resistance to the patient, a leukocyte suspension, interferon, hyperimmune antistaphylococcal plasma can be introduced. In severe cases, hormonal corticosteroids are used. Correction of immune disorders in septic shock is carried out with the obligatory consultation of an immunologist.

• Surgery. The most important component in the treatment of septic shock is the removal of dead tissue. Depending on the localization of the focus, various surgical interventions are performed.
• Supportive care. To maintain the vital activity of the most important organs and systems, drugs such as dopamine hydrochloride and other drugs that maintain a normal level of blood pressure are used. Oxygen mask inhalations are carried out to ensure proper oxygenation.

Complications of septic shock

With septic shock, the activity of most internal organs and systems is disrupted. This condition is fatal.

Prevention of septic shock

Prevention of septic shock is a measure that prevents the development of blood poisoning. In septic shock, it is important to prevent the development of organ failure and maintain the patient's normal vital functions.

Description:

Septic shock is a complex pathophysiological process resulting from the action of an extreme factor associated with the breakthrough of pathogens and 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. processes.

Symptoms:

Symptoms of septic shock depend on the stage of shock, the microorganism that caused it, and the age of the patient.

Initial stage: decrease in urination, a sudden increase in temperature above 38.3 °, diarrhea and loss of strength.

Late stage: restlessness, feeling irritable, thirst due to reduced blood flow to the brain tissues, rapid heart rate and rapid breathing. In infants and old people, the only signs of shock may be low blood pressure, clouding of consciousness, and rapid breathing.

Low body temperature and decreased urination are common late signs of shock. Complications of septic shock are disseminated intravascular coagulation, renal and peptic ulcers, and liver dysfunction.

Causes of occurrence:

Septic shock (infectious-toxic, bacteriotoxic or endotoxic) develops only with generalized infections that occur with massive bacteremia, intense decay of bacterial cells and the release of endotoxins that disrupt the regulation of the volume of the vascular bed. Septic shock can develop not only with bacterial, but also with viral infections, protozoan invasions, fungal sepsis, severe injuries, and so on.

Treatment:

For treatment appoint:

The first step is to stop the progression of shock. Fluids are usually administered intravenously and pressure in the pulmonary artery is monitored. Infusion of whole blood or plasma can raise the pressure in the pulmonary artery to a satisfactory level. To overcome hypoxia may be required. The introduction of a catheter into the urinary tract allows you to accurately assess the amount of urine separated per hour.

Antibiotics are given immediately (intravenously) to fight the infection. Depending on which microorganism is the causative agent of the infection, complex antibiotic treatment is carried out (usually an aminoglycoside is used in combination with penicillin). If a staphylococcal infection is suspected, a cephalosporin is used. If the infection is caused by non-spore-forming anaerobic organisms, chloromycetin or cleocin is prescribed. However, these drugs can cause unpredictable reactions. All products should only be used as directed by a physician. In the presence of abscesses, they are excised and drained to clear the purulent focus.

If fluids do not relieve shock, dopastat increases blood pressure to maintain blood perfusion in the brain, liver, gastrointestinal tract, kidneys, and skin. Bicarbonate is used as a remedy for acidosis (intravenously). Intravenous corticosteroids may improve blood perfusion and cardiac output.