Sepsis. Treatment

The incidence of sepsis in the United States currently amounts to thousands of cases per year, and mortality reaches thousands (Angus D. C, 2001). According to some data, among patients who have had sepsis, 82% die after 8 years, and the predicted life expectancy is 5 years (Quartin A. A.).

Sepsis is not so much the presence of live bacteria in the patient’s blood (“bacteremia”), but rather the result of a “cascade” of humoral and cellular reactions associated with the release of cytokines from host cells (macrophages, neutrophils) stimulated by bacterial toxins

The release of pro-inflammatory cytokines, tumor necrosis factor, interleukins and other agents (products of complement activation, vasoconstrictors and dilators, endorphins) causes a damaging effect on the vascular endothelium, which is the central link in the spread of systemic inflammation beyond the boundaries of the vascular bed and its adverse effects on target organs.

Toxic bacterial products, entering the circulation, activate systemic defense mechanisms. Subsequently, macrophages begin to secrete anti-inflammatory cytokines IL 10, IL 4, IL 13, soluble TNF receptors and others, aimed at suppressing a generalized infection.

Sepsis is a pathological process that is a phase (stage) of the development of any infectious disease with different primary localization of the lesion, which is based on the formation of a systemic generalized inflammation reaction. Conference of Clinical Chemotherapists and Microbiologists (2001)

Surgical sepsis is a severe general infectious-toxic disease that occurs as a result of a sharp disruption in the relationship between infectious agents and immune defense factors in the primary focus, which leads to the failure of the latter, secondary immunodeficiency and disturbances of homeostasis. (Conference on diagnostic and treatment standards in purulent surgery (2001)

ACCP/SCCM Classification and Terminology of the Society of Thoracic Surgeons and Intensive Care Physicians (R. Bone et al. 1992) Bacteremia the presence of viable bacteria in the blood (Comment: bacteremia is an optional sign and should not be considered as a criterion for sepsis, but as a laboratory phenomenon. Detection of bacteremia should prompt an aggressive search for the source of infection in patients with suspected sepsis (it must be taken into account that instead of bacteremia there may be toxinemia or a mediator).

2. Systemic Inflammatory Response Syndrome (SIRS). This is a pathological condition, which is one of the forms of surgical infection or tissue damage of a non-infectious nature (trauma, burn, ischemia, etc.) and is clinically characterized by the presence of at least two (for CS three) of the following signs:

38.5 °C or 90 beats/min. 3. Respiratory rate > 20 per minute or PaCO2 38.5 °C or 90 beats/min. 3. Respiratory rate > 20 per minute or PaCO2 11 1. Body temperature > 38.5 °C or 90 beats/min. 3. Respiratory rate > 20 per minute or PaCO2 38.5 °C or 90 beats/min. 3. Respiratory rate > 20 per minute or PaCO2 38.5 °C or 90 beats/min. 3. Respiratory rate > 20 per minute or PaCO2 38.5 °C or 90 beats/min. 3. Respiratory rate > 20 per minute or PaCO2 38.5 °C or 90 beats/min. 3. Respiratory rate > 20 per minute or PaCO2 title="1. Body temperature > 38.5 °C or 90 beats/min. 3. Respiration rate > 20 per minute or PaCO2

4. Severe sepsis Sepsis associated with organ dysfunction, hypoperfusion or hypotension. Perfusion disorders may include: lactic acidosis, oliguria, acute impairment of consciousness. Hypotension systolic arterial pressure less than 90 mm Hg. Art. or its decrease by more than 40 mm Hg. Art. from the usual level in the absence of other causes of hypotension.

Clinical and laboratory signs of organ dysfunction (one of the following is sufficient): dysfunction in the homeostasis system (consumption coagulopathy): fibrinogen degradation products > 1/40; dimers > 2; prothrombin index 0.176 µmol/l; sodium in urine 34 µmol/l; increase in AST, ALAT, or alkaline phosphatase levels by 2 times or more from upper limit norms; CNS dysfunction: 1/40; dimers > 2; prothrombin index 1/40; dimers > 2; prothrombin index 0.176 µmol/l; sodium in urine 34 µmol/l; an increase in AST, ALAT, or alkaline phosphatase levels to 2 times or more the upper limit of normal; CNS dysfunction: 1/40; dimers > 2; prothrombin index 1/40; dimers > 2; prothrombin index uk-badge="" uk-margin-small-right="">

The first is a complication of the inflammatory process, interconnected with the state of the primary focus. This type of sepsis is largely considered as a complication and is presented at the end of the diagnosis. For example: open fracture shin bones, extensive anaerobic phlegmon of the shin and thigh, sepsis.

The second clinical variant of sepsis, septicopyemia, is a rare disease or complication when the determining criterion is the occurrence of metastatic foci. When formulating a diagnosis, the word “sepsis” in such cases is brought forward, then the localization of the lesions is indicated.

To standardize the assessment of sepsis and obtain comparable results across studies, the use of severity scoring systems such as SAPS and APACHE is recommended. Diagnosis of organ dysfunction and assessment of its severity should be carried out using the MODS and SOFA scoring scales, which have great information value with a minimum of clinical and laboratory parameters.

85%); - dysfunction of the central nervous system (80%); -leukocytosis (> 85%) and a shift in the blood count to the left (up to 90%); - anemia (80-100%); - hypoproteinemia (80%); - toxic myocarditis" title=" The symptoms of sepsis are characterized by polymorphism. It is manifested by: - ​​fever (>85%); - dysfunction of the central nervous system (80%); - leukocytosis (> 85%) and a shift in the blood count to the left (up to 90%); - anemia (80-100%); - hypoproteinemia (80%); - toxic myocarditis" class="link_thumb"> 28 !} The symptoms of sepsis are polymorphic. It manifests itself: -fever (>85%); - dysfunction of the central nervous system (80%); -leukocytosis (> 85%) and a shift in the blood count to the left (up to 90%); - anemia (80-100%); - hypoproteinemia (80%); - toxic myocarditis (up to 80%); -increased ESR(>85%); - the primary focus is detected in 100% of patients. -Respiratory distress syndrome is detected in 40% of patients, -DIC syndrome in 11% 85%); - dysfunction of the central nervous system (80%); -leukocytosis (> 85%) and a shift in the blood count to the left (up to 90%); - anemia (80-100%); - hypoproteinemia (80%); - toxic myocarditis "> 85%); - dysfunction of the central nervous system (80%); - leukocytosis (> 85%) and shift of the blood count to the left (up to 90%); - anemia (80-100%); - hypoproteinemia (in 80 %)); - toxic myocarditis (up to 80%); - increased ESR (> 85%); - the primary focus is detected in 100% of patients. - Respiratory distress syndrome is detected in 40% of patients, - DIC syndrome in 11%"> 85%); - dysfunction of the central nervous system (80%); -leukocytosis (> 85%) and a shift in the blood count to the left (up to 90%); - anemia (80-100%); - hypoproteinemia (80%); - toxic myocarditis" title=" The symptoms of sepsis are characterized by polymorphism. It is manifested by: - ​​fever (>85%); - dysfunction of the central nervous system (80%); - leukocytosis (> 85%) and a shift in the blood count to the left (up to 90%); - anemia (80-100%); - hypoproteinemia (80%); - toxic myocarditis"> title="The symptoms of sepsis are polymorphic. It manifests itself: -fever (>85%); - dysfunction of the central nervous system (80%); -leukocytosis (> 85%) and a shift in the blood count to the left (up to 90%); - anemia (80-100%); - hypoproteinemia (80%); - toxic myocarditis"> !}

The causative agents of sepsis can be almost all pathogenic and opportunistic bacteria. The most common causative agent of sepsis is the genus Staphylococcus. Mainly, S.aureus (15.1%), E.coli (14.5%), S.epidermidis (10.8%), other coagulase-negative staphylococci (7.0%), S. pneumoniae are cultured from the blood during bacteremia (5.9%), P. aeruginosa (5.3%), K. pneumoniae (5.3%). Low virulent microorganisms are significant as pathogens when isolated from two or more samples of material. In recent years, certain changes have occurred in the etiology of cholesterol towards an increasing role of saprophytic staphylococci, enterococci and fungi.

Septic shock is the result of decompensated multiple organ failure, which develops before the appearance of hemodynamic disturbances as a result of complex metabolic and immunological reactions leading to disruption of transcapillary metabolism.

The most important aspect of sepsis therapy is the sanitation of primary and secondary purulent foci according to the principles of active surgical treatment with the removal of all non-viable tissues, adequate drainage, early closure of wound surfaces using sutures or various types of plastic surgery.

1. Methods whose effectiveness has been confirmed by extensive clinical practice - adequate antibiotic therapy; -respiratory support. (ventilator or oxygen support for spontaneous breathing). -Infusion-transfusion and detoxification therapy. -nutritional support. -hemodialysis for acute renal failure.

3. Methods and drugs, the use of which is pathogenetically justified, but whose effectiveness has not been confirmed from the standpoint of evidence-based medicine: heparin therapy antioxidants protease inhibitors karyoplasm pentoxifylline prolonged hemofiltration corticosteroids monoclonal antibody therapy recombinant antithrombin III albumin

4. Methods widely used in practice, but without substantiated evidence of their effectiveness either experimentally or in the clinic: hemosorption, lymphosorption, indirect electrochemical oxidation of blood with sodium hypochlorite, ultraviolet irradiation, intravenous infusion of blood, lymph, plasma, infusion of ozonated solutions of crystalloids, endolymphatic antibiotic therapy, infusion of xenoperfusate.

Sepsis- a word of Greek origin, meaning decomposition, rotting. Its prevalence in different clinics, and especially in different countries, is different. In Europe and America, it is found in 15-20% of cases and is one of the main causes of deaths in intensive care units, but in Russia it accounts for less than 1% of all surgical diseases.

This difference in morbidity and mortality is explained not by differences in the quality of medical care, but by inconsistency in classifications and definitions.

Etiology

Sepsis can be caused various types bacteria, viruses or fungi. The most common bacterial forms of the disease.

In most large medical centers, the incidence of gram-positive and gram-negative sepsis appears to be approximately the same.

Pathogenesis

The main trigger of sepsis is the interaction of bacteria or bacterial cell fragments with macrophages and neutrophils. Under the influence of excess microbial load, inflammatory mediators - cytokines, which are small protein-peptide information molecules synthesized by hematopoietic cells, are released from them and enter the bloodstream. bone marrow.

According to the mechanism of action, cytokines can be divided into pro-inflammatory, ensuring the mobilization of the inflammatory response (IL-1, IL-6, IL-8, tumor necrosis factor - TNF-a, etc.), and anti-inflammatory, limiting the development of inflammation (IL-4, IL -10, IL-13, soluble receptors for TNF-a, etc.). The pivotal role in the generalization of the inflammatory reaction belongs to the cytokine TNF-a, which can accumulate in the systemic circulation, including with the help of other inflammatory mediators.

The greater the number of bacterial cells and the higher their virulence, the more active the process of cytokine release occurs. They determine the presence and severity of the systemic response to inflammation, causing vasodilation, hypovolemia and tissue ischemia, promoting an increase in body temperature, inflammatory changes in the blood, causing hypercoagulation.

Hypovolemia and tissue ischemia lead to organ hypoperfusion, excessive accumulation of intermediate products of normal metabolism (lactate, urea, creatinine, bilirubin), products of perverse metabolism (aldehydes, ketones) and, ultimately, to multiple organ failure and death.

In pathogenesis septic shock a large role is played by the excessive concentration of nitric oxide, which occurs as a result of stimulation of macrophages by TNF-a and IL-1.

Excessive microbial load also leads to immunological changes. Heat shock proteins are synthesized in ischemic cells, disrupting the function of T-lymphocytes and accelerating their death. The activity of B lymphocytes decreases, which helps to reduce the synthesis of immunoglobulins.

Thus, the main pathogenetic factors in the occurrence of sepsis are a large number of bacteria, their virulence and depletion of the body’s defenses.

Modern classification of sepsis

Currently, sepsis is usually divided according to severity and depending on the entry point of infection.

By severity:

• sepsis is a systemic response to inflammation of infectious origin; most often corresponds to a condition of moderate severity; no hypotension or organ dysfunction;
• severe sepsis or sepsis syndrome - a systemic response to inflammation with dysfunction of at least one organ or hypotension of less than 90 mm Hg. Art.; corresponds to the serious condition of the patient;
• septic shock - sepsis with hypotension that persists despite adequate correction of hypovolemia; corresponds to a state of extreme severity.

Depending on the entrance gate of the infection: surgical, gynecological, urological, odontogenic, tonsillar, wound, etc.

Clinical picture

The pathological processes observed during sepsis affect almost all organs and systems of the body.

Violation of thermoregulation manifests itself in the form of hyperthermia, hectic fever, shaking chills. In the terminal phase, a decrease in body temperature below normal is often observed.

Changes in the central nervous system - disturbances in mental status - manifest themselves in the form of disorientation, drowsiness, confusion, agitation or lethargy. Coma is possible, but not typical.

From the outside of cardio-vascular system Tachycardia, vasodilation in combination with vasoconstriction, a drop in vascular tone, a decrease in blood pressure, myocardial depression and a decrease in cardiac output are observed.

From the respiratory system, shortness of breath, respiratory alkalosis, weakening of the respiratory muscles, diffuse infiltrates in the lungs, and pulmonary edema prevail. In severe sepsis, adult respiratory distress syndrome often develops in the form of interstitial edema of the interalveolar septa, which interferes with gas exchange in the lungs.

Changes in the kidneys manifest themselves in the form of hypoperfusion, damage to the renal tubules, azotemia, and oliguria. Pathological processes in the liver and spleen manifest themselves in the form of jaundice, increased levels of bilirubin and transaminases. Objectively and with instrumental research hepatomegaly and splenomegaly are observed.

The gastrointestinal tract reacts to sepsis with nausea, vomiting, diarrhea, and abdominal pain appears or worsens. In these cases, overdiagnosis of peritonitis is dangerous, since determining whether abdominal symptoms are primary or secondary can be extremely difficult, especially in a patient who has recently undergone surgery on the abdominal organs.

Characteristic changes in the blood: neutrophilic leukocytosis and shift of the leukocyte formula to the left, vacuolization and toxic granularity of neutrophils, thrombocytopenia, eosinopenia, decrease serum iron, hypoproteinemia. Violation of systemic coagulation occurs in the form of activation of the coagulation cascade and inhibition of fibrinolysis, which aggravates microcirculatory disorders and organ hypoperfusion.

Clinical picture sepsis depends on the nature of the microbial flora: gram-positive more often causes disruption of the cardiovascular system, for example infective endocarditis with damage to the heart valves, gram-negative - hectic fever, chills, secondary damage to the gastrointestinal tract.

Metastatic abscesses can occur in almost any part of the body, including brain tissue, meninges, lungs and pleura, and joints. If the abscesses are large, then additional symptoms of damage to the corresponding organ appear.

Septic shock- sepsis with hypotension with systolic blood pressure below 90 mmHg. Art. and organ hypoperfusion despite adequate fluid resuscitation. It occurs in every fourth patient with sepsis, most often caused by gram-negative flora and anaerobic microorganisms (Escherichia coli, Pseudomonas aeruginosa, Proteus, Bacteroides).

In foreign literature, septic shock is defined as a condition in which body tissues receive an inadequate amount of oxygen as a result of hypoperfusion caused by the release of large amounts of toxins and biologically active substances under the influence of infection.

Hypoxia is the most important cause of the development of multiple organ failure. The characteristic clinical picture of shock, as a rule, makes it possible to recognize sepsis without much difficulty.

Diagnosis of sepsis

The diagnosis of sepsis implies the presence of systemic inflammatory response syndrome (SIRS) and an infectious agent (bacterial, viral or fungal) that caused SIRS.

SIRS is diagnosed when two or more of the following 4 signs are present:

• temperature - more than 38° or less than 36°C;
• tachycardia - more than 90 beats per minute;
• respiratory rate - more than 20 per minute;
• the number of blood leukocytes is more than 12-109/l or less than 4-109/l, band forms - more than 10%.

The infectious agent is identified different ways. Laboratory diagnostics is based on identifying markers of systemic inflammation: procalcitonin, C-reactive protein, IL-1, IL-6, IL-8, IL-10, TNF-a.

Procalcitonin is the most effective indicator of sepsis; its properties allow for differential diagnosis of bacterial and non-bacterial inflammation, assessment of the severity of the patient’s condition and the quality of treatment. In healthy people, the level of procalcitonin does not exceed 0.5 ng/ml.

Its values ​​in the range of 0.5-2.0 ng/ml do not exclude sepsis, but may be a consequence of conditions when pro-inflammatory cytokines are released without the presence of an infectious agent: as a result of extensive trauma, major surgery, burns, small cell lung cancer, medullary cancer thyroid gland. If the value is more than 2 ng/ml, sepsis or severe sepsis is highly likely to be diagnosed, and more than 10 ng/ml - severe sepsis or septic shock.

Microbiological diagnostics. A bacteriological examination is carried out not only of blood, but also of material from wounds, drainages, catheters, endotracheal and tracheostomy tubes. The results are compared with each other. Materials are taken before the start antibacterial therapy.

The optimal amount of blood taken during one sample is 10 ml. Blood is taken three times, at the peak of the temperature rise, with an interval of 30-60 minutes, from different veins. If there is an intravenous catheter, blood is taken both from it and by venipuncture for comparative analysis and exclusion of catheter-associated sepsis. The effectiveness of the study of venous and arterial blood is the same.

Using standard commercial culture media bottles is more effective than using tubes sealed with a cotton swab. If microorganisms that are skin saprophytes are isolated, it is recommended to repeat the culture. Only repeated isolation of the same saprophyte should be considered sufficient to make an etiological diagnosis.

The absence of microbial growth does not negate the clinical diagnosis. The presence of microbial growth in the absence of a systemic response to inflammation does not provide grounds for diagnosing sepsis; the case is regarded as bacteremia.

Pathological diagnosis. Cell necrosis, characteristic of organ failure and, consequently, severe sepsis, can be observed in the myocardium, liver, kidneys, and lungs.

In the liver, there is necrosis of hepatocytes, a decrease in the number of endothelial cells and Kupffer cells, in the kidneys there is cortical ischemia with tubular necrosis, in the lungs there is a picture of adult respiratory distress syndrome in the form of interstitial edema, leukocyte infiltration of the walls of the alveoli and expanded intercellular spaces of the vascular endothelium.

The adrenal glands are characterized by necrosis of the cortex and congestion of the medulla, as well as early autolysis in the center of the organ. Compensatory reactions of the body can manifest themselves in the form of bone marrow hyperplasia and an increase in the number of basophils in the anterior pituitary gland.

In the vessels of various organs, small scattered blood clots, focal necrosis and ulcers of the gastrointestinal tract, as well as hemorrhages and bleeding into the serous cavities, characteristic of DIC, are often detected.

The study of tissue microflora is based on the postulate that there is no post-mortem dissemination of microbes: if the corpse is properly stored, they are found only in those places where they were present during life. Tissues of septic lesions, spleen, liver, lungs, kidneys, fragments of intestines, myocardium, etc. are examined.

Pieces of at least 3 × 3 cm are fixed, the prepared paraffin sections are stained with hematoxylin-eosin, and for a more detailed study - with Azur-P-eosin or Gram and processed using the CHIC reaction. Typical sign septic focus - neutrophilic infiltration around accumulations of microorganisms. To accurately determine the type of microorganisms, it is preferable to treat cryostat or paraffin sections with luminescent antimicrobial serums.

A blood test is carried out as follows. Cadaveric blood is taken before opening the skull cavity. After removing the sternum and opening the pericardium from the cavities of the heart, 5 ml of blood is drawn into a sterile syringe for inoculation on nutrient media. Diagnosis is also effective by determining the level of procalcitonin in the blood serum.

Prognostic signs

In order to objectify the assessment of the probability of death in sepsis, the APACHE II (Acute Physiology And Chronic Health Evaluation) scale is the most informative, i.e. scale for assessing acute and chronic functional changes.

There are other scales used in critical conditions both to assess organ failure (for example, the MODS scale) and to predict the risk of death (the SAPS scale, etc.). However, the SAPS score is less informative than the APACHE II score, and the SOFA multiple organ dysfunction score is clinically more meaningful and easier to use than the MODS score.

Treatment

Surgical treatment includes:

• elimination of the source of infection (elimination of defects in hollow organs, closure of defects in integumentary tissue, etc.); if it is impossible to eliminate the source of infection, the source of infection is turned off (proximal stoma, bypass anastomosis) and/or delimited (placement of tampons, drainage foam system);
• sanitation of wounds, necrectomy (use of ozonated solutions and hyperbaric oxygenation - an important component of sanitation of purulent wounds with anaerobic pathogens);
• removal of foreign bodies, implants, infected drains and catheters; in the absence of infection of the surrounding soft tissues, it is possible to replace the infected catheter or drainage along the guide;
• adequate drainage of purulent wounds and cavities;
• dressings.

The choice of antibiotic before obtaining the result of a bacteriological study depends on:

• on the presence and location of the source of infection;
• whether a community-acquired or hospital-acquired infection caused sepsis;
• on the severity of the disease (sepsis, severe sepsis or septic shock);
• from previous antibiotic therapy;
• on individual tolerance to antibacterial drugs.

For antibiotic therapy for sepsis, carbapenems, cephalosporins in combination with aminoglycosides, glycopeptides and fluoroquinolones in combination with lincosamides or metronidazole are of greatest importance.

Carbapenems(ertapenem, imipenem, meropenem) are characterized by the widest spectrum of antimicrobial activity and are used in the most severe cases - sepsis syndrome and septic shock.

Refusal of imipenem is justified only in two cases - with meningitis - due to possible adverse reactions (treatment with meropenem is possible instead) and in the presence of microflora insensitive to carbapenems (for example, methicillin-resistant staphylococcus - MRSA). Ertapenem, which is inactive against Pseudomonas aeruginosa, is more often prescribed for community-acquired infections.

Cephalosporins 3rd and 4th generation are widely used in treatment different types sepsis. Their weak activity against anaerobic microorganisms should be taken into account and combined with metronidazole or lincosamides.

It is advisable to use 3rd generation cephalosporins with aminoglycosides and metronidazole. For sepsis caused by Enterobacteriaceae and Klebsiella, treatment with cefepime (4th generation) is more rational.

Glycopeptides(vancomycin and teicoplanin) are prescribed for sepsis caused by a nosocomial gram-positive infection, such as MRSA. For vancomycin-resistant staphylococcus, rifampicin and linezolid are used.

Linezolid has activity similar to vancomycin against MRSA, E. faecium, clostridial infection, but, compared favorably with vancomycin, it acts on gram-negative anaerobes, in particular bacteroides, fusobacteria. With a large spectrum of gram-negative flora, it is advisable to combine linezolid with 3-4th generation cephalosporins or fluoroquinolones.

Fluoroquinolones highly active against gram-negative flora, but inactive against anaerobes, therefore they are often prescribed in combination with metronidazole. Their combination with linezolid is favorable. In recent years, the 2nd generation of fluoroquinolones with greater activity against gram-positive bacteria (levofloxacin) has been used more often, which allows monotherapy for sepsis.

Polymyxin B active against a wide range of microorganisms, including multiresistant strains. A long-known drug, not previously used due to neuro- and nephrotoxicity, is now recommended as a means of combating hospital-acquired infections resistant to other antibacterial drugs. Toxicity is neutralized when hemoperfusion is performed through columns with polymyxin B.

Caspofungin, fluconazole and amphotericin B (in the original or liposomal form), often prescribed sequentially, are effective in the treatment of fungal forms of sepsis.

Extracorporeal detoxification

Hemofiltration- removal of predominantly medium-molecular substances and liquids from extracorporeally circulating blood through a semi-permeable membrane by filtration and convection transfer.

Large molecules that do not pass through the hemofilter can be absorbed by it, but low-molecular toxins are not excreted in sufficient quantities, which prevents the effective use of hemofiltration in acute renal failure. In addition, the method requires adjustment of doses of antibiotics, since some of them are excreted from the body.

Hemodialysis- a method of removing low molecular weight toxins and liquid through a semi-permeable membrane from extracorporeally circulating blood into the dialysate solution. Used for the development of renal failure.

Hemodiafiltration- a method that is a combination of hemofiltration and hemodialysis. Both filtration of blood with replacement and filtration transfer of toxins through a semi-permeable membrane are used.

Isolated ultrafiltration- removal of excess fluid from the patient’s body as a result of convection through highly permeable membranes. Used for heart failure with pulmonary edema. Expands the capabilities of infusion therapy.

Immunocorrection. The most effective is a preparation of human immunoglobulins enriched with IgM. 1 ml of this drug contains 6 mg IgA, 38 mg IgG and 6 mg IgM.

Infusion therapy- an integral part of the treatment of sepsis. Hypovolemia is corrected with plasma-substituting and water-electrolyte solutions. In case of severe hypovolemia, requiring the administration of more than 3 liters of fluid per day, intra-aortic infusions are advisable.

Transfusion therapy carried out to correct anemia, leukopenia, thrombocytopenia and dysproteinemia with drugs and blood components. The indication for red blood cell transfusion is a decrease in hemoglobin below 70 g/l.

Improving the rheological properties of blood, treatment of DIC syndrome. Heparin is administered in an average of 5 thousand units. three times a day or low molecular weight heparins once a day, antiplatelet agents (Aspirin, Curantil, Trental). Administration of activated protein C (Sigris) at a dose of 24 mcg/kg/h for 96 hours significantly reduces the risk of death (by 19.4%) not only due to inhibition of thrombin production and activation of fibrinolysis, but also due to direct anti-inflammatory and protective effects on endothelial cells.

Inotropic support cardiac activity consists in the timely use of Norepinephrine, Dobutamine, Dopamine in the form of monotherapy or a combination of these drugs.

Oxygen therapy, artificial ventilation lungs (ventilators) are aimed at maintaining an optimal level of blood oxygenation. Indications for respiratory support are ineffective spontaneous breathing, septic shock, and impaired mental status.

Ventilation with a standard tidal volume and high positive end-expiratory pressure may trigger the release of additional cytokines by alveolar macrophages. Therefore, mechanical ventilation with a reduced tidal volume (6 ml per 1 kg of body weight) and positive end-expiratory pressure (10-15 cm of water column) is used.

The preferred mode of assisted breathing. Ventilation of the lungs is periodically undertaken in the prone position, which promotes the involvement of non-functioning alveoli in gas exchange.

Enteral nutrition for sepsis - the preferred method of nutritional support. Food is given in liquid, crushed form; broths and liquid porridges are well digested. It is convenient to use balanced mixtures for enteral nutrition. However, with severe intestinal paresis and in the early postoperative period, it is necessary to resort to parenteral administration of nutrients.

With parenteral nutrition, glucose should cover about 50% of the body's energy needs. In addition, solutions of amino acids and fat emulsions are infused. Convenient drip administration of balanced drugs covering the daily need for nutrients(for example, central cabin).

Drug prevention of stress gastroduodenal ulcers is most effective when prescribing 40 mg of Omeprazole intravenously 2 times a day for 3-7 days. In hyperacid conditions, Sucralfate is indicated - a gastroprotector that polymerizes in an acidic environment to form an adhesive protective substance that covers the ulcer surface for 6 hours.

In case of paresis of the gastrointestinal tract, nasogastric intubation is necessary; untimely removal of stagnant contents from the stomach can provoke gastric bleeding from an acute ulcer or erosion.

There are no uniform recommendations regarding the use of steroid hormones. If the patient does not have adrenal insufficiency, many authors refuse to use them. At the same time, adrenal insufficiency often occurs in severe sepsis and almost always in septic shock. In these cases, the administration of hydrocortisone is preferable.

Prospects

Currently being carried out clinical trials new drugs that inhibit bacterial endotoxin - lipopolysaccharide. Among them, Talactoferin (recombinant lactoferrin), recombinant alkaline phosphatase and new hemofilters for the adsorption of lipopolysaccharide are effective.

Drugs are being developed that correct the cascade of inflammatory reactions, such as CytoFab, which is an antibody to a fragment of tumor necrosis factor, and statins, which suppress specific Toll-like receptors on the surface of monocytes. Experiments have shown that the expression of anti-inflammatory cytokines is reduced by stimulation of estrogen receptors, but clinical studies have not yet been conducted.

Recombinant drugs - antithrombin and thrombomodulin - also still in experiment - are used to correct hypercoagulation and disseminated intravascular coagulation syndrome, which play a significant role in the development of multiple organ failure in sepsis.

The immunomodulatory effect of the combination of Ulinastatin (serine protease inhibitor) and Thymosin alpha-1 continues to be studied, and the possibilities of introduction and differentiation of mesenchymal stem cells are being explored. This may help prevent immunosuppression associated with excessive microbial load.

Lecture 12

The problem of purulent infection, and with it sepsis, is of great current importance. This is due, first of all, to the increase in the number of patients with purulent infection, the frequency of its generalization, as well as the extremely high mortality rate associated with it (up to 35-69%).

The reasons for this situation are well known and many experts associate them with changes in both the reactivity of the macroorganism and the biological properties of microbes under the influence of antibacterial therapy.

According to the literature, a unity of views on critical issues sepsis problems. In particular:

There is disagreement in the terminology and classification of sepsis;

It has not been finally decided what sepsis is - a disease or a complication of a purulent process;

The clinical course of sepsis is classified differently.

All of the above clearly emphasizes that many aspects of the problem of sepsis require further study.

Story. The term "sepsis" was introduced in medical practice in the 4th century AD by Aristotle, who defined the concept of sepsis as poisoning of the body by the products of decay of its own tissue. The development of the doctrine of sepsis throughout the entire period of its formation reflects the latest achievements of medical science.

In 1865, N.I. Pirogov, even before the era of antiseptics, suggested mandatory participation in the development of the septic process of certain active factors, the penetration of which into the body can develop septicemia.

The end of the 19th century was marked by the flourishing of bacteriology, the discovery of pyogenic and putrefactive flora. In the pathogenesis of sepsis, they began to distinguish putrefactive poisoning (sapremia or ichoremia), caused exclusively by chemicals entering the blood from a gangrenous focus, from putrefactive infection caused by chemicals formed in the blood itself from bacteria that entered it and were there. These poisonings were given the name “septicemia,” and if there were also purulent bacteria in the blood, “septicopyemia.”

At the beginning of the twentieth century, the concept of a septic focus was put forward (Schotmuller), who considered the pathogenetic foundations of the doctrine of sepsis from this angle. However, Schottmuller reduced the entire process of development of sepsis to the formation of a primary focus and to the effect of microbes coming from it on a passively existing macroorganism.

In 1928, I.V. Davydovsky developed a macrobiological theory, according to which sepsis was presented as a general infectious disease, determined by a nonspecific reaction of the body to the entry of various microorganisms and their toxins into the bloodstream.

The mid-twentieth century was marked by the development of the bacteriological theory of sepsis, which considered sepsis a “clinical-bacteriological” concept. This theory was supported by N.D. Strazhesko (1947). Adherents of the bacteriological concept considered bacteremia to be either a constant or intermittent specific symptom of sepsis. Followers of the toxic concept, without rejecting the role of microbial invasion, saw, first of all, the cause of the severity of the clinical manifestations of the disease. In poisoning the body with toxins, it was proposed to replace the term “sepsis” with the term “toxic septicemia”.

At the Republican Conference of the Georgian SSR on sepsis, held in Tbilisi in May 1984, an opinion was expressed on the need to create the science of “sepsisology”. At this conference, the definition of the very concept of sepsis caused heated debate. It was proposed to define sepsis as decompensation of the body's lymphoid system (S.P. Gurevich), as a discrepancy between the intensity of toxins entering the body and the detoxifying ability of the body (A.N. Ardamatsky). M.I. Lytkin gave the following definition of sepsis: sepsis is a generalized infection in which, due to a decrease in the anti-infective defense forces, the body loses the ability to suppress the infection outside the primary focus.

Most researchers believe that sepsis is a generalized form of an infectious disease caused by microorganisms and their toxins against a background of severe secondary immunodeficiency. The issues of antibacterial therapy for these patients are considered to be worked out to some extent today, while many criteria for immunocorrection remain unclear.

In our opinion, this pathological process can be given the following definition: sepsis– severe nonspecific inflammatory disease of the entire body, which occurs when a large amount of toxic elements (microbes or their toxins) enter the blood as a result of a sharp violation of its protective forces.

Causative agents of sepsis. The causative agents of sepsis can be almost all existing pathogenic and opportunistic bacteria. Most often, staphylococci, streptococci, Pseudomonas aeruginosa, Proteus bacteria, bacteria of anaerobic flora and bacteroides are involved in the development of sepsis. According to summary statistics, staphylococci are involved in the development of sepsis in 39-45% of all cases of sepsis. This is due to the severity of the pathogenic properties of staphylococci, which is associated with their ability to produce various toxic substances - a complex of hemolysins, leukotoxin, dermonecrotoxin, enterotoxin.

Entrance gate in sepsis, the site of microbial factor introduction into the body tissue is considered. Usually these are damage to the skin or mucous membranes. Once in the tissues of the body, microorganisms cause the development of an inflammatory process in the area of ​​their introduction, which is commonly called primary septic focus. Such primary foci can be various wounds (traumatic, surgical) and local purulent processes of soft tissues (boils, carbuncles, abscesses). Less commonly, the primary focus for the development of sepsis is chronic purulent diseases (thrombophlebitis, osteomyelitis, trophic ulcers) and endogenous infection (tonsillitis, sinusitis, dental granuloma, etc.).

Most often, the primary focus is located at the site of introduction of the microbial factor, but sometimes it can be located far from the site of introduction of the microbes (hematogenous osteomyelitis - a focus in the bone far from the site of introduction of the microbe).

As studies in recent years have shown, when a general inflammatory reaction of the body to a local pathological process occurs, especially when bacteria enter the blood, various areas of necrosis appear in various tissues of the body, which become places where individual microbes and microbial associations settle, which leads to the development secondary purulent foci, i.e. development septic metastases.

This development pathological process for sepsis – primary septic focus – introduction of toxic substances into the blood – sepsis gave rise to the designation of sepsis as secondary diseases, and some experts, based on this, consider sepsis complication main purulent disease.

At the same time, in some patients the septic process develops without an externally visible primary focus, which cannot explain the mechanism of sepsis development. This type of sepsis is called primary or cryptogenic. This type of sepsis is rare in clinical practice.

Since sepsis is more common in diseases that, according to their etiopathogenetic characteristics, belong to the surgical group, the concept has been established in the literature surgical sepsis.

Literature data show that the etiological characteristics of sepsis are supplemented by a number of names. So, due to the fact that sepsis can develop after complications arising after surgical operations, resuscitation aids and diagnostic procedures, it is proposed to call such sepsis nasocomial(acquired within a hospital facility) or Iatrogenic.

Classification of sepsis. Due to the fact that in the development of sepsis main role The microbial factor plays a role; in literature, especially foreign literature, it is customary to distinguish sepsis by the type of microbe that causes it: staphylococcal, streptococcal, colibacillary, pseudomonas, etc. This division of sepsis has important practical significance, because determines the nature of therapy for this process. However, it is not always possible to isolate the pathogen from the blood of a patient with a clinical picture of sepsis, and in some cases it is possible to identify the presence of an association of several microorganisms in the patient’s blood. And finally, the clinical course of sepsis depends not only on the pathogen and its dose, but to a large extent on the nature of the patient’s body’s reaction to this infection (primarily the degree of impairment of his immune forces), as well as on a number of other factors - concomitant diseases, age patient, initial state of the macroorganism. All this allows us to say that it is irrational to classify sepsis only by the type of pathogen.

The classification of sepsis is based on the rate of development factor clinical signs diseases and the severity of their manifestations. According to the type of clinical course of the pathological process, sepsis is usually divided into: fulminant, acute, subacute and chronic.

Since with sepsis two types of pathological process are possible - sepsis without the formation of secondary purulent foci and with the formation of purulent metastases in various organs and tissues of the body, in clinical practice it is customary to take this into account to determine the severity of sepsis. Therefore, sepsis without metastases is distinguished - septicemia, and sepsis with metastases - septicopyemia.

Thus, the classification structure of sepsis can be presented in the following scheme. This classification allows the doctor in each individual case of sepsis to present the etiopathogenesis of the disease and choose the right treatment plan.

Numerous experimental studies and clinical observations have shown that for the development of sepsis the following is of great importance: 1-the state of the nervous system of the patient’s body; 2- the state of its reactivity and 3- anatomical and physiological conditions for the spread of the pathological process.

Thus, it was found that in a number of conditions where there is a weakening of neuroregulatory processes, there is a special predisposition to the development of sepsis. In persons with profound changes in the central nervous system, sepsis develops much more often than in persons without dysfunction of the nervous system.

The development of sepsis is facilitated by a number of factors that reduce the reactivity of the patient’s body. These factors include:

A state of shock that develops as a result of injury and is accompanied by dysfunction of the central nervous system;

Significant blood loss accompanying the injury;

Various infectious diseases that precede the development of an inflammatory process in the patient’s body or injury;

Malnutrition, vitamin deficiency;

Endocrine and metabolic diseases;

Age of the patient (children and elderly people are more easily affected by the septic process and tolerate it less well).

Speaking about the anatomical and physiological conditions that play a role in the development of sepsis, we should point out the following factors:

1 – the size of the primary focus (the larger the primary focus, the greater the likelihood of developing intoxication of the body, introducing infection into the bloodstream, as well as an effect on the central nervous system);

2 – localization of the primary focus (the location of the focus in close proximity to large venous lines contributes to the development of sepsis - soft tissues of the head and neck);

3 – the nature of the blood supply to the area where the primary focus is located (the worse the blood supply to the tissue where the primary focus is located, the more often the possibility of developing sepsis arises);

4 – development of the reticuloendothelial system in organs (organs with developed RES are more quickly freed from infection, and purulent infection develops in them less often).

The presence of these factors in a patient with a purulent disease should alert the doctor to the possibility of sepsis developing in this patient. According to the general opinion, impaired reactivity of the body is the background against which local purulent infection can easily develop into its generalized form - sepsis.

In order to effectively treat a patient with sepsis, it is necessary to have a good knowledge of the changes that occur in his body during this pathological process (diagram).

The main changes in sepsis are associated with:

1- hemodynamic disorders;

2- breathing problems;

3- impaired liver and kidney function;

4- development of physical and chemical changes in the internal environment of the body;

5- disorders in peripheral blood;

6- shifts in the body’s immunological system.

Hemodynamic disorders. Hemodynamic disturbances in sepsis occupy a central place. The first clinical signs of sepsis are associated with disruption of the cardiovascular system. The degree of severity and severity of these disorders are determined by bacterial intoxication, the depth of metabolic processes, the degree of hypovolemia, and the body’s compensatory and adaptive reactions.

The mechanisms of bacterial intoxication in sepsis are combined into the concept of “small output syndrome,” which is characterized by a rapid decrease in cardiac output and volumetric blood flow in the patient’s body, a frequent small pulse, pallor and marbled skin tone, and a decrease in blood pressure. The reason for this is a decrease in the contractile function of the myocardium, a decrease in circulating blood volume (CBV) and a decrease in vascular tone. Circulatory disorders during general purulent intoxication of the body can develop so quickly that clinically this is expressed as a kind of shock reaction—“toxic-infectious shock.”

The appearance of vascular unresponsiveness is also facilitated by the loss of neurohumoral control associated with the influence of microbes and microbial decay products on the central nervous system and peripheral regulatory mechanisms.

Hemodynamic disorders ( low cardiac output, stasis in the microcirculation system) against the background of cellular hypoxia and metabolic disorders, leads to an increase in blood viscosity, primary thrombus formation, which in turn causes the development of microcirculatory disorders - DIC syndrome, which are most pronounced in the lungs and kidneys. A picture of a “shock lung” and a “shock kidney” develops.

Breathing problems. Progressive respiratory failure, up to the development of “shock lung,” is characteristic of all clinical forms of sepsis. The most pronounced signs of respiratory failure are shortness of breath with rapid breathing and cyanosis of the skin. They are caused primarily by disorders of the respiratory mechanism.

Most often, the development of respiratory failure in sepsis is caused by pneumonia, which occurs in 96% of patients, as well as the development of diffuse intravascular coagulation with platelet aggregation and the formation of blood clots in the pulmonary capillaries (DIC syndrome). A more rare cause of respiratory failure is the development of pulmonary edema due to a significant decrease in oncotic pressure in the bloodstream with severe hypoproteinemia.

To this it should be added that respiratory failure can develop due to the formation of secondary abscesses in the lungs in cases where sepsis occurs in the form of septicopyemia.

Impaired external respiration causes changes in the gas composition of the blood during sepsis - arterial hypoxia develops and pCO 2 decreases.

Changes in the liver and kidneys in sepsis they are pronounced and are classified as toxic-infectious hepatitis and nephritis.

Toxic-infectious hepatitis occurs in 50-60% of cases of sepsis and is clinically manifested by the development of jaundice. Mortality in sepsis complicated by the development of jaundice reaches 47.6%. Liver damage in sepsis is explained by the effect of toxins on the liver parenchyma, as well as impaired liver perfusion.

Renal dysfunction is of great importance for the pathogenesis and clinical manifestations of sepsis. Toxic nephritis occurs in 72% of patients with sepsis. In addition to the inflammatory process that develops in the kidney tissue during sepsis, the dysfunction of the kidneys is caused by the DIC syndrome developing in them, as well as vasodilation in the juxtomedullary zone, which reduces the rate of urine excretion in the glomerulus.

Dysfunction vital organs and systems of the patient’s body with sepsis and the resulting disturbances in metabolic processes in it lead to the appearance physico-chemical changes in the internal environment of the patient's body.

In this case the following occurs:

a) Change in acid-base state (ALS) towards both acidosis and alkalosis.

b) Development of severe hypoproteinemia, leading to dysfunction of the plasma buffer capacity.

c) Developing liver failure aggravates the development of hypoproteinemia, causing hyperbilirubinemia, a disorder of carbohydrate metabolism, manifested in hyperglycemia. Hypoproteinemia causes a decrease in the level of prothrombin and fibrinogen, which is manifested by the development of coagulopathic syndrome (DIC syndrome).

d) Impaired renal function contributes to the impairment of acid-base balance and affects water-electrolyte metabolism. Potassium-sodium metabolism is especially affected.

Peripheral blood disorders are considered an objective diagnostic criterion for sepsis. In this case, characteristic changes are found in the formula of both red and white blood.

Patients with sepsis have severe anemia. The reason for the decrease in the number of red blood cells in the blood of patients with sepsis is both the direct breakdown (hemolysis) of red blood cells under the influence of toxins, and the inhibition of erythropoiesis as a result of the effects of toxins on the hematopoietic organs (bone marrow).

Characteristic changes in sepsis are noted in the white blood formula of patients. These include: leukocytosis with a neutrophilic shift, a sharp “rejuvenation” of the leukocyte formula and toxic granularity of leukocytes. It is known that the higher the leukocytosis, the more pronounced the activity of the body’s response to infection. Pronounced changes in the leukocyte formula also have a certain prognostic significance - the lower the leukocytosis, the more likely an unfavorable outcome in sepsis.

When considering changes in peripheral blood during sepsis, it is necessary to focus on disseminated intravascular coagulation (DIC). It is based on intravascular blood coagulation, leading to blockade of microcirculation in the vessels of the organ, thrombotic processes and hemorrhages, tissue hypoxia and acidosis.

The trigger mechanism for the development of DIC syndrome in sepsis is exogenous (bacterial toxins) and endogenous (tissue thromboblasts, tissue decay products, etc.) factors. A large role is also played by the activation of tissue and plasma enzyme systems.

In the development of DIC syndrome, two phases are distinguished, each of which has its own clinical and laboratory picture.

First phase characterized by intravascular coagulation and aggregation of its formed elements (hypercoagulation, activation of plasma enzyme systems and blockade of the microvasculature). When examining blood, a shortening of the clotting time is noted, plasma tolerance to heparin and the prothrombin index increase, and the concentration of fibrinogen increases.

In second phase coagulation mechanisms are depleted. The blood during this period contains a large number of fibrinolysis activators, but not due to the appearance of anticoagulants in the blood, but due to the depletion of anticoagulant mechanisms. Clinically, this is manifested by distinct hypocoagulation, up to complete blood incoagulation, a decrease in the amount of fibrinogen and the value of the prothrombin index. There is destruction of platelets and red blood cells.

Immune shifts. Considering sepsis as the result of a complex relationship between macro- and microorganism, it is necessary to emphasize that the leading role in the genesis and generalization of infection is given to the state of the body's defenses. Of the various mechanisms of the body's defense against infection important role belongs to the immune system.

As numerous studies show, the acute septic process develops against the background of significant quantitative and qualitative changes in various parts of the immune system. This fact requires targeted immunotherapy in the treatment of sepsis.

In recent publications, information has appeared about fluctuations in the level of nonspecific resistance and selective susceptibility to some infectious diseases persons with certain blood groups according to the ABO system. According to the literature, sepsis most often develops in people with blood groups A(II) and AB(IV) and less often in people with blood groups O(1) and B(III). It is noted that people with blood groups A(II) and AB(IV) have low bactericidal activity of blood serum.

The identified correlative relationship suggests a clinical dependence of determining the blood group of people in order to predict their susceptibility to the development of infection and the severity of its course.

Clinic and diagnosis of sepsis. The diagnosis of surgical sepsis should be based on the following points: the presence of a septic focus, clinical picture and blood culture.

As a rule, sepsis without a primary focus is extremely rare. Therefore, the presence of any inflammatory process in the body with a certain clinical picture should force the doctor to assume the possibility of sepsis developing in the patient.

Acute sepsis is characterized by the following clinical manifestations: high body temperature (up to 40-41 0 C) with slight fluctuations; increased heart rate and breathing; severe chills, preceding an increase in body temperature; increase in the size of the liver and spleen; often the appearance of icteric discoloration of the skin and sclera and anemia. The initially occurring leukocytosis may later be replaced by a decrease in the number of leukocytes in the blood. Blood cultures reveal bacterial cells.

The detection of metastatic pyemic foci in a patient clearly indicates the transition of the septicemia phase to the septicopyemia phase.

One of common symptoms in sepsis is heat the patient’s body, which is of three types: wavy, remitting and continuously high. The temperature curve usually reflects the type of sepsis. The absence of a pronounced temperature reaction in sepsis is extremely rare.

Continuously high temperature characteristic of a severe course of the septic process, occurs as it progresses, with fulminant sepsis, septic shock or extremely severe acute sepsis.

Remitting type temperature curve is observed in sepsis with purulent metastases. The patient’s body temperature decreases when the infection is suppressed and the purulent focus is eliminated and increases when it forms.

Wave type temperature curve occurs in subacute sepsis, when it is not possible to control infectious process and radically remove purulent foci.

Speaking about such a symptom of sepsis as high temperature, it should be borne in mind that this symptom is also characteristic of general purulent intoxication, which accompanies any local inflammatory process that occurs quite actively with a weak protective reaction of the patient’s body. This was discussed in detail in the previous lecture.

In this lecture, it is necessary to dwell on the following question: when does the state of intoxication turn into a septic state in a patient with a purulent inflammatory process, accompanied by a general reaction of the body?

The concept of I.V. Davydovsky (1944,1956) about purulent-resorptive fever as a normal general reaction of a “normal organism” to the focus of a local purulent infection, while in sepsis this reaction is caused by a change in the patient’s reactivity to a purulent infection.

Purulent-resorptive fever is understood as a syndrome that occurs as a result of the resorption of tissue decay products from a purulent focus (purulent wound, purulent inflammatory focus), resulting in general phenomena (temperature above 38 0 C, chills, signs of general intoxication, etc.). At the same time, purulent-resorptive fever is characterized by complete compliance with the general phenomena of severity pathological changes at a local outbreak. The more pronounced the latter, the more active the manifestation of general signs of inflammation. Purulent-resorptive fever usually occurs without deterioration general condition, if there is no increase in the inflammatory process in the local focus area. In the coming days after radical surgical treatment of the source of local infection (usually up to 7 days), if foci of necrosis are removed, leaks and pockets with pus are opened, the general symptoms of inflammation sharply decrease or disappear completely.

In cases where, after radical surgery and antibacterial therapy, the symptoms of purulent-resorptive fever do not go away within the specified period, and tachycardia persists, one must think about the initial phase of sepsis. Blood cultures will confirm this assumption.

If, despite intensive general and local therapy for a purulent inflammatory process, high fever, tachycardia, the general serious condition of the patient and intoxication symptoms persist for more than 15-20 days, you should think about transitioning the initial phase of sepsis to the stage active process– septicemia.

Thus, purulent-resorptive fever is an intermediate process between local purulent infection with the general reaction of the patient’s body to it and sepsis.

When describing the symptoms of sepsis, you should dwell in more detail on symptom of the appearance of secondary, metastatic purulent foci, which definitively confirms the diagnosis of sepsis, even if bacteria cannot be detected in the patient’s blood.

The nature of purulent metastases and their localization largely influence the clinical picture of the disease. At the same time, the localization of purulent metastases in the patient’s body depends to a certain extent on the type of pathogen. So, if Staphylococcus aureus can metastasize from the primary focus to the skin, brain, kidneys, endocardium, bones, liver, testicles, then enterococci and viridans streptococci - only to the endocardium.

Metastatic ulcers are diagnosed based on the clinical picture of the disease, laboratory data and the results of special research methods. Purulent foci in soft tissues are recognized relatively easily. To identify ulcers in the lungs and abdominal cavity, X-ray and ultrasound methods are widely used.

Blood cultures. Cultivation of the causative agent of purulent infection from the patient’s blood is the most important point in the verification of sepsis. The percentage of microbes inoculated from the blood, according to various authors, ranges from 22.5% to 87.5%.

Complications of sepsis. Surgical sepsis occurs in an extremely diverse manner and the pathological process in it affects almost all organs and systems of the patient’s body. Damage to the heart, lungs, liver, kidneys and other organs is so common that it is considered sepsis syndrome. The development of respiratory, hepatic-renal failure is more likely the logical end of a serious illness than a complication. However, with sepsis there may be complications, which most experts include septic shock, toxic cachexia, erosive bleeding and bleeding that occurs during the development of the second phase of disseminated intravascular coagulation syndrome.

Septic shock– the most severe and dangerous complication of sepsis, the mortality rate of which reaches 60-80% of cases. It can develop in any phase of sepsis and its occurrence depends on: a) intensification of the purulent inflammatory process in the primary focus; b) the addition of another flora of microorganisms to the primary infection; c) the occurrence of another inflammatory process in the patient’s body (exacerbation of a chronic one).

The clinical picture of septic shock is quite clear. It is characterized by the suddenness of the onset of clinical signs and the extreme degree of their severity. Summarizing the literature data, we can identify the following symptoms that allow us to suspect the development of septic shock in a patient: 1- sudden sharp deterioration in the general condition of the patient; 2 – decrease in blood pressure below 80 mm Hg; 3 – the appearance of severe shortness of breath, hyperventilation, respiratory alkalosis and hypoxia; 4 – sharp decrease in diuresis (below 500 ml of urine per day); 5 – appearance in the patient neuropsychiatric disorders– apathy, adynamia, agitation or mental disorders; 6 – occurrence allergic reactions– erythematous rash, petechiae, peeling of the skin; 7 – development of dyspeptic disorders – nausea, vomiting, diarrhea.

Another serious complication of sepsis is "wound exhaustion", described by N.I. Pirogov as "traumatic exhaustion." This complication is based on a long-term purulent-necrotic process during sepsis, from which the absorption of tissue decay products and microbial toxins continues. In this case, as a result of tissue breakdown and suppuration, protein loss occurs in the tissues.

Erosive bleeding occurs, as a rule, in a septic focus in which the vessel wall is destroyed.

The appearance of one or another complication in sepsis indicates either inadequate treatment of the pathological process, or a sharp violation of the body's defenses with a high virulence of the microbial factor and suggests an unfavorable outcome of the disease.

Treatment of surgical sepsis – represents one of the difficult problems of surgery, and its results have so far been of little satisfaction to surgeons. The mortality rate for sepsis is 35-69%.

Considering the complexity and variety of pathophysiological disorders occurring in the patient’s body during sepsis, treatment of this pathological process should be carried out comprehensively, taking into account the etiology and pathogenesis of the disease. This set of measures must necessarily consist of two points: local treatment primary focus, based mainly on surgical treatment, and general treatment , aimed at normalizing the function of vital organs and systems of the body, fighting infection, restoring homeostasis systems, increasing immune processes in the body (table).

The content of the article

Sepsis(blood poisoning) is a general nonspecific purulent infection caused by various pathogens, in particular microorganisms present in the primary local purulent focus. Sepsis has typical clinical manifestations, independent of the type of pathogen, a severe course, and is characterized by a predominance of intoxication manifestations over local anatomical and morphological changes and high mortality. The modern understanding of sepsis is largely based on the definitions of this pathology and related conditions agreed upon by the Chicago Consensus of Experts (1991, USA) and recommended by the II Congress of Surgeons of Ukraine (1998, Donetsk) for practical use in public health care.

Definitions of sepsis and related conditions (Chicago Consensus of Experts, 1991, USA):

Infection- a phenomenon characteristic of humans, consisting in the body’s inflammatory response to the invasion of microorganisms into its tissues, which are normally sterile.
Bacteremia- the presence of visualized (detectable visually under a microscope) bacteria in the blood.
Systemic inflammatory response syndrome (SIRS)- a systemic inflammatory response of the body to various traumatic factors, the manifestation of which occurs in at least two of the following ways:
- body temperature rises to more than 38 °C or decreases below 36 °C;
- tachycardia is more than 90 beats per minute;
- the respiratory rate is more than 20 per 1 minute, or PCo2 32 - the number of leukocytes in the blood is more than 12,109/l or less than 4,109/l, or more than 10% of their immature forms in the leukocyte formula of the blood.
Sepsis- SIRS, caused by the emergence of a focus of infection in the body.
Severe sepsis- sepsis, accompanied by organ dysfunction, hypoperfusion and arterial hypotension. Hypoperfusion and perfusion disorders may be accompanied by (but are not limited to) lactic acidosis, oliguria, or acute disorders functions of the central nervous system.
Septic shock- sepsis, accompanied by arterial hypotension, which is not eliminated even by intensive adequate infusion therapy, and perfusion disorders that are not limited to lactic acidosis, oliguria or acute disorders of the functions of the central nervous system. In patients receiving inotropic or vasopressor drugs, hypotension may be absent despite the presence of perfusion disorders.
Hypotension(arterial hypotension) is a circulatory condition in which systolic blood pressure is 90 mm Hg. Art. or it decreases by 40 mmHg. Art. from the basic level (in the absence of other obvious reasons for hypotension).
Multiple organ dysfunction syndrome (MODS)- disorders of organ function in patients with acute diseases that make it impossible to maintain homeostasis without medical intervention.
The exact statistics of sepsis cases in Ukraine are unknown. In the USA, 300-400 thousand cases of this disease are registered every year. Septic shock remains the most common cause death of patients in intensive care units, it develops in 40% of patients. Despite intensive treatment, mortality in sepsis reaches 50-60%, since sepsis develops as a result of the interaction of three main factors - the microorganism, as well as the local and systemic protective mechanisms of the macroorganism. The main factors associated with the increased incidence of this disease are:
- inappropriate early treatment of wounds - potential entry points for infection and not adequate treatment purulent surgical infection (boils, abscesses, felon, etc.) and acute or surgical pathology (appendicitis, cholecystitis, pancreatitis, etc.);
- the use of increasingly intense oncological chemotherapy, hormonal and radiation therapy, which weakens the immune system;
- the use of corticosteroids and immunosuppressive therapy in organ transplantation and the treatment of inflammatory diseases;
- increasing the survival rate of patients with defects in immune defense, namely: problematic newborns, the elderly and old age, diabetic and cancer patients, recipients of donor organs, patients with MODS or granulocytopenia;
- intensive use of invasive medical products- prostheses, inhalation devices, intravascular and urological catheters;
- often uncontrolled use of antibiotics by outpatients, which creates favorable conditions for the emergence and development of aggressive antibiotic-resistant flora in their bodies (through both modifications and mutations).
Does not have sepsis incubation period, but necessarily has an entrance gate for infection, which is damage to the skin and mucous membranes through which it penetrates into the body, and a primary focus (a site of inflammation resulting from penetration of infection into the tissue - abscesses, phlegmons, boils, acute surgical pathology) . The presence of sepsis can be confirmed if, having overcome the humoral and cellular defense mechanisms of the macroorganism, a large number of highly virulent pathogens multiply in tissues and constantly release new bacteria and toxins into the bloodstream (causing septicemia) or, using the blood circulation as transport, form new purulent foci in other organs (causing metastatic infection - septicopyemia).
In both cases, the severity of the clinical course of the disease is due to toxemia, i.e., the presence of bacterial toxins in the patient’s blood.
Despite the fact that any type of microorganism can cause the development of septic syndrome or septic shock, most often this pathology is caused by gram-negative bacteria. In intensive care unit patients, the triad of main septic factors is represented by Pseudomonas aeruginosa, Staphylococcus aureus and coagulase-negative staphylococci. Escherichia coli is most often cultured from the urinary canal of these patients. Modern researchers also point to an increase in cases of sepsis caused by gram-positive, predominantly staphylococcal, flora. Anaerobic infections are less likely to cause sepsis. Anaerobic sepsis occurs, as a rule, in individuals with severe damage to the body due to the presence of intra-abdominal or pelvic infectious foci.

Pathogenesis of sepsis

The pathogenesis of sepsis is extremely complex. Sepsis develops as a natural continuation of an infection contained in a local focus in which microorganisms continue to multiply. The main initiator of sepsis is the production or release by bacteria of endotoxin or other products of bacterial origin that cause inflammation. Endotoxin acts on its own cells human body(leukocytes, platelets, endothelial cells), which begin to actively produce inflammatory mediators and products of nonspecific and specific components of immune defense. As a result, a systemic inflammatory response syndrome occurs, the symptoms of which are hypo- or hyperthermia, tachycardia, tachypnea, leukocytosis or leukopenia. Since the main target of these mediators is the vascular endothelium, direct or indirect damage to it, vascular spasm or paresis, or a decrease in the intensity of blood flow leads to the development of the syndrome of increased capillary permeability, manifested in impaired blood microcirculation in all important systems and organs, progression of hypotension, the occurrence of hypoperfusion or dysfunction of individual or several body systems important for life. Disturbance and insufficiency of microcirculation are a natural pathogenetic ending of sepsis, leading to the development or progression of multiple organ failure syndrome, and often to the death of the patient. Most researchers believe that delayed or inadequate treatment of sepsis leads to the fact that these mechanisms begin to progress regardless of the state of the primary source of inflammation and the production of endotoxin by pathogenic microorganisms.

Classification of sepsis

The classification of sepsis is based on its etiology (bacterial gram-positive, bacterial gram-negative, bacterial anaerobic, fungal), the presence of a focus of infection (primary cryptogenic, in which the focus cannot be detected, and secondary, in which the primary focus is detected), the localization of this focus (surgical, obstetric- gynecological, urological, otogenic, etc.), the reason for its occurrence (wound, postoperative, postpartum, etc.), time of appearance (early - develops within 2 weeks from the moment of occurrence of the lesion, late - develops after 2 weeks from the moment occurrence of a focus), clinical course (fulminant, acute, subacute, chronic, septic shock) and form (toxemia, septicemia, septicopyemia).

Sepsis clinic

The clinical picture of sepsis is extremely diverse; it depends on the form of the disease and its clinical course, the etiology and virulence of its causative agent. Classic signs of acute sepsis are hyper- or hypothermia, tachycardia, tachypnea, deterioration of the patient’s general condition, dysfunction of the central nervous system (excitement or inhibition), hepatosplenomegaly, sometimes jaundice, nausea, vomiting, diarrhea, anemia, leukocytosis or leukopenia and thrombocytopenia. The detection of metastatic foci of infection indicates the transition of sepsis to the septicopyemia phase. Fever is the most common, sometimes the only, manifestation of sepsis. Hypothermia may be an early sign of sepsis in some patients, such as those who are malnourished or immunosuppressed, drug addicts, alcohol abusers, diabetics, and those using corticosteroids. Therefore, it must be remembered that neither low nor normal body temperature can be a basis for excluding the diagnosis of sepsis and septic shock.
At the same time, patients with sepsis experience a number of clinical manifestations caused by disorders of blood microcirculation and the functions of vital systems and organs, in particular cardiovascular (hypotension, decreased circulating blood volume, tachycardia, cardiomyopathy, toxic myocarditis, acute cardiovascular failure ), respiratory (tachypnea, hyperventilation, respiratory distress syndrome, pneumonia, lung abscess), liver (hepatomegaly, toxic hepatitis, jaundice), urinary (azotemia, oliguria, toxic nephritis, acute renal failure) and central nervous system (headache, irritability, encephalopathy, coma, delirium).
Laboratory tests can reveal in patients with sepsis numerous hematological (neutrophilic leukocytosis, shift of the leukocyte formula to the left, leukopenia, vacuolization or toxic granularity of leukocytes, anemia, thrombocytopenia) and biochemical (bilirubinemia, azotemia, hypoproteinemia, dysproteinemia, increased blood levels of ALAT, ASAT and alkaline phosphatase, decrease in free iron content, etc.) changes. It is also possible to identify signs of the development of disseminated intravascular coagulation syndrome and acid-base disorders (metabolic acidosis, respiratory alkalosis). During bacteriological examination (culture) of blood, pathogenic bacteria are found in it.
The only condition for the survival of a patient with sepsis is early adequate treatment.

Diagnosis of sepsis

The main task of physicians is constant vigilance against sepsis and its early diagnosis. The main directions of diagnosing sepsis:
1. Identification of at least two of the classical four criteria for SIRS in the patient (hypo- or hyperthermia; tachycardia; tachypnea; leukopenia, leukocytosis or shift of the leukocyte formula to the left).
2. Identification of the patient’s primary source of infection (purulent wound, boil, phlegmon, abscess, etc.).
Identification of SIRS criteria and the primary source of infection in a patient gives reason to suspect sepsis, and therefore, urgently hospitalize him in the surgical department and begin intensive treatment.
The absence of clinical criteria for SIRS in a patient with an inflammatory or purulent disease indicates its controlled course and that the infection will not generalize.
It is most difficult to diagnose sepsis in cases where a surgical patient (with surgical diseases or after operations) shows signs of SIRS, but there are no signs of a focus of infection.
In this case, diagnosis must be comprehensive and urgent. Comprehensiveness should mean the use of the widest range of studies to determine the localization of the primary source of infection - both instrumental (radiography, computed tomography and magnetic resonance imaging, echocardiography, ultrasound) and invasive (puncture of suspicious areas of the body and cavities, vaginal and rectal examinations , laparoscopy, endoscopy, diagnostic operations). Urgency means completing these studies as quickly as possible. Laboratory and functional studies for the diagnosis of sepsis have no independent significance, however, they make it possible to determine the degree of damage to systems and organs, the depth of intoxication and a number of parameters necessary for choosing the appropriate treatment. Bacteriological research blood makes it possible to identify the causative agent of sepsis in approximately 60% of patients. Material for sowing must be taken at different times of the day, preferably at the peak of fever. For bacteriological diagnosis, blood should be collected three times. At the same time, it should be remembered that the absence of pathogenic bacteria in the blood does not exclude the development of sepsis - the so-called sepsis without bacteremia according to Nystrom (Nystrom, 1998).
The basis for starting full treatment of sepsis is the identification of two of its four signs. Further, more in-depth examination of the patient should be carried out during his intensive treatment.

Treatment of sepsis

Treatment of sepsis should be carried out only in a surgical hospital. It should be carried out in parallel in two directions:
- treatment of sepsis itself, which involves both surgical treatment of primary local foci of infection and drug treatment of generalized infection with the help of antibiotics and immunostimulants;
- elimination of symptoms and syndromes that occur during sepsis (hypo- and hyperthermia, cardiovascular and respiratory failure, dysfunction of the central nervous system, etc.).

Treatment of patients with sepsis

Standard therapy:
Antibacterial therapy aimed at destroying sepsis pathogens
(mono-, double or triple antibiotic therapy).
Immunotherapy (administration of specific antibacterial serums and immunostimulants to the patient).
Surgery:
opening and drainage of abscesses;
removal of infected implants, prostheses and catheters;
necrectomy.
Treatment for shock and organ failure:
elimination of cardiovascular and metabolic disorders;
corresponding in volume and composition infusion therapy(introduction saline solutions, blood substitutes, blood transfusion);
administration of cardiovascular and anti-inflammatory drugs, antiplatelet agents, vitamins and antioxidants);
oxygen therapy (hyperbaric oxygenation);
detoxification (hemosorption, hemodialysis, plasmapheresis, enterosorption).
Drugs used to treat sepsis:
Pathogen-specific:
antiendotoxin;
polyclonal antiendotoxic serum;
anti-Gram-positive cell wall substance;
antifungal cell wall substance.
Pathogen-specific antibiotics:
Specific to mediators:
antimediators (antihistamines and antiserotonin drugs, anti-TNF, anti-IL-l, anti-PAF);
monoclonal antibodies;
receptor antagonists.
Preparations of polyvalent antiseptic action:
ibuprofen;
pentoxifylline;
acetylcysteine ​​(ACC);
lactoferrin;
polymyxin B.
Despite significant progress in the treatment of sepsis, patients with sepsis, septic shock and multiple organ failure continue to be a clinical group with extremely high mortality rates. Rapid detection of SIRS and the use of early intensive complex therapy reduces mortality in sepsis by approximately 25%. Further improvement in the results of treatment of patients with sepsis is associated mainly with the development of new effective medicines, allowing to block the negative effect of the main pathogenetic factors of sepsis - toxins and inflammatory mediators.

On average, sepsis develops in 1-13 per 1000 hospitalized patients. In intensive care units it can reach from 3-5.5 to 17%.

Definition pathological conditions associated with sepsis.

Bacteremia is the presence of viable bacteria in the blood (microbiological phenomenon).

Systemic inflammatory response syndrome is a systemic inflammatory response to various severe tissue injuries, manifested by two or more of the following symptoms:

Temperature more than 38.5 o C or less than 36.5 o C;

Tachycardia more than 90 bpm.

Respiration rate is more than 20 per minute. or PaCO 2 less than 32 mmHg.

The number of leukocytes is more than 12,000 per 1 mm 3, less than 4,000. Or more than 10% of band neutrophils.

Sepsis is a systemic inflammatory response to infection (SVR syndrome in the presence of a focus of infection).

Severe sepsis is sepsis associated with organ dysfunction, hypoperfusion, or hypotension. Impaired perfusion may include lactic acidosis, oliguria, acute impairment of consciousness, etc.

Hypotension is a systolic blood pressure less than 90 or a decrease of more than 40 from the usual level in the absence of other causes of hypotension.

Septic shock is sepsis with hypotension that persists despite adequate correction of hypovolemia + perfusion disturbances (lactic acidosis, oliguria or acute impairment of consciousness), requiring the use of catecholamines.

Multiple organ dysfunction syndrome is a dysfunction of organs in a patient in serious condition (it is impossible to maintain homeostasis on its own, without treatment).

Primary sepsis (cryptogenic)

Secondary sepsis develops against the background of a purulent focus)

By localization primary focus: surgical (acute and chronic surgical diseases, injuries, diagnostic procedures, complications surgical interventions), gynecological, urological, otogenic, odontogenic, nosocomial (heart valves, vascular prostheses, joints, catheters in blood vessels, etc.)

By type of pathogen: staphylococcal, streptococcal, colibacillary, anaerobic. Gram-positive, gram-negative.

The entrance gate is the site of infection (usually damaged tissue).

The primary focus is an area of ​​inflammation that arises at the site of infection and subsequently serves as a source of sepsis. In some cases, the primary focus may not coincide with the entrance gate due to lymphadenitis.

Secondary foci - the spread of infection beyond the primary focus with the formation of pyemic foci in organs and tissues. Previously, Cruvelier’s embolic theory. Now - hyperfermentemia - impaired capillary circulation - migration of leukocytes with the release of toxic proteins - necrosis - infection.

Pathogens

Previously, in the 30-50 years - mainly streptococcus, then staphylococcus and gram-negative microflora. More often, sepsis is caused by monoculture (about 90%), while an association of microbes can be seeded in the primary focus.

Based on the microflora of the primary focus, it is not always possible to judge the nature of the causative agent of sepsis (for example, in the primary focus there is a gram-negative flora, in the blood it is gram-positive).

The clinical picture is largely determined by the properties of the pathogen.

Staphylococcus has the ability to coagulate fibrin and settle in tissues - in 95% of cases it quickly leads to the formation of pyemic lesions.

Streptococcus has pronounced fibrinolytic properties - it rarely causes pyemia (35%).

E. coli – mainly has a toxic effect.

A stick of blue-green pus - metastatic foci are few, small, often localized under the epicardium, pleura, kidney capsule, while in staphylococcal sepsis the foci are large and localized in soft tissues, lungs, kidneys, bone marrow.

Due to the pronounced intoxicating effect, gram-negative flora leads to the development of septic shock in 2/3 of cases.

In most cases, blood is not a breeding ground for microbes.

In addition to the characteristics of microbes, the course of sepsis is greatly influenced by the number of microbial bodies themselves - over 10 in 5.

Symptoms of surgical sepsis.

Primary focus – 100%

Intoxication – 100%

Positive repeat blood cultures – 80%

Temperature above 38 - 90% - three types: continuous, remitting, wave-like

Tachycardia – 80%

Toxic myocarditis, toxic hepatitis, nephritis, chills, peripheral edema.

Diagnostics.

The basis of diagnosis is the clinical picture.

Search for pyemic foci.

Important is the microbiological (qualitative and quantitative) examination of blood discharged from wounds or fistulas, tissue of a purulent focus, as well as (depending on the possible localization of foci of inflammation) urine, cerebrospinal fluid, sputum, pleural and abdominal exudate, etc.

An objective assessment of the severity of the patient’s condition upon admission and during intensive care should be carried out on the basis of the integrated systems SAPS, APACHE, SOFA.

Examination and treatment of a patient with surgical sepsis should be carried out in an intensive care unit together by a surgeon and a resuscitator.

Surgery.

Surgical treatment of primary and secondary purulent foci.

Complete excision of non-viable tissue;

Complete flow drainage;

Washing the lesions with antiseptics;

It is possible to close the wound earlier with sutures or using skin grafting - 1500 ml of water evaporates from a wound with an area of ​​10% per day.

Intensive therapy.

Intensive therapy methods can be divided into two groups

Priority methods whose effectiveness has been proven (significant reduction in mortality) in clinical practice or in prospective controlled randomized trials:

Antimicrobial therapy;

Infusion and transfusion therapy;

Artificial nutritional support (enteral and parenteral nutrition). 4000 kcal/day is required.

Respiratory support.

Additional methods, the use of which seems to be pathogenetically advisable, but is not generally accepted.

Replacement immunotherapy with intravenous immunoglobulins (Ig G, IgM+IgG);

Extracorporeal detoxification (hemo-, plasmafiltration);

Monitoring the septic process.

Dynamic monitoring of the patient during intensive care should be carried out in three directions:

Monitoring the condition of the main source of infection and the emergence of new ones.

Assessment of the course of systemic inflammatory response syndrome (score assessment of the severity of the patients’ condition).

Analysis of the functional usefulness of individual organs and systems.