In 2016, new definitions of sepsis were published and septic Shock. Since the existing data on epidemiology, the forecast and treatment belongs to states diagnosed in accordance with previously used definitions, as well as due to the fact that the equivalent of the previously used term "heavy sepsis" according to the new nomenclature is "sepsis" in this publication of management These concepts are used in parallel (,). New definitions do not include the term "infection" - below are presented in the traditional sense of the word.

Table 18.8-1. Definition and criteria for diagnostics of sepsis and septic shock

Definitions and criteria	Previous (1991, 2001)	Provided New (2016)
	CVO resulting as a result of infection	life-threatening organ dysfunction caused by the disregulation of the body's response to infection; This answer leads to damage to organs and tissues (corresponds to the previous concept of "heavy sepsis")
heavy sepsis	sepsis causing insufficiency or violation of the function of organs (or system systems → see below); Equivalent of the concept of "sepsis" in the new nomenclature	equivalent is "sepsis" see above
diagnostic Criteria for Organ Dysfunction	used to diagnose heavy sepsis ()	used to diagnose sepsis - sudden increase in the score of the Sofa scale by ≥2 points () A, if there is or suspicious of infection
septic shock	the shape of severe sepsis with the acute insufficiency of blood circulation characterized by the resistant hypotension (systolic arterial pressure<90 мм рт. ст., средние <65 мм рт. ст. или снижение систолического давления на >40 mm RT. Art.) Despite the appropriate infusion therapy (with the need to apply Vazopressors in the future)	sepsis, in which circulatory, cellular and metabolic disorders are so heavy, which significantly increase mortality it is diagnosed if despite the correct infusion therapy is held: 1) hypotension in need of the use of vasopressors to maintain the average blood pressure ≥65 mm Hg. Art., as well as 2) Plasma lactate concentration\u003e 2 mmol / l (18 mg / dl)
scale offered for early detection of patients with high risk of death	not defined, used both CAC criteria and dysfunction of organs, as well as comprising their extended sepsis diagnostic criteria ()	qUICK SOFA score (QSOFA) - ≥2 with the following symptoms: 1) Violation of consciousness b 2) systolic blood pressure ≤100 mm RT. Art. 3) respiratory frequency ≥22 / min
determination of the gravity of the inflammatory response	used in the definition of sepsis - Sirs, i.e. ≥2 with the following symptoms: 1) Temperature of the body\u003e 38 ° C or<36 °C 2) Heart frequency\u003e 90 / Minv 3) breathing frequency\u003e 20 / min or Paco2<32 мм рт. ст. 4) the number of leukocytes\u003e 12 000 / μl or<4000/мкл, или >	it is not given (it has been established that the inflammatory response is only one and not the most important component of the body's reaction for infection; emphasis on organ dysfunction is made that it significantly increases the risk of death)
and in patients without acute organ dysfunction, the result on the Sofa scale is usually 0. b Resume score for Glasgow's coma (→)<15 баллов in may be absent in patients with taking β-blockers. PACO2 - partial carbon dioxide pressure in arterial blood, Ssvo (sirs) - system inflammatory response syndrome based: INTENSIVE CARE MED. 2003; 29: 530-538, as well as jama. 2016; 315: 801-810. DOI: 10.1001 / jama.2016.0287

Table 18.8-2. Traditional diagnostic criteria associated with sepsis organ dysfunction

1) associated with sepsis of tissue hypoperfusion or 2) Dysfunction of organs or systems of organs caused by infection, i.e. ≥1 with below the dysfunctions: a) hypotension caused by sepsis b) lactate concentration\u003e VGN c) diuresis<0,5 мл/кг/ч в течение >2 hours Despite the appropriate infusion therapy d) PAO2 / FIO2<250 мм рт. ст., если легкие не являются очагом инфицирования, либо <200 мм рт. ст., если легкие являются очагом инфицирования e) creatininemia\u003e 176.8 μmol / l (2 mg / dl) e) bilirubinemia\u003e 34.2 μmol / l (2 mg / dl) ё) Number of platelets<100 000/мкл g) coagulopathy (many\u003e 1.5)

a previously proposed criteria for the diagnosis of heavy sepsis. FIO2 - the concentration of oxygen in the inhaled air, expressed in the form of a decimal fraction, the VGN - the upper boundary of the norm, PAO2 is the partial pressure of oxygen in arterial blood

Table 18.8-3. Scale associated with sepsis organ dysfunction (Sofa) A

Organ or system	Result
respiratory system
PAO2 / FIO2, mm Hg. Art. (kPa)				<200 (26,7)б	<100 (13,3)б
chopping blood
number of thrombocytees, × 103 / μl
liver
bilirubinemia, μmol / l (mg / dl)		20–32 (1,2–1,9)	33–101 (2,0–5,9)	102–204 (6,0–11,9)
circulatory system	Garden ≥70 mm Hg.	GARDEN<70 мм рт.ст.	dobutamine (any dose) or dopamine<5в	noraderenalin ≤0.1 or adrenaline ≤0.1, or dopamine 5.1-15V	noraderenalin\u003e 0.1 or adrenaline\u003e 0.1, or dopamine\u003e 15V
nervous system
scale Coma Glasses
kidney
creatininemia, μmol / l (mg / dl) or diuresis, ml / day		110–170 (1,2–1,9)	171–299 (2,0–3,4)	300–440 (3,5–4,9)
a Calculator in Polish - http://www.mp.pl/oit/wpraktyce/show.html?id\u003d57427 b during artificial ventilation of the lungs in the dose of catecholamines given in the ICG / kg / min and used for ≥1 h FIO2 - oxygen concentration in inhaled air, expressed in the form of a decimal fraction, garden - middle blood pressure, PAO2 - partial oxygen pressure in arterial blood based: INTENSIVE CARE MED. 1996; 22: 707-710

Infection - inflammatory response to microorganisms in tissues, liquids or body cavities, which are normal in normal.

Microbiologically confirmed infection - Isolation of pathogenic microorganisms (or the definition of their antigens or genetic material) from liquids or body tissues, which are normally sterile.

Clinical suspicion of infection- Availability clinical symptoms, convincingly indicating infection, for example. Leukocytes in the system fluid fluid, which is normally sterile (except blood), perforation of internal organs, with X-ray pattern of pneumonia in combination with purulent discrepancies with respiratory tract, infected wound.

Polyorgan Dysfunction Syndrome (SPO) - severe dysfunction of organs during an acute disease, indicating the impossibility of maintaining homeostasis without therapeutic intervention.

Bacteremia - live bacteria in the blood. Viremia - viruses are capable of replication in the blood. Fungmia - Living blood mushrooms (Candida's live mushrooms in the blood).

The type of microorganisms is not determining during sepsis, as the microbes should not be present in the blood. In most cases, there are no preceding immunity disorders, although they are the risk factors of sepsis.

Infections and inflammation, causing sepsis, originally relate to various organs, including - abdominal cavity (eg, peritonitis, cholangitis, acute pancreatitis), urinary system (pyelonephritis), respiratory tract (pneumonia), central nervous system (neuroinfection), pericardium, bones and joints, leather and subcutaneous fiber (wounds as a result of injuries, breakingles and postoperative), Reproductive system (including blastocyst infections). The source of infection is often hidden (eg, teeth and periodontal tissue, nasal sinuses, almond, gallbladder, reproductive system, internal abscesses).

Yatrogenic risk factors: Vascular cannulas and catheters, a catheter in the bladder, drainage, implanted prostheses and devices, mechanical ventilation of the lungs, parenteral nutrition, transfusion of infected liquid and blood, wounds and breakdowns, imminent impairment as a result of pharmacological treatment and radiation therapy, etc.

Pathogenesis

Sepsis is an incorrect reaction of the organism of the NA infection with the participation of components of the microorganism and endotoxins, as well as the host by the body of the inflammatory reaction (cytokines, chemokines, eikosanoids produced by the body (cytokines, hemokine) and substances damaging cells (eg, free oxygen radicals ).

Septic shock (hypotension and tissue hypoperfusion) is a consequence of an inflammatory response caused by inflammatory mediators: insufficient filling of the vessels - relative (expanding blood vessels and a decrease in peripheral vascular resistance) and absolute (increase in the permeability of vessels) of hypovolemia, less often - reduced myocardial reductions (usually, during septic Cardiac shock is increased, subject to adequate filling with liquid vessels). Hypotension and hypoperfusion lead to a decrease in the delivery of oxygen to the tissues and their hypoxia. Finally, the decrease in the delivery and use of oxygen increases anaerobic metabolism in cells and leads to lactatecidosis. Other elements of septic shock: acute respiratory distress syndrome (ORDS), acute renal failure, violation of consciousness caused by Izhemia CNS and the impact of inflammation mediators, disorders of the digestive tract - the paralytic obstruction of the intestine due to its ischemia and damage to the mucous membrane, leading to the movement of bacteria from the lumen Gastrointestinal tract in blood (bacterial translocation) and bleeding (hemorrhagic gastropathy and stressful ulcers →, ischemic colitis →), acute hepatic insufficiency →, reduction of adrenal reservoirs (relative adrenal failure).

Clinical picture and natural flow

Sepsis symptoms → Definition and. Other symptoms depend on the initially affected organs. If the progression of an infection does not stop in the early stages of sepsis, the symptoms of dysfunction of other organs begin to appear: the respiratory system (acute respiratory failure - ORDS; →) of the cardiovascular system (hypotension, shock) and kidneys (acute kidney damage, originally preenal →), As well as hemostasis violations (DVS →; initially, as a rule, thrombocytopenia) and metabolic disorders (lactacidosis). If not to start effective treatment, shock is aggravated, polyorgan deficiency develops and death comes.

Table 18.8-4. Extended diagnostic criteria and consequences of sepsis

the presence of infection (confirmed or suspected) and some of the following criteria

general indicators - body temperature\u003e 38 ° C or<36 °C - Tachycardia\u003e 90 / min - Tahipne\u003e 30 / min (or artificial ventilation lungs) - Violations of mental status - Significant edema or positive water balance (\u003e 20 ml / kg / day) - hyperglycemia (\u003e 7.7 mmol / l), in the absence of diabetes

inflammatory indicators - leukocytosis\u003e 12 000 / μl or leukopenia (number of leukocytes<4000/мкл) - Availability\u003e 10% of immature neutrophil forms - C-jet protein\u003e 2 standard deviations from average - prokalcitonin\u003e 2 deviations from average

hemodynamic indicators and indicators of fabric perfusion - reduced blood pressure (systolic<90 мм рт. ст., среднее <70 мм рт. ст., падение систолического на >40 mm RT. Art. In persons with arterial hypertension) - Transcentration of serum lactate\u003e Upper boundaries - slowdown in capillary filling

appearing and increasing symptoms of organ dysfunction - hypoxemia (PAO2 / FIO2<300 мм рт. ст., а если имеются первичные заболевания дыхательной системы <200) - Outragia Oliguria (diuresis<0,5 мл/кг/ч в течение >2 h, despite adequate liquid restation) - increase creatinineine on\u003e 44.2 μmol / l (0.5 mg / dl) for 48 hours - hemostasis disorders (number of platelets<100 000/мкл, МНО >1.5, APTV\u003e 60 s) - Concentration of general bilirubin in blood plasma\u003e 70 μmol / l (4 mg / dl) - paralytic intestinal obstruction (peristalsis is not listened)

DIAGNOSTICS

Additional research methods

1. Laboratory research: To estimate the degree of organ dysfunction (arterial gasometry and venous blood, plasma lactate concentration [Determine within a few hours after the occurrence of severe sepsis], study of hemostasis, renal function indicators and liver), as well as the intensity of the inflammatory process (total detachable blood test, CRB or prokalcitonin [PKT, PCT], currently Significantly less than the ESP; the decrease in the PCT can make an idea of \u200b\u200breducing the duration of antibiotic therapy in patients with diagnosed infection, and the negative result of the PCT may substantiate a decision on the termination of empirical antibacterial therapy in patients who suspected sepsis, but later infection was not confirmed).

2. Microbiological research

1) blood - ≥2 samples, including ≥1 with separately punctured veins and one with each vascular catheter introduced\u003e 48 hours; From all samples it is necessary to hold sowing to identify aerobic and anaerobic pathogens;

2) others depending on the estimated etiology - material from the respiratory tract, urine, other biological fluids (eg, spinal fluid, pleural liquid), smears or selection from the wounds.

3. Visualizing research: X-ray (especially light), ultrasound and CT (especially abdominal cavity).

Diagnostic criteria

It is shown in parallel to carry out etiotropic and symptomatic therapy. First of all, the forecast depends on the rapid beginning to introduce antibiotics and liquids. The initial algorithm of actions (the so-called tasks sets) →.

Table 18.8-5. T. n. "Task Packages" according to Surviving SEPSIS Campaign

For 3 hours: 1) Determine the concentration of lactate in the blood 2) Perform the blood pressure on sowing (before applying antibiotics) 3) Apply antibiotics with a wide range of action 4) Pour 30 ml / kg of crystalloid solutions if hypotension arose or if the concentration of lactate in the blood is ≥4 mmol / l (36 mg / dl).

Within 6 hours: 5) Use vasoconstrictors (with hypotension that does not respond to the initial liquid restation) to keep the average blood pressure (MAP) ≥65 mm Hg. Art. 6) with a stable arterial hypotension, despite the liquid restation (MAP<65 мм рт. ст.), или если начальная концентрация лактата составляет ≥4 ммоль/л (36 мг/дл), занесите в документацию обновлённую оценку волемии и тканевой перфузии, выполненную по одной из следующих методик: a) assessment of life functions and an objective examination of blood circulation and respiration systems, with an assessment of capillary filling, pulse and skin condition b) Performing 2 of the following studies: CLASS, SCV O2, Blood EchoCG Blooding System, Dynamic Assessment Response to Load Loading with Lower Limit Lifting in Back position, or Using Trial Infusion Therapy 7) re-identify the concentration of lactate, if it was at first it was raised a.

CVD - central venous pressure, SCV O2 - oxygen saturation of blood hemoglobin from the upper hollow vein

Etiotropic therapy

1. Antimicrobial therapy:initial (empirical), as soon as possible, that is for 1 h (every hour of delay increases mortality)But before that (if only it is possible and does not slow down treatment by more than 45 minutes) it is necessary to make a fence of the corresponding material for the microbiological research (→ diagnosis). Use ≥1 antibiotics with a wide range of action in / in; Consider activity regarding the most likely etiological factors (bacteria, mushrooms, viruses), penetration into the focus of infection, as well as the local sensitivity of microorganisms. With septic shock at the initial stage, the use of ≥2 antibiotics from different groups active in relation to the most likely bacterial pathogens is recommended. It is not recommended to routine use ≥2 antibiotics from different groups aimed at the same suspect or confirmed pathogens during sepsis or bacteremia, concomitant neutropenia, as well as with severe infections with bacteremia or sepsis without shock. Although in these situations, the use of combined antibiotic therapy is not excluded in order to expand the spectrum of antibacterial action (that is, applications ≥2 antibiotics from different groups active with respect to ≥2 confirmed or suspected bacteria). Combined antibiotic therapy (in the meaning above, that is, aimed to one pathogen) is usually applied if the Pseudomonas or Acinetobacter is infected or confirmed (such a tactic is recommended especially in antibiotic resistant strains), as well as with shock with Bactemey S. pneumoniae (in another situation A β-lactam antibiotic with macrolide is used). Every day it is to assess the state of the patient for the possibility of transition to antibiotic therapy with a narrower spectrum or monotherapy. Under septic shock, such a modification was recommended for several days as the clinical improvement and appearance of signs of infection disappeared; This refers to a combined (directed on the same pathogen) of therapy, both empirical and specific, depending on the sensitivity of pathogens. As soon as possible, specific therapy should be applied (in most cases monotherapy) on the basis of sensitivity to antibiotics. Dosage should take into account the pharmacokinetic and pharmacodynamic characteristics of drugs, eg:

1) The use of large saturated doses - for example. vancomycin;

2) the dosing of some drugs, taking into account the mass of the body or the results of determining the serum concentration - aminoglycosides and vancomycin;

3) consideration of the issue of constant or long-term in / in the introduction of drugs whose action is dependent on time at which their concentration is above MIC is mainly β-lactam antibiotics;

4) the introduction of 1p / d preparations, the action of which depends on their maximum concentration, and having a distinct post-libeotic effect - aminoglycosides;

5) the properties of drugs in patients with sepsis or in a state of septic shock - eg. The increase in the volume of distribution of hydrophilic antibiotics and glomerular filtration (renal clearance) occurring especially in patients subjected to solutions reserved, suggests the idea of \u200b\u200busing higher doses. Duration: Usually 7-10 days (longer, if the response to treatment is slow, it is not possible to completely remove the source of infection, neutropenia → or other immunity disorders, some microorganisms, S. aureus bacteremia; a shorter treatment course can be justified in some patients , especially with a rapid clinical improvement after the sanitation of the focus of infection, located in the abdominal cavity or associated with Stelpsis, as well as with uncomplicated [that is, without anatomical violations] Pyelonephritis). The role of determining the level of procalcitonin in reducing the duration of antibiotic therapy → see above.

2. Elimination of the focus of infection- infected tissues or organs (eg gallbladder, necrotized segment of the intestine), catheters (intravenous catheter, which can be a source of infection, should be removed immediately after new vascular access), implanted prostheses and devices; Drainage of abscesses, empynes and other foci of infection. Preferably, the least invasive, but effective intervention (eg if it is possible, performing percutaneous, and not surgical drainage of abscesses). In the case of infected pancreonecrosis, it is supposed to delay surgical intervention.

Symptomatic treatment

Mandatory under sepsis (according to past terminology - heavy sepsis) and septic shock.

1. Primary anti-deposit measures: Fast start, especially in / in solutions Introduction → See below, as well as evaluation of efficiency are at least as important as tactics according to individual algorithms and achieving target parameters. In addition to improving the general clinical condition (and such simple parameters as the heart rate, blood pressure, the oxygen saturation of the hemoglobin of arterial blood, the frequency of respiration, body temperature, diuresis) is considered to be reduced (normalization) of elevated lactate concentration in patients with hypiperfusia, and Also achieve an average blood pressure ≥65 mm. RT. Art. with septic shock (if vasoconstrictors are used → see below). Previously, the achievement was recommended in the first 6h from the beginning of the treatment of "normal" central venous pressure (CVD; 8-12 mm Hg. Art., Average arterial pressure ≥65 mm Hg. Art., Self-diurea ≥0.5 ml / kg / h and saturation of the hemoglobin of central venous blood oxygen (with the upper vein hollow, SvO2) ≥70% or mixed venous blood ≥65%. Under current recommendations, SSC are not directly listed on all these purposes, although the measurements of the above parameters can serve to evaluate the clinical situation. Recommended However, further hemodynamic assessment (as an assessment of cardiac activity, for example echocardiographic) in doubts about the type of shock (for example, a cardiogenic shock can also develop with septic shock), and also preferred the use of dynamic (and not static) hemodynamic parameters for predicting the response on transfusion of solutions →. If after reaching the target average blood pressure (after transfusion of the solution In the use of vasopressors) during the first few hours, a decrease in the concentration of lactate (or target level of oxygen saturation of hemoglobin of venous blood) should be considered expediency, depending on the circumstances (heart rate, the function of the left ventricle, the response to the introduction of solutions, the hemoglobin level) , ≥1 Of the following measures: Further transfusion of the liquid, transfusion of the erythrocyte mass in order to obtain hematocrit ≥30%, Using Dobutamine (Max. dose of 20 μg / kg / min).

2. Treatment of violations of the cardiovascular system

1) proper filling of the vascular channel with solutions - in patients with tissue hypoperfousin and suspected hypovolemia it is necessary to start infusion from the introduction of crystalloids in the amount of ≥30 ml/kg B. the current of the first 3 hours, with simultaneous control over the signs of hypervolemia. Some patients may need fast (or later) overflowing a large amount of fluid. Large volumes of fluid (eg\u003e 30 ml / kg) should be administered portion (eg, 200-500 ml), each time after their transfusion should be assessed with the response to treatment (see also). In SSC Recommendations (2016), there are no data on the advantage of balanced crystalloids with respect to 0.9% NaCl (but, as a rule, balanced solutions are preferred, especially if necessary in / in the introduction of large volumes →), but preference is given to crystalloids in relation to solutions gelatin. The latter, however, do not have such contraindications as hydroxyethyl storage solutions (GEC). It is recommended that the albumin solutions are transfused (as a rule with a concentration of 4% or 5%) in addition to the transfusion of crystalloids in the initial period and with further therapy with solutions in patients who need to transfusion of large volumes of crystalloids.

2) Vazopressors - norepinephrine (preferable), with ineffectiveness should be added vasopressin or adrenaline; Vasopressin can also be applied to reduce the dose of norepinenaline. Indications: Resistant hypotension, despite the transfusion of the corresponding volume of fluid. It should be administered (as quickly as possible) through the catheter introduced into a hollow vein, and monitor blood pressure by an invasive method (enter the catheter in the artery). The use of dopamine is proposed to limit the patient's minor group, especially with bradycardia and reduced cardiac emissions, as well as with a low risk of cardiac arrhythmia.

3) treatment that increases the reduction of myocardium - dobutamine: It should be considered the feasibility of administration in patients with hypoperfusion, which remains despite the appropriate hydration and the use of vasopressors. At dosage (→ 131), it is necessary to take into account that the purpose is to eliminate the hypoperfusion. Introduction should be stopped by increasing hypotension and / or arrhythmia.

3. Treatment of respiratory failure→ Usually need artificial ventilation of the lungs. Treatment of pneumonia →.

4. Treatment of renal failure: The main importance is the stabilization of the activity of the cardiovascular system (normalization of blood pressure); If necessary, replacement therapy (not established whether the early start is more efficient, but most likely it is not recommended if Oliguria and hyperrematininemia are the only indicators to renal renal therapy).

5. Treatment acidoza: Aims to eliminate the cause. Leaving the pathophysiological aspects can be assigned NaHCO3 to / in blood pH<7,15; но клинические эффекты не определены.

6. Corticaterapy: If, despite adequate hydration and the use of vasopressors, hypotension is preserved, it is possible to consider in / to the purpose of the hydrocortisone 200 mg / day (at least before the elimination of the shock). If the hydrocortisone is not available and another glucocorticoid is used without a substantial mineralocorticoid action, it is additionally necessary to assign a 50 μg of 1 × per day (which can also be used in combination with hydrocortisone).

7. Control of glycemia:in the event of a hyperglycemia caused by heavy sepsis (\u003e 10 mmol / l in 2 consecutive measurements), it is necessary to assign insulin (usually in / in infusion); The goal is glycemia<10 ммоль/л (180 мг/дл), чем <6,1 ммоль/л (110 мг/дл). В начальной фазе лечения инсулином требуется контроль гликемию каждые 1–2 ч, a после стабилизации - каждые 4–6 ч. Следует избегать гипогликемии. Лабораторные исследования капиллярной крови на гликемию могут быть у таких пациентов ошибочны. У пациентов с артериальным катетером для прикроватного определения гликемии рекомендуется набирать кровь из катетера (не капиллярную).

8. Additional treatment

1) blood transfusion

a) erythrocyte mass if hemoglobin<7 г/дл, для достижения концентрации 7,0–9,0 г/дл; исключения: переливание эритроцитарной массы при гемоглобине >7 g / dl if there is a tissue hypoperfusion, active bleeding or significant ischemic heart disease;

b) platelet concentrate - regardless of other factors, if the number of platelets is ≤10 000 / μl; Transfusion can be useful if the number of platelets is 10,000-20,000 / μl and there is a state of increased risk of bleeding (including sepsis or septic shock); Conducting invasive procedures may require the number of platelets ≥50 000 / μl;

c) freshly frozen plasma and cryoprecipitate - mainly when there is active bleeding or invasive procedures are planned;

2) Power - as far as possible entering, in a portable patient quantity (not necessarily satisfy the complete need for calories);

3) prevention of stressful ulcers- inhibitor of proton pump or H2-block in patients with bleeding risk factors (seriously ill patients are coagulopathy and mechanical ventilation of the lungs, lasting\u003e 48 hours);

4) prevention of venous thromboembolic disease(VTE) →. Pharmacological prophylaxis must be used if there are no contraindications due to bleeding or high risk of its occurrence; It is recommended to use NMGs than fractionated heparin, as well as, if possible, the beginning of mechanical prophylaxis (only in the presence of contraindications to pharmacological prophylaxis).

5) algorithm of action during mechanical ventilation l HS- in all. The use of sedatives in as little doses as possible, providing the established (as much as possible tolerant) of the sedation, avoid the muscle relaxants with the exception of the ORDS (with ORDS with PAO2 / FIO2<150 мм рт. ст. рекомендуется рассмотреть целесообразность их введения до 48 ч), показано приподнятое положение изголовья кровати на 30–45° с целью предотвращения ИВЛ-ассоциированной пневмонии.

6) Treatment of DVS → - The main value is ethiotropic treatment of sepsis.

Despite all the measures of the epidemiological regime and the use of modern antibiotics caused by nosocomial causative agents, hospital infections continue to be one of the main causes of death in patients of resuscitation and intensive care departments. These infections are diagnosed in patients therapeutic, obstetric and gynecological, surgical profiles.

The frequency of heavy sepsis in resuscitation and intensive care departments everywhere is about 18%, and septic shock - 3-4%. The incidence rate is currently no tendency to reduce, and the incidence of hospital infections increases from year to year by 3-9%. At the same time, mortality reaches 19-40% with a serious sepsis, and in septic shock - 70%, and today, in the era of antibiotics, mortality from septic complications is actually comparable to the one that was noted in the era, when there were no antibiotics at all.

It is significant that over the past two decades, mortality in generalized forms of hospital infections - severe sepsis and septic shock is also not sustained. This is observed in the presence of a workable concept of sepsis (the concept of a systemic inflammatory response), the criteria for the diagnosis of its most severe clinical forms and modern highly efficient antibiotics as a means of conservative therapy.

On the contrary, there is a tendency to increase mortality in septic patients (according to V. G. Bochorishvili, and T. V. Bochorishvili and J. A. Child The mortality from Sepsis over the years after the wording of consensus at the Chicago conciliation has increased at least three times), What attaches a particular relevance to sepsis.

The infectious process in which the pathological state is developing, which is identified as sepsis, characterizes a number of features. In the sepsis, the pathological process initiated by the infectious heart rate due to the inadequacy of the body's protective forces (first of all systems of natural / non-specific resistance) is manifested by generalized dissemination of the infectious principle in the conditions of increasing general immunosuppression, which leads to the development and deepening of polyorgan insolvency in the future - severe sepsis develops . The outcome can be septic shock.

In the genesis of sepsis, the fact that the patient's body loses the ability to localize and suppress infectious pathogens and / or neutralization of their exo- and endotoxins. Simultaneously with the inadequacy of the functioning of the mechanisms to counter infection and the development of the insolvency of these mechanisms, conditions arise for a permanent or periodic (repeated) breakthrough of pathogens and their toxins from natural reservoirs and / or infectious foci into common bloodstream with the development of the systemic response of the body, accompanied by the generalization of inflammation.

Then the direct, as well as indirect damage to vital organs. From now on, sepsis becomes heavy. The severity of the state of such patients is determined by the pace of development of polyorgan dysfunction, primarily the number of organ-functional systems involved in the formation of this state. The progression of these processes is extremely dangerous and significantly increases the risk of fatal outcome.

The development of polyorgan dysfunction is a nodal point of pathogenesis of generalized forms of infectious complications, marking the fundamental transformation of the clinical state of the patient.

In the formation and development of polyorgan dysfunction, depending on the initial state of the body (the level of its immunological compromise, the characteristics of the organization of natural resistance systems, and the more widely - biological reactivity of the body), as well as the virulence of pathogens, the choice of fundamentally new biological response algorithms to the extraordinary Situation. If the response strategy is inadequate, then the factors and mechanisms of protection become damage agents, and the patient's condition should be assessed as critical.

Characteristic of sepsis as a special form of an infection response

Clinical diagnostic signs

As already noted, sepsis can develop as a pathological process accompanying various diseases that are clinically or bacteriologically regarded as infectious. It can also be a complication of diseases, the main link of the pathogenesis of which is the impact of the traumatic factor - surgical operation (surgical sepsis), mechanical, thermal and radial injury.

Sepsis is possible in patients who are weakened by an acute or chronic somatic disease (therapeutic sepsis). Since the intestines located in the abdominal cavity is the natural reservoir of microorganisms, which under certain conditions (including diseases of the abdominal organs) can overcome the intestinal barrier, then abdominal sepsis are isolated into a separate clinical category. In this connection, sepsis cannot be considered a separate nosological unit, this pathology should be regarded as an option of complicated clinical flow of infectious and noncommunicable diseases.

Clinical picture of Sepsis

Clinical manifestations of sepsis can vary in fairly wide limits: from insignificant symptoms to an extremely severe (critical) state, in which adequate intensive therapy becomes a matter of preserving the life of the patient. The late detection of sepsis at the transformation phase into a heavy clinical form is fraught with irreversible consequences, since the predicted mortality in such patients exceeds 40% (real mortality of certain authors estimates, reaches 80%).

The most early detection of sepsis is based on septic alert, attention to the data of carefully collected anamnesis and the results of a targeted clinical examination: visual, objective - physical and laboratory. It is necessary to strive to take into account all possible manifestations of sepsis. It is extremely desirable to track the dynamics of detected deviations.

Sirs-criteria are necessarily considered taking into account the characteristics of fever, symptoms of intoxication, changes in blood pattern, liver size and spleen. At the same time, it is necessary to characterize the possible gate of infection, primary foci and strive to identify foci of dropout. These manifestations of hemorrhagic rash and clinical signs of the development of endothelial dysfunction are noteworthy.

The following processes are indicated about the weighing of the clinical picture of sepsis: the progressive spread of secondary metastatic foci and the severity of organic pathology with the manifestation of extreme forms of polyorganized dysfunction in the form of cardiovascular, respiratory, renal, immune failure. In the development of septic shock and the combination of septic shock, the risk of lethal exodus increases twice, exceeding 80%.

Following the principles of septic alertness, early diagnosis and advanced therapy in aggregate with careful, and if necessary, multiple bacteriological control, including the patient's blood pressure for studying the hemoculture at the height of the fevering reaction, ensures timely recognition of sepsis, its favorable forecast and increases the effectiveness of treatment.

The clinical picture of sepsis is primarily due to the phenomena of endo- (auto-) toxicosis and is usually manifested by intermittent fever, chills, heat, sweating, extremely severe common state of the patient. Short-term excitement is replaced by infringement. The skin is pale, often with hemorrhages.

Fever is a systemic response to an infection, which to a certain extent contributes to an increase in the general resistance of the body. In most patients with sepsis, even at the beginning of its development proceeds with an increase in temperature, which can reach the hyperpyractic values \u200b\u200b(\u003e 40 ° C). Fever characterize large daily fluctuations in body temperature with several peaks, the duration of which can reach several hours. Overall of different intensity can be observed, as well as muscular trembling. If there is a critical temperature decrease, it is accompanied by a pouring later.

When analyzing the temperature curves, a remote fever with daily fluctuations in 1-2 ° C is detected. If septicopyiamia is developing with multiple focal foci, daily temperature fluctuations can reach 3-4 ° C, and the fever becomes hectic with the maximum temperature in the evening. With a sepsis flowing with hectic fever, a phenomenon of an advanced tachycardia is recorded, in which heart abbreviations are rapidly random than the temperature increases. The high fever corresponds to pronounced intoxication, at the peak of increasing the temperature, the condition of patients with sepsis deteriorates, and when the temperature decreases.

In elderly, the temperature reaction is smoothed, only a subfebrile temperature can be recorded, but the cessation of a feverish period in older people does not always indicate the completion of the septic process. When sepsis, the elderly and in newborns, as well as with concomitant Uremia and alcoholics, hypothermia can be registered. The development of hypothermia in septic patients who had previously manifest a hyperthermic reaction are prognostically unfavorable.

Manifestation of intoxication

Signs of intoxication are most pronounced at the height of fever. With bacteremia in the blood, endotoxins of pathogens are accumulated, as well as the products of the autolysis of cells and tissues, with the toxic effects of which most of the symptoms are associated. If the consciousness of patients is preserved, they complain about severe headaches, dizziness, decay of forces. Vomiting may develop. Appetite is absent, characteristic insomnia.

Some patients can be excited, non-critical in assessing their condition. Possible loss of consciousness, nonsense, comatose state. With a multi-day fever, patients are injured and mental depression develops. Signs of brain shell irritation may be recorded.

From the side of the blood pattern under sepsis, the main changes are determined by the degree of severity of toxicosis and metabolic disorders. The following manifestations are characteristic: leukocytosis of different seventences (in some patients in peripheral blood (in some patients in peripheral blood, are determined by\u003e 20 x 10x9 / l leukocytes), neutropyl displays with a shift towards immature cellular forms, toxic neutrophil grain, the appearance of a voltage and vaculation of the cytoplasm.

With subsequent surveys of peripheral blood, the number of leukocytes does not increase, on the contrary, there may be a decrease in this indicator - leukopenia develops (< 4 х 10х9/л лейкоцитов), что может сопровождаться нейтропенией. Возможно уменьшение содержания лимфоцитов - абсолютная лимфопения (< 1,2 х 109/л лимфоцитов).

The progressive thrombocytopenia is associated with the threat of thrombosis and the risk of DVS-syndrome. The trend towards thrombocytopenia is often revealed already in the early deadlines for the development of sepsis, a tendency towards anemia is characteristic of the later deadlines. Thrombocytopenia under sepsis is stated in 56% of patients. The products of erythrocytes under sepsis are reduced, and anemia is observed in all cases, with 45% of sepsis patients with hemoglobin content below 80 g / l, which is prognostically unfavorable. In the early stages of Sepsis, red blood indicators as the criteria for assessing the severity of the patient's condition and the forecast of possible outcome are uninformative.

Limphopal, monocytosis, anemia of the average and serious degree correspond to the sepsis clinic, for heavy sepsis is characterized by a combination of lymphopenia with monocytopenia. In patients with severe sepsis, the process of the apoptosis of lymphocytes is intense, as well as a sharply reduced percentage of monocytes, highly expressing the HLA-DR marker, in peripheral blood.

Hepato and splenomegaly

Splenomegaly at sepsis is determined significantly more often than the increase in the liver. The spleen increases already in the early stages of sepsis development, which can be considered as an early diagnostic sign, which is the most constant of the objective criteria for the weighing of sepsis. Splenomegaly can be determined by percussion of abdominal organs and with ultrasound examination.

Hemorrhagic rash

During sepsis in a third of patients, rashes (from point echimosis to drain erytimes and large hemorrhagically necrotic elements on the skin). By the nature of the rash can sometimes assume the etiology of sepsis. Thus, petechia usually appear in meningococcal sepsis, gangrenous ecctim - with neutropenia against the background of sepsis caused by a blue rod. Drain erythema with peeling is observed with toxic shock caused by staphylococcus aureus or streptococcus pyogenes.

The rash appears in the early deadlines for the development of sepsis, more often localized on the front surface chest, on stomach and hands. The skin around the elements of the rash is not changed. In a long time, rash is pale. Itching during rashes is usually absent. The causes of hemorrhagic rashes are microcirculation disorders, the development of common vasculitis and the formation of multiple blood microtrombosis, so rash with a sepsis pathognomonic.

Acute gastroenteritis

Acute gastroenteritis is a frequent component of sepsis. It is manifested by nausea, vomiting, which does not bring relief patients; Paralytic intestinal obstruction can develop. Bleeding from the upper departments of the gastrointestinal tract due to the formation of stressful ulcers.

In patients with sepsis, cholestatic jaundice often occurs, the reason for which the violations of the functions of hepatocytes and bile capillaries are served. Often jaundice precedes other symptoms of sepsis, the level of direct bilirubin increases in the blood, registered high values Alkaline phosphatase activity. With a pronounced or long-lasting decrease in the blood pressure, ischemic lesions of the liver and intestines.

Primary focus of infection

Localized purulent-inflammatory foci, which cause the subsequent generalization of the infectious process, is customary to be called primary. When sepsis, in conditions of generalization of inflammation and failure of immunoreactivity systems, the body loses the ability to localize infection and control its manifestations outside the primary and other infectious foci.

The primary focus can correspond to the entrance gate of infection, but non-compliance is quite often stated. The presence of a primary inflammatory focus and its transformation in some cases precede the development of sepsis. The primary focus of infection does not predetermine the severity of general manifestations, and its rejection does not prevent the progression of the sepsis already started. The development of processes in the primary focus and the total course of sepsis in many cases asynchronously.

Septic metastases

The results of post-mortem morphological studies show that purulent metastases can affect any organ, but especially often septic foci are detected in the kidneys, lungs and liver. In the patients died from sepsis, metastatic purulent embols, or abscesses are found in the brain and heart, subcutaneous tissue and muscles.

Metastation of the pathogen from the primary hearth with the formation of secondary foci of infection can cause a light infarction, purulent pleurisy, lung gangrene, diffuse interstitial myocarditis, endocarditis, pericarditis, hemorrhagic jade, purulent cystitis, purulent peelith and paranefrit, brain abscesses and purulent meningitis, purulent arthritis, osteomyelitis , Flegmons and abscesses in the muscles.

Localization of so-called foci of dropout (secondary foci) depends on the location of the primary focus of infection. If the primary focus is on the valves of the heart, it is more often observed in the brain and kidneys. Infected clomes usually determine metastasis in the lungs. There is no doubt that with surgical sepsis, purulent foci (regardless of whether they are primary or secondary) play a leading role in the pathogenesis, their presence determines the clinical picture of the disease. The severity of the patient's condition with sepsis directly correlates with the fact of the presence of purulent foci.

According to M.V. Greeneva et al., There is no particular sense to clinically allocate such forms of sepsis as septicemia and septicopemia. Sepsis begins with the generalization of the inflammatory response (overcoming the relative autonomy of the primary inflammatory hearth and the inadequacy (redundancy) of the organism's systemic response according to the strategy of the acute inflammation phase), then septicemia is developing.

If the patient does not die in the formation of early polyorgan insufficiency and lives until the next phase of the development of the pathological process, the female remote foci appear. After their adequate drainage, septicemia can be marked again, then the female foci again is formed. The process acquires the nature of the vicious circle in its promotion to complete immune insolvency (late or septic polyorgan deficiency), and septicemia and septicopemia are only two phases of a single pathological process, we naturally flowing alone to another.

Polyorgan disorders

The clinical manifestations of the emerging polyorgan dysfunction are mostly determined by the development and prevalence of dysfunction of the endothelium of vessels and coagulopathy, which is accompanied by the development of systemic vasculitis, as well as intense cell death in vital organs of necrobiosis and apoptosis. These two components make the greatest contribution to the genesis of organ disorders and are universal as a component of the system alteration.

Damage to the endothelial chipping of vessels of many organs in the event of a further progression of the pathological process against the background of generalized inflammation and disorganization immune system Inevitably poured into deep organ-system disorders, including on removal from the primary focus - polyorgan dysfunction develops, and then insufficiency (PON).

The formation of Pon is always indicative of generalization of basic pathological processes and determines the difficult course of sepsis with the threat of death due to the defeat of vital organs. Independent recovery becomes impossible.

Usually sepsis develops with increasing clinical manifestations - aciquity. Clinical manifestations of the pion syndrome are also diverse. The most characteristic of the development of cardiovascular, respiratory and renal failure. The most problematic body is light. Hemodynamic disorders with a drop of blood pressure, tachycardia and the defeat of the heart muscle are rapidly progressing. More often and faster Pon develops with gram-negative sepsis.

Currently, with a sepsis characteristic as an option of the course of the infectious process, the main focus of specialists focuses on determining the type of pathogen, the evaluation of its virulent qualities, the ranking of the process of generalizing the inflammatory response on consistently developing stages (the beginning of invasion and colonization of the pathogen, the development of infection with the local inflammatory response and the formation of the hearth Inflammation, breakthrough of the relative autonomy of the hearth and the development of a systemic inflammatory response / sepsis /, addition of polyorganized dysfunction / severe sepsis /, escalation of damage to many organs and transformation into a septic shock).

It is also very significant to assess the gravity of the clinical state of patients in the context of the designated stages of the development of the pathological process. At these nodal moments, the concept of the diagnosis of sepsis, professing foreign academic science over the last decades, was built.

The lack of effective immunity to conditionally pathogenic pathogens in the development of such severe infectious complications such as sepsis, severe sepsis and septic shock, in patients of various profiles are confirmed by the fact of the generalization of infection. It will not be an exaggeration approval that, according to its pathogenetic essence, sepsis is, above all, immune inconsistency, in which the conditionally pathogenic flora becomes aggressive and capable of causeing a generalized formation formation.

Recommended clinical and laboratory indicators of the stages of the development of the septic process

From the above, it follows that the definition of key manifestations of sepsis, as well as the staging of pathological processes, characterizing the severity of the clinical state of septic patients, is the main medical task. The choice of the optimal amount of medical measures, as well as tactics of therapy, depends on the right solution to this task. This determines the success of treatment.

On the methodology that should be guided in assessing the severity of septic patients, including signs of dysfunction of organo-functional systems, it is possible to make a submission based on the recommendations on the algorithm for determining sepsis.

Infectious focus

• A microbiotic phenomenon characterized by the development of classical signs of inflammation (redness, swelling, soreness, local temperature increase) from the macroorganism for the presence of microorganisms or on their penetration in usually sterile tissue.

Bacteremia

• The presence of live bacteria in the blood.

System inflammatory response (s)

Systemic inflammatory response of the body for one of the potent and significant factors (infection, pancreatitis, injury or other tissue damage, ischemia), which is manifested by two or more signs (Sirs criteria):

• fever\u003e 38 ° C or hypothermia< 36 °С
• tachycardia (CSS\u003e 90 UD / min)
• tahipne (ChDD\u003e 20 in 1 min or Raso2< 32 мм рт. ст.)
• blood leukocytes\u003e 12 × 109 / l or< 4 × 109/л или наличие незрелых форм клеток > 10%.

• The presence of a focus of infection and manifestation of a systemic inflammatory reaction with two or more signs of Sirs.

Heavy sepsis

• Septice, combined with organ dysfunction, disruption of tissue perfusion or hypotension. Perfusion disorders may include (but not limited to these indicators) lactate acidosis, oliguria or sharp changes in mental status. Hypotension is easily eliminated through adequate infusion therapy. The syndrome of polyorganized dysfunction (MODS) is the damage to the functions of more than 2 organs and systems, while homeostasis cannot be saved without interference from the outside.

Septic shock

• Heavy sepsis with fabric and organic hypoperfusia, as well as with arterial hypotension, which is not eliminated through adequate infusion therapy. In the treatment of vasoconstrictor or inotropic drugs, hypotension may not be, however, there are violations of perfusion.

Thus, to reasonably talk about the development of sepsis, it is necessary to have signs of its (\u003e 2 criterion Sirs), bacteremia (test of positive hemoculture) and / or infectious hearth. The presence of an infectious focus uniquely determines the nature of the pathological process. Signs (criteria) It is manifest the fact of penetration of mediators of inflammation into systemic circulation.

Bacteremia is not an absolute diagnostic criterion, since the most severe patients with a scrupulous observance of blood intake techniques and the use of modern technologies for the detection of microorganisms The frequency of positive results of the evaluation of hemocultures for the presence of microorganisms is usually within 40-60%.

On the contrary, the signs of organosystem dysfunction are extremely important, since the presence of these signs confirms the progression of the process of spreading an infectious-inflammatory reaction beyond the primary hearth and involvement in the pathological process of target organs, in the tissues of which universal damage mechanisms are implemented, with sepsis transformation into heavy sepsis or septic shock.

Conditions for the development of sepsis, its components and predisposing factors

It is necessary to emphasize that the emergence and development of both therapeutic and surgical sepsis is due primarily to the infectious nature of pathogenic microorganisms. Without an infectious pathogen capable of invasion, the development of sepsis is impossible. Ultimately, as the result of infectious effects there is a situation of insolvency of anti-infective protection mechanisms with the formation of regulatory, and more often the structural-morphological disorganization of the immune system.

Consequently, the insufficiency of protective mechanisms to counter infection provided by both the factors of constitutional immunity and mechanisms of acquired (adaptive) immunity are a prerequisite condition for the development of sepsis. It is clear that the inconsistency of the immune system acquires the leading importance when it comes to serious sepsis.

The role of colonization of microorganisms and infection

Colonization of potential pathogens and infection - predisposing factors for the development of sepsis. The value of colonization is especially large if sepsis is caused by a conditional pathogenic flora. In this case, under conditions of a sharp weakening of the barrier functions of the epithelium of the mucous membranes, which are provided by the factors and mechanisms of mucosal immunity, it is possible to translocate the bacterial flora and the pathogenic characteristics of the products of the life of microorganisms, followed by their propagation of the body internal environments.

The role of the presence of living microorganisms in system circulation. The presence of living microorganisms (more often bacteria - bacteremia) in the blood is important, but not necessarily and not the only condition for the development of sepsis. If there are manifestations of a generalized inflammatory reaction, then bacteremia established by microbiological analysis methods is undoubtedly a confirmation of the fact of the development of sepsis.

In the absence of a causative agent at a primary bacteriological study, repeated sowing samples with an in-depth microbiological study are needed, including those implemented before the start of antibiotic therapy.

Metastasising infection

The generalization of infection with the formation of foci of dropout indicates its progressive propagation by hematogenic means. The deadlines for the occurrence of secondary foci and their localization can vary widely, which corresponds to the acyclic flow of sepsis.

Formation of fighters - one of clinical options The flow of sepsis, determined by the nature of microflora and the peculiarities of the patient. This is a possible, but not mandatory criterion for the presence of sepsis. However, the appearance of foci of metastasis has not only diagnostic, but also prognostic value, since when metastasis, the sepsis weight increases progressively and increases the probability of the development of Pon.

System inflammatory answer

System inflammatory response (its) is a mandatory component of sepsis. System inflammatory response syndrome (CBE / SIRS /) clinically manifests the penetration of pathogens, cytokines and other systemic inflammation mediators in the bloodstream. According to its pathogenetic essence, its activation immune dysfunction, in particular, the fact of the appearance of this syndrome states the fact of the loss of the infectious heart rate with its relative autonomy with the transition of inflammation into the system form.

General Immunodepression

General immunosuppression is an equally significant component of the pathogenesis of sepsis, as well as its. In sepsis, immunosuppression is also systemic in nature, many structural components of the immune system are depressed, first of all cells that provide regulatory and effector mechanisms of immunoreactivity, which has the consequence of inconsistency of both constitutional and adaptive immunity. The systemic nature of the general immunosuppression allows the use of terms "total" and "systemic" as synonyms.

Mechanisms for the formation and deepening of general immunosuppression are multicomponent, therefore, under sepsis, the total immunosuppression has various clinical manifestations, which is determined by the severity of deploying pathological processes.

Clinically, the general immunosuppression is manifested by the growth of signs of endo-(auto-) toxicosis, the occurrence of secondary septic foci, or the development of visceral infectious complications, in particular, nosocomial pneumonia. The microbiological feature of the general immunosuppression is shown by the microbial landscape with the predominance of a conditionally pathogenic flora or its consistent replacement of hospital strains of microorganisms.

The development of general immunosuppression is indicated: pancytopenia, leukopenia, lymphopenia, increasing the leukocyte index of intoxication and growth in the blood plasma concentration of medium peptides, an increase in blood plasma of the level of "anti-inflammatory" cytokines and other immunosuppressor factors (glucocorticoids, PGE2, TGF1, IL-1RA, IL-4, IL-6, IL-10).

Heavy forms of immunosuppression can not be compensated independently, which dictates the need for mandatory use in the treatment of such patients of immunoactive drugs of the substitutionary type of action.

The main stars of the pathogenesis of sepsis

The ideas about the pathogenesis of sepsis cannot be considered completely formulated, although each surgeon and a doctor of extreme medicine know about the role of a generalized inflammatory response. It is also clear that the pathogenesis of sepsis is complicated and presented by pathogenetic links affecting almost all organic-functional systems of the body, especially when it comes to severe sepsis and septic shock.

In the pathogenesis of these most severe forms of infectious complications, the main links can be allocated. These links are:

• bacteremia and microbial toxemia (in extreme forms of septic shock),
• endo- (auto-) toxicosis,
• system destructive vasculitis,
• intensification of hypercoagulation processes with the subsequent development of coagulopathy, thrombocytopenia of consumption and thrombohemorgic syndrome (in the extreme forms of DVS syndrome),
• pronounced immune dysfunction / deficiency as an activation (system inflammatory response) and depressive type (system immunosuppression).

Simultaneous manifestation of immune disorders of both activation and depressive orientation allows you to talk about immune dissonance. With severe sepsis, these pathogenetic links may have an extreme degree of severity, causing the formation of mono- and polyorganic insufficiency (insolvency) of organic-functional systems of the body, which is its attribute sign.

Inside the developing dysfunction of the immune system - secondary immune failure - with full right, it is necessary to refer to the number of major pathogenetic units of heavy sepsis. In turn, inherent components of secondary immune failure during sepsis are:

• disorders of the main processes of regulation of immunoreactivity and the subsequent structural-functional disintegration of the immune system;
• general immunosuppression;
• violation of the participation of the immune system in integration and regulatory interactions with the basic organic-physiological systems of the body.

The depth and globality of immune disorders formed during the heavy sepside, as well as the direct participation of immune nature factors in the process of systemic alteration, it is clearly transformed into immune dysfunction into the most important component of Pon. The most significant system processes that are directly related to the PAT Pathogenesis are the imbalance of the components of the immune system as an indicator of its disintegration and the total (systemic) immunosuppression as an insolvency indicator.

The identification of a specific structural-morphological level of the immune system with such a pronounced dysfunction has a secondary value. However, there is no doubt that disorders are deeply affected by its core - a system of interacting immunoreactivity cells, primarily mononuclear cells with different functional specialization.

System inflammatory response: pathogenesis and evaluation

It is formed as a systemic reaction of the body on extraordinary effects. The mechanisms of implementation are launched when exposed to the initiating factor (injury, ischemia, infection), then its severity is constantly increasing by activating the puisoral systems of cascade proteyolysis of plasma and stadium cell activation, including monocytes / macrophages, neutrophils, lymphocytes, platelets, and endothelium cellular liner length. These cells produce both cytokines and other activation mediators, together form a network of interrelated functional links - cytokine network.

With excessive activation of the cytokine network, both exogenous and endogenic products, inflammation with the loss of the protective function of the local inflammatory focus occurs. At the same time, the effects of systemic alteration are growing, the severity of which is maximum at Pon.

It should be considered as an overweight response of the acute phase. The main components of a systemic, or generalized inflammatory response of the body to infection are the following processes:

• activation of neutrophils and monocytes of blood, tissue and resident macrophages, as well as kravel cells (venous liver sinuses) lipopolysaccharide endotoxin gram-negative bacteria and other bacterial toxins, bacterial DNA and IL-1BET;
• synthesis of positive globulins of an acute phase response and other adaptogen proteins;
• release wide spectrum "Pro-inflammatory" cytokines (TNF, IL-8, IL-12, IL-17), IL-6 (multifunctional cytokine in the early stages of activation of the response of the acute phase, and later - an immunosuppressant factor), as well as other mediators;
• phagocytosis, presentation and processing of antigens;
• activation of lymphocytes by monocures (in particular, TH1 under the influence of IL-1Bet);
• independent antigen expression on IL-2 receptor cells and subsequent proliferation of T-lymphocytes;
• secretion IL-12 and IFNY generation with additional activation of macrophages;
• activation of B-lymphocytes under the influence of IL-6;
• activation of the complement system.

The subsequent activation of a wide range of cells and endothelium of blood vessels with excessive products of classical "pro-inflammatory" cytokines, as well as other inflammatory mediators lead to a sharp generalization of systemic inflammation with hypercitoniamia, hypotension, shock and early Pon. Obviously, the immune system is involved in the implementation of its development and in its development there is dysfunction of the immune activation type system.

Mobilization of immunoreactivity on the scenario of the excess response of the acute phase is simultaneously the preparatory stage of the adaptive (dependent antigenic stimulation) of the immune system response, so the inadequacy of the "transimary" response is a serious prerequisite for the formation of immune disorders in the process of implementing an adaptive response.

Factors and mechanisms of damage to cells and tissues with its and pon

Molecular structural components and factors of infectious pathogens, components of its metabolism, regulatory factors (for example, cell adhesion molecules and heat shock proteins), excessively activated when mobilizing the cell immunoreactivity, as well as cell-effector cells can be implemented by agents alteration.

Typically, the factors of damage under its and pont protrude:

• secreted factors of the virulence of etiopathogen (exotoxins and extracellular enzymes of grappositive microorganisms), Superantigenes;
• structural antigens of microorganisms (lipopolysaccharide endotoxins of gramnegative bacteria, peptidoglycans of various pathogens);
• components of the watchtone plasma polysisystem;
• mediators of Arachidon Cascade and other Eicosanoids;
• cytokines;
• leukokinins;
• lysosomal and other intracellular enzymes;
• cell autolysis products (medium peptides);
• active forms of oxygen and other free radicals;
• nitrogen oxide;
• excessively activated cytotoxic, obese and endothelial cells.

The presence of the bacterial pathogens at the same time many and special factors of virulence - formyl peptides, exotomins and secreted enzymes, enterotoxins, gemolysins-proteoglycans, lipotheychic acid, Superantigen is an additional contribution to the initiation of the stem pathogenesis of sepsis and predetermines the features of its flow related to infection with the specific pathogen.

These factors are of particular importance if there are staphylococci, enterococci and a cinema wand with the pathogens of sepsis. Thus, leukocidin of the blue stick is capable of providing a direct cytotoxic effect, initiating swelling and cells of cells. This exotoxin also exhibits selective cytotoxic activity against immunoreactive cells, in particular it may cause neutropenia.

The presence of such extremely active biological substances in the spectrum of the virulence of potential causative agents of such extremely active biological substances as Superantigenes is extremely important. Superantigens affect the T-lymphocytes outside the zone of the antigenpacy fragment of their cell receptor and the large number of T-lymphocytes, which release the excess IL-2, are polyclonally activated. Next, the cytokine network and monocytes / macrophages are excessively activated, which leads to hyperproduction of various mediators and a fulminant inflammatory response. The main effector mediator of subsequent cellular and tissue damage (secondary alteration reactions) is TNFA. After the activation of the T-lymphocytes, T-lymphocytes remains for a long time remaining.

Bacterial Supporties are also powerful pyrogens and at the same time show biological activity of exotoxins. They are able to initiate clinical manifestations of toxic shock syndrome. These manifestations are similar, but are not identical to the clinical manifestations of septic (endotoxic) shock.

For shock caused by bacterial exotoxins, characteristic: pronounced fever, diarrhea, indomitable vomiting, hypotension, erythrodermia, and in the case when shock complicates staphylococcal or anaerobic wound infection, is the desquamation of the skin around the wound. Involvement in the pathological process of target shock organs forms polyorgan insolvency.

In the surgical hospitals of toxic shock syndrome, the signs of which are pronounced fever, hemorrhagic bulls and erythematous skin rashes, as well as the development of disseminated intravascular coagulation and respiratory distress-syndrome of adults, with an outcome in the progressive Pon, most often causes S. pyogenes.

Bacterial Superantigen, showing the properties of polyclonal and simultaneously independent of the antimo-independent activators of the immune response, are able to bind immunoglobulins and activate in lymphocytes through their superficial immunoglobulin receptors. At the same time, the involvement in the activation process of autoreactive in lymphocytes, which in this case is the inevitable consequence of the total polyclonal activation of lymphocytes, is accompanied by a breakdown of autotoolelae, immune damage to cells and tissues, which can lead to clinical manifestations of the fact of autoimmune aggression.

The binding and subsequent neutralization of the biological activity of Superantigen are carried out mainly by proteins with the properties of natural and specific OpSonins. In this capacity, immunoglobulins and C-jet protein (CRP) are most active. The formation of the required amount of specific immunoglobulins requires considerable time, as it is implemented with an adaptive immune response. The total binding of non-specific immunoglobulins present in the circulation of non-specific immunoglobulins, therefore, only C-jet protein can play the main role in neutralizing the biological activity of spearntigen in the early stages of the shock reactions initiated by them.

Classic, or early "pro-inflammatory" cytokines (TNFA, IL-1BET) in excess concentrations due to system effects also participate in the formation of polyorgan dysfunction and can be considered mediators. As systemic should be regarded by the following effects of these cytokines:

• vasodilation accompanied by hypotension and the development of collaptic reactions;
• an increase in the permeability of the vessels with the extravasation of the plasma and the emergence of interstitial edema;
• coagulopathy consumption, focal syndrome and bleeding;
• disorders of the perfusion kidneys, liver, heart and lungs;
• hyperthermia as a result of the activation of the hypothalamus;
• hypoglycemia and the formation of the state of dysmetabolism of the brain;
• widespread activation of the endothelial cutting of blood vessels;
• significant body weight and development of cachexia.

The systemic effects of cytokines attributable to the family of tumor necrosis factors are leading in the pathogenesis of septic shock.

In the process of forming and deepening polyorganic disorders, the cells of various organs are dying as a result of direct damage to the factors of secondary alteration. Actually, the process of acute cell death is realized by necrobiosis mechanism: either hypoxic or free-radical. The cause of their death may also be the process of self-destruction - apoptosis.

Apoptosis is initiated by the damaging effects of insufficient intensity and / or is the result of the impact of regulatory factors for the initiation of apoptosis. With its and pon the strongest activators of the apoptosis of lymphocytes, and other cells are TNFA and glucocorticoids.

However, almost all cytokines, excessively produced by activated mononuclear cells with its, including interleukins and interferons, can be inductors of apoptosis of immunoreactive cells. Moreover, in cells of one type, one or another cytokine launches apoptosis, and in other cells it inhibits it. Thus, in acute damage to the lungs in the foci of neutrophilic inflammation in the spaces of the alveoli, such phenomena as the delay in the apoptosis of neutrophils and the simultaneous acceleration of apoptosis of epithelial cells are noted.

Cells also die from various cytotoxic effects carried out with the participation of immune factors - autofagocytosis and extracellular cytotoxicity, complement-dependent cytotoxicity, cytotoxicity, implemented by specialized killer cells - NK, LAK, CTL.

With the death of the cells, the necrociosis mechanism, as well as the implementation of the effector cells of the extracellular cytotoxicity, in the intercellular spaces in excess, hydrolytic enzymes are obtained by lycase - neutral and acid proteases, lipases, glycosidases, phospots. Lisosomal hydrolytic enzymes destroy the dead cells, but can also participate in damage to cytoplasmic membranes of normal cells and the intercellular substance of tissues.

Thus, there are numerous and distinguished by the direct damage mechanism of alteration options that are implemented with severe sepsis. These mechanisms carry out those pathological changes in molecular, sub-bottle, cellular and tissue levels, which, with their accumulation and generalization of the main processes, underlie the formation of pathological changes in many organs as the essence of phenomenon of polyorgan dysfunction.

Many of these factors and mechanisms have an immune nature. At the same time, the immune system, initially the system of integrative regulation and protection, turns into a contractor and at the same time sacrificing the same factors formed and it are also sacrificing the mechanisms for the implementation of the biological activity of these factors that come out from under control and become a source of damage to many organ systems. Naturally, such biological chaos cannot but affect the immune system itself, forming significant disorders of the structural-morphological organization in its links and violating the main functions.

The role of endothelial dysfunction with its own

The endothelial liner of the vessels of various organs in recent decades is no longer considered as an inert physical barrier separating blood from the subjectable fabric. There is no doubt that endothelium is a highly active morphofunctional system that has unique metabolism and is actively involved in many homeostasis processes, including blood maintenance mechanisms in a liquid state, control of the vasomotor tone, the mechanisms of carrying nutrients, the emigration of leukocyte blood cells in tissue, mononuclear nature recycling processes.

Endothelial cells (especially when activated by cytokines, biogenic amines, kinines and thrombin) express the rich gamut of molecules of intercellular interactions, and receptors for a set of cytokines. Endothelial cells are also distinguished by proagulant molecules - a Willebrand factor and a plasminogen activation activation inhibitor of type 1. In addition, endotheliocytes express receptors for fabric factor and thrombin, coagulation factors complexes, and also participate in the involvement of platelets and monocytes to the sections of the activated endothelium.

The role of endotheliocytes is large and in the implementation of anticoagulant processes. These cells are distinguished by heparin sulfate, prostacycline, thrombodulin, fabric activator plasminogen, a tissue factor inhibitor and endothelial inos, thereby counteract coagulopathy.

In the norm of the endothelium, it is capable of maintaining the balance of the hemostasis system when the dynamic and other functions of the microcirculatory segments of the vascular bed. When sepsis, endothelium is involved in the pathological process, activating coagulation and oppression of fibrinolysis. Activated endotheliocytes are also capable of being cells-producers of classical "pro-inflammatory" cytokines, which turns them into indispensable participants in a generalized inflammatory response.

Endotheliocytes "pro-inflammatory" cytokines, primarily TNFA, take the most active participation in processes associated with generalized inflammation forms. This predetermines the occurrence of organ dysfunction, and in the progression of sepsis and the development of septic shock - the formation of Pon.

In coagulopathy and disorders of fibrinolysis processes, the growing activation of a wide range of cells and endothelium of vessels with excessive products of classical "pro-inflammatory" cytokines, as well as other inflammatory mediators, is accompanied by the generalization of systemic inflammation by the type of "cytokine fire" with the early development of Pon.

Methodology for determining and interpretation of the development of its development

Clinically manifested by classic SIRS criteria. Additional (laboratory) diagnostic criteria are also defined: increasing the concentration of procalcitonin (\u003e 2 ng / ml), an increase in the level of inflammation protein-reactants (CRP, fibronectin and other proteins, adaptogens) and many cytokines, of which the greatest value Have IL-6 and IL-8.

On the initial stages In the structure of the main events of the pathogenesis, the infectious component may be absent, therefore, the genesis of this symptom complex may have a noncommunicable nature. The SMSMO symptoms are noted under traumatic damage to various etiology, with destructive pancreatitis, with severe ischemia of tissues of vital organs, with hemorrhagic shock, in the alteration of tissues with the participation of immune factors in the auto- and hypersensylization processes. Unlike sepsis, during its first 8-24 hours, the development of this reaction does not have growth in the blood plasma level of the commercial component.

The results of many years of practice of applying Sirs criteria for the purposes of clinical diagnostics of sepsis demonstrated the tendency of extended practices for diagnosing sepsis. That is why in 2001, clarifying definitions were adopted at the conciliation conference in Washington.

Extended sepsis diagnostics criteria

Infection in combination with the following changes

Key changes:

• Fever (sublingual temperature\u003e 38 ° C)
• Hypothermia (sublingual temperature< 36 °C)
• Heart rate\u003e 90 UD / min (\u003e 2 standard deviations from age norm)
• Tahipneoe
• Violation of consciousness
• Edems or the need to achieve a positive water balance (\u003e 20 ml / kg in 24 hours)
• Hyperglycemia (\u003e 7.7 mmol / l) in the absence of diabetes

Inflammatory changes:

• Leukocytosis\u003e 12 × 10x9 / l
• Lakeing< 4 × 10х9/л
• Cellular formula shift towards immature forms (\u003e 10%) with normal leukocyte content
• C-jet protein (magnification)\u003e
• ProCalcitonin (increase)\u003e 2 standard deviations from the norm

Hemodynamic changes:

• Arterial hypotension: adsist< 90 мм рт. ст., АДср < 70 мм. рт. ст.
• Reducing the adsist by more than 40 mm Hg. Art. (in adults)
• Reducing the adsist on 2 and more standard deviations from the age norm
• Saturation svo2\u003e 70%
• Cardiac index\u003e 3.5 l / min / m 2

Manifestations of organ dysfunction:

• Arterial hypoxemia - PAO2 / FIO2< 300
• Outragia Oligius< 0,5 мл/ (кг × ч)
• Increase creatinine by more than 44 μmol / l (0.5 mg%)
• Disruption of coagulation: APTU\u003e 60 s. or MN\u003e 1.5
• Thrombocytopenia< 100 × 109/л
• Hyperbilirubinemia\u003e 70 mmol / l
• Intestinal obstruction (no intestinal noise)

Tissue hypoperfusion indicators:

• Hyperlactatem\u003e 1 mmol / l
• Slow filling syndrome capillaries, marble limbs

Currently, it is recommended to diagnose the staging of the septic process, guided by these expanded criteria. Prior to the appearance of these criteria, the diagnosis of Sepsis was authorized in the presence of a focus of infection and two Sirs criteria. The diagnosis of "heavy sepsis" can be supplied in the establishment of signs of organ dysfunction (at least one by one organ), which is accompanied by a decrease in tissue perfusion.

Septic shock involves the presence of a hypotension with a duration of at least 1 hour; Reducing systolic blood pressure from its initial level by 40 and more MM RT. Art., or systolic hell< 90, или АДср < 60 мм рт. ст., когда отсутствуют другие причины гипотензии (например, гипотензия из- за приема медикаментов, гипотензия при инфаркте миокарда, кровопотере, травме).

In septic shock, hypotension is preserved under conditions of adequate infusion therapy, as well as after aqueous load with crystalloids (usually the mode of administration of crystalloid solutions at the rate of\u003e 20 ml / kg intravenously, inkjet). The statement of this state requires vasopressor support.

A sharp decrease in peripheral blood flow may indicate: increasing the level of lactate in the blood, oliguria or violation of consciousness. Other manifestations are possible. Patients receiving inotropic or vascular support may have signs of peripheral hypoperfusion in arterial pressure (AD), which has achieved as a result of normal level therapy.

Captively disturbed hemodynamics and rheological disorders lead to a sharp deficiency of oxygen in tissues, substrates of tissue respiration and nutrients. Tissue hypoxia progresses, basic metabolic processes are violated, acid-base equilibrium changes, acidosis increases. Septic shock with outcome in the DVS syndrome - the most frequent cause Few outings with severe sepsis.

Another deserving trend of diagnostics is reduced to attempts to develop integrative diagnostic algorithms based on a quantitative assessment of the contribution of the links of various pathological processes (and characterizing their indicators) in the development of the critical state of patients.

Prokalcitonin test

The dependence of the fact of increasing blood plasma concentrations of some calcitonin processes, primarily prokalcitonin (PCT), with the development of generalized forms of infection (including sepsis) and systemic inflammation (for example, with polytrauma, severe burns, destructive pancreatitis).

Some researchers consider procalcitonin with a specific infection marker and allow the use of a prokalcitonine test along with other molecular markers of its (C-reactive protein, IL-6, other cytokines) not only to monitor the development process and proceeding the generalized inflammatory response, but also for the diagnosis of sepsis as generalized infections, emphasizing the high sensitivity and specificity of this diagnostic criterion.

However, much still remains unknown. So, the role of procalcitonin in the pathogenesis of sepsis is not entirely understood, and why, during sepsis, many cells (regardless of their specialization in normal conditions) suddenly turn into active producers of this influencing the exchange of calcium with the protogormon. Probably the test on the level of procalcitonin is more useful for monitoring tasks, not the tasks of the formulation of the diagnosis. The use of this test cannot replace all other approaches and methods for diagnosing sepsis and its complications.

General (systemic) Immunodepression during sepsis

In the late stages of the septic process, the multifactorial immunosuppression in importance exceeds the activation role of its and largely predetermines the formation of late (infectious or septic), which is usually formed after the latent period of relative well-being and can be considered as a variant of classical secondary organ failure.

As well as its, general immunosuppression is a systemic pathological process. It is known that in the oppression of many structural components of the immune system, the overall immunosuppression increases and brings the immune system to complete functional insolvency.

The exacerbation of the concomitant sepsis of immune disorders turns out to be a consequence of several main reasons and is implemented in the cooperative interaction of the following processes. First, the number of cells needed to implement the adequate operation of immunity protective systems due to necrobiotic effects and in the intensification of the cells of the cells of the cells progressively decreases.

In particular, it is known that during sepsis sharply increases the intensity of the death of lymphocytes with the apoptosis mechanism. Changes in apoptosis processes are also described for monocytes and neutrophils (during sepsis, the intensity of the apoptosis of monocytes increases, and neutrophils decreases). Secondly, the dysfunction of the immune system turns out to be a consequence of regulatory (cytokine) and subpopulation (phenotypic) imbalance of cellular components and molecular factors of immunoreactivity. Thirdly, functional failure is developing - the aerygy of immunoreactivity cells both according to the features of recognition and presentation of antigens and according to other effector, as well as regulatory functions of these cells.

When sepsis about the presence of general immunosuppression, it is possible to judge clinical manifestations and data of laboratory research methods that evaluate the immune status of patients. Clinical signs of general immunosuppression: the increase in endo- (auto-) toxicosis, the occurrence of secondary septic foci or the development of visceral infectious complications.

Microbiological criteria for general immunosuppression: change of microbial landscape with a predominance of a conditionally pathogenic flora or with its consistent replacement of hospital strains. Laboratory and diagnostic criteria for general immunospression: pancytopenia, leukopenia, lymphopenia, increasing the leukocyte index of intoxication, an increase in the blood plasma concentration of medium mass peptides and "anti-inflammatory" cytokines, as well as other immunosuppressive factors (glucocorticoids, PGE2, TGFP1 (IL-LRA, IL- 4, IL-6, IL-10), a change in the ratio of concentrations of "pro-inflammatory" and "anti-inflammatory" cytokines (for example, to increase the values \u200b\u200bof the concentration relations in the blood plasma - IL-LRA / TNFOT, IF-10 / IFNY).

In terms of general immunosuppression, invasion of pathogens becomes uncontrollable. Heavy forms of immunosuppression are not independently compensated for, without adequate correction with drugs of the replacement type of action (immunoglobulins, recombinant cytokines / RIF-2, Rifny /, recombinant colonystimulating factors) has a consequence of escalation and other pathological processes to their fatal outcome.

Mechanisms for the development of general immunosuppression (including the role of various immunosuppressor factors) can be interrelated with a generalized inflammatory response (the so-called "compensatory anti-inflammatory response syndrome" - CARS), and can be formed regardless of the generalization of inflammation. A similar pattern is a consequence of the multicomponent nature of the pathogenesis of the general immunosuppression.

Heavy sepsis: polyorgan dysfunction and insufficiency. Modern criteria and diagnostic methodology

Heavy sepsis is sepsis, complicated by the development of polyorgan deficiency, which dramatically takes the clinical picture sharply and has an unfavorable forecast. Most often, severe sepsis develops with surgical diseases that require volumetric operations on the abdominal organs. Therefore, abdominal sepsis consider one of the most dangerous clinical forms of heavy sepsis.

Polyorgan deficiency (Mon)

In the formation of Pon, all organs and tissues of the body are affected. This lesion is a consequence of the effects of aggressive mediators and excessively activated cells, including cells using immune mechanisms of alteration potential. The mechanisms of damage to tissues are universal, as a rule, are deprived of fabric and organ specificity.

In the genesis of these universal defeats, the effects of free radicals that are able to initiate the processes of free-radical necrobiosis and apoptosis in the cells are significant. The role of excessive apoptosis of cells in initiating the damage to the vital organs in the patients in the critical condition can be very significant. The sequence of involvement in this process of organ systems is determined only by the temporary predominance of symptoms of one or another organ dysfunction - pulmonary, cardiac, renal or any other.

If the development of pathological processes is not compensated by protective-adaptive reactions, and the effects of primary and secondary alteration are summed up, the function of vital organs is violated and the mono-ordinal (more often pulmonary) is developing, and then polyorgan failure.

It is usually estimated by the criteria for polyorganized dysfunction syndrome (SPO mods / Multiple Organ Dysfunction Syndrome /). The manifestation of the signs of Pon means the formation of a qualitatively new and extremely dangerous for the life of a patient pathological state, because at the same time, dysfunctions of organs and systems in various versions occur and deepened. Next, the situation develops according to the scenario of an unmanaged systemic crisis, accompanied by disorders of integrative and target cytokine regulation, in the genesis of which the role of the immune system is obvious.

Consequently, Pon is a condition characterized by significant changes in the functions of several internal organs in heavy patients, the state of homeostasis cannot be supported without external intervention. The fatal outcome of both the early (or activation) pon and at the late (or septic) pon has a high degree of probability. Female outcome is also inevitable in the absence of adequate treatment.

Mortality in the formation of PO fluctuates from 35 to 75% or more. The mortality rate directly depends on the number of organ systems involved in the development of dysfunction. Involvement in the first organ system increases for the patient the risk of fatal outcome 2 times. Since in determining the level of mortality, the number of organic-functional systems involved in the formation of this pathological state of organo-functional systems, the timely identification of signs of organ dysfunction on all vital systems of the body is a fundamental question of diagnosis.

This dictates the need to further search for the diagnosis criteria for the signs of the regulatory integration system and individual organ-functional systems, including the immune system, as well as the development of the principles of the prevention of the Pon and modern strategy of advanced intensive therapy.

Patient survival markers with Pon

Some patient survival markers were revealed. These are usually referred to:

• lactate level in arterial blood;
• levels of bilirubin and creatinine in blood serum;
• the value of the oxygenation coefficient (PAO2 / FIIO2) is the main criterion for the degree of damage to the lungs.

Identification of the markers of the Pon on other authority systems and the definition of their prognostic value remains one of the most relevant diagnostic tasks. With all the sharpness there is a question about the need to include immune nature markers in the number of prince criteria. In this regard, such a undoubted criterion of insufficiency of the immune system, such as absolute lymphopia, deserves special attention.

In practice, the definition of the number of polynomials involved in the pathogenesis, as well as an assessment of the duration of the state of Pon in the patient, it is enough to accurately navigate in the likelihood of death. A. V. Rudnov (2000) cites the following data on mortality statistics among patients in critical condition. When setting in patients, the dysfunction of one system registered mortality at the level of 15%, two - 32%, three - 59.4%, four or more - 91.4%.

Thus, the formation of insufficiency of the next organ system with severe sepsis sharply increases the likelihood of death. Therefore, as a mandatory addition to the diagnosis of "Heavy Sepsis", it is necessary to describe organ dysfunction in the patient.

Diagnosis of severe sepsis

As already noted, sepsis (in the English-speaking medical literature - "sepsis-syndrome") is severe, in which the proceeding of the septic process is complicated by the development of polyorganian (polysystem) deficiency in a patient, therefore, the methodology for assessing the severity of Pon is the cornerstone in the diagnosis of severe sepsis.

According to the consolidated opinion of the majority of specialists, the severity of the PON should be assessed by the aggregate (the presence or absence of a specific indicator) MODS criteria (\u003d syndrome of polyorgan dysfunction - spod), the development of which was the result of several international conciliation conferences on this issue, over the past decade of the 20th century.

Generalized criteria for organ dysfunction

Dysfunction of the hemostasis system

• Coagulopathy consumption:
• fibrinogen degradation products\u003e 1/40
• dimers\u003e 2;
• protombian index< 70%;
• thrombocytes< 100 (с 2001 г.) - 150 × 10х9/л;
• fibrinogen< 2 г/л или динамические изменения: снижение тромбоцитов > 50%,
• increase in prothrombin time\u003e 20%;
• since 2001 - APTU\u003e 60 s.

Cardiovascular Dysfunction

• Systolic pressure< 90 мм рт. ст. или среднее давление < 70 мм рт. ст., некорригируемое возмещением жидкости в течение как минимум 1 ч (кристаллоиды 20–30 мл/кг за 30 мин + допамин ≥ 5 мкг/кг/мин);
• acidosis inexplicable causes (pH ≤ 7.3) or base deficiency ≥ 5.0 mmol / l + more than half-breasted in comparison with the rate of racking plasma level (\u003e 1mmol / l; since 2001)

Acute RDSV (As part of acute lung damage syndrome - nozzles)

• sharp start
• double-sided pulmonary infiltration (bilateral pulmonary infiltrates on the radiograph),
• pressure pressure of pulmonary artery< 18 мм рт. ст., необходимость ИВЛ с ПДКВ > 5 cm Waters. Art.,
• hypoxhemia refractable to oxygen therapy.
• The difference between the RDSV into the degree of hypoxemia, expressed in the form of RAO2 / FIO2 relationship: with RAO2 / FIO2 nozzles< 300, при РДСВ < 200 мм рт. ст.

Renal dysfunction

• Creatine blood\u003e 176 μmol / l, or an increase in creatinine\u003e 0.5 μmol / l (since 2001);
• sodium urine< 40 ммоль/л;
• teases temp< 0,5 мл/кг за 1 ч при адекватном восполнении ОЦК

Hepatic dysfunction

• Bilirubin Blood\u003e 70 μmol / l (since 2001),
• an increase in AST, Alt or alkaline phosphatase 2 times or more of the norm

CNS dysfunction

• < 15 баллов по шкале Глазго

Methodology of clinical assessment of the severity of Pon with severe sepsis

In clinical practice, various scores of estimates, which differ in the threshold values \u200b\u200bof physiological variables and by the number of parameters included, are also quite widely used. The presence of various techniques and preferences for their use in the practical activity of certain institutions are the result of the absence of a single and generally accepted estimate system.

Thus, the severity of the state of patients with Pon is estimated by the apache (I, II, III) scales using a simplified physiological scale (SAPS), according to the model of probable mortality (MRM), as well as on specific scores of organ dysfunctions (MODS - function disorders Several organs, Sofa - scale estimate scale of the function of organs during sepsis, LODS is a logical scale of estimating the disturbed functions of various organs).

The listed scales make it possible to evaluate the presence or absence of organ dysfunctions, as well as determine their degree on the principle of stepwise evaluation. Using them, it is possible to quantify not only the severity of the dysfunction of a particular organ-functional system, but also the severity of polyorgan (i.e., the body's dysfunction. These scales can also be used to predict the mortality of patients in the critical condition. The results of such an assessment quite accurately coincide with the actual mortality rates of patients, the severity of the clinical state of which was complicated by the development of Pon.

It should be emphasized that in modern systems for estimating polyorgan dysfunction there are no criteria that characterize the dysfunction of the immune system as a full organ-functional education (including in estimated scale there is no criteria for systemic immunosuppression).

Apache and SAPS evaluation systems are highly specific (90%) for a favorable outcome forecast, but less sensitive (50-70%) relative to the forecasting outcome. Moreover, these systems are acceptable to predict the outcome and comparative analysis of groups of patients, but are not very effective for evaluating the individual state of patients. That is why they are not recommended for prognostic evaluation in a particular patient and cannot be a routine basis for decision-making in clinical practice. This was noted at the conciliation conference of the European Society of Intensive Medicine in 1998.

The purpose of the use of methods for estimating polyorgan deficiency on MODS and Sofa scales is the other, namely a description of the organ dysfunction, and with individualization for a particular patient. Focused on estimating the dynamics of changes in the function of vital organs and methods of techniques (Sofa, MODS) make it possible to estimate the effectiveness of the treatment carried out, but their predictive possibilities of the probabilities of the fatal outcome and the development of complications are limited.

Russian conciliation conference (Moscow, October 2001) and the latest international conference of experts (Washington, December 2001) recommended for the assessment of the priesthood in patients with severe sepsis to use the Sofa scale.

Diagnostic value of the Sofa scale

Despite the minimum of the parameters to be evaluated, the Sofa scale (SEPSIS-Related Organ Failure Assessment) has a high diagnostic value. This scale can be used to evaluate with any critical states, and not only with severe sepsis.

Recently, the Sofa abbreviation is decrypted as "Sequential Organ Failure Assessment", emphasizing the ability to evaluate with this scale of the condition of heavy patients in the dynamics. Another estimated scale proposed by a group of Canadian specialists is very similar to the Sofa scale. When it is used, it is necessary to additionally measure the central venous pressure.

Based on the simple addition of points for each of the parameters given in the above-listed above, it is also possible to trace changes in the state of patients in dynamics and during treatment.

Septic shock: Clinic, Pathogenesis, Differential Diagnosis

The state of the shock in septic patients is developing due to inadequate perfusion of internal organs, which is a consequence of acute circulatory failure. Violation of blood supply to tissues is accompanied by the development of tissue hypoxia. In this state, even intensively conducted infusion therapy is not able to maintain hell above the critical level, and constant administration of vasopressar drugs is required.

Pathogenesis and clinical characteristics of septic shock. The basis of hemodynamic disorders developing under septic shock are not so much violation of the central mechanisms of vasomotor regulation, which is characteristic of traumatic shock, how many changes in the peripheral microcirculation system.

Clinically, the development of shock is characterized by a sharp drop of blood pressure, tachycardia, a pulse of a weak filling, a cold later, shortness of breath, oliguria. These signs quickly progress. The fact of the development of shock is confirmed by a decrease in hematocrit. The prediction during septic shock is often fatal, especially with the development of the DVS syndrome. His accession is always a disaster, as the loss of fluid properties with blood, as well as the violation of its circulation in capillaries is not compatible with life.

The development of the DVS syndrome marks the patient's entry into the decompensated phase of shock. Capturally disturbed hemodynamics and hemorrheal disorders lead to a sharp deficiency of oxygen in tissues, tissue respiratory substances and nutrients. Tissue hypoxia progresses, basic metabolic processes are violated, acid-base equilibrium changes, acidosis increases. Septic shock with outcome in the DVS syndrome is the most common cause of death in sepsis.

Properly allocating the following four key signs of septic shock:

• clinical evidence of the presence of infection;
• signs of CBSME (\u003e 2 sirs-criteria);
• arterial hypotension, not compensated by infusion, or the need for permanent use of vazopressors to maintain blood pressure at the level of critical;
• clinical and laboratory signs (indicators) of organic hypoperfusion.

The diagnosis of "Septic shock" is justified if there are all without exception of these signs. However, for the correct formulation of the diagnosis, the following are: the fact of preceding infection and the presence of its criteria. Other reasons for hypotension that should be excluded include: the reception of the relevant medicines, an extensive myocardial infarction, massive blood loss and severe traumatic damage to organs and tissues.

A sharp disruption of blood supply to tissues and increasing tissue hypoxia form progressive polyorgan deficiency with multiple lesions of organs. First of all, the respiratory distress syndrome of adults (RDSV) and acute renal failure are developing.

For septic shock, the perversion of blood coagulation is also characteristic, which leads to multiple hemorrhages, including with organic localization. Septic shock and organ dysfunction are regarded as the patient's weighting state stadium complications of sepsis, which have a forecast extremely unfavorable for his life.

In blood circulation disorders, several phases are usually traced during septic shock. In the initial - hyperkinetic phase, the total peripheral resistance of vessels is reduced. At the same time, the values \u200b\u200bof heart emissions are normal or even somewhat enlarged, arterial and venous pressure is sharply reduced. Over the next, the hypokinetic phase is reduced both peripheral resistance and cardiac output values. In the last - terminal phase, phenomena of heart failure increase, hypoxia, acidosis and impaired water-salt balance are progress.

Generalized infectious complications in patients with surgical profile can clinically immediately flow as septic shock. This is possible when the virulent pathogens are massive in total bloodstream, bypassing the natural barriers to the non-specific resistance of macroorganism. Such clinical manifestation may also be observed with a traumatic endo- (auto-) toxicosis and in the case of the mass death of gram-negative pathogens with the release of large amounts of bacterial lipopolysaccharide, which performs the functions of endotoxin with a powerful hypotensive effect. If the infection develops in the patient in the critical state, and there are systemic disorders of microcirculation, then sepsis can immediately proceed as heavy, and septic shock is possible.

Features of the diagnosis of septic shock and lightning

Despite the introduction of ideas about the stadium development of the infectious process during sepsis, the traditional division of sepsis on the lightning, acute and subacute preserves undoubted clinical attractiveness, as it allows you to formulate a real forecast for the development of the clinical situation and correctly choose the therapeutic tactics. In the light of the modern concept, its sepsis include lightning and sharp clinical forms in old terminology. The principles of the diagnosis of septic shock and sepsis, clinically flowing lightning, differ significantly from the methods of diagnosing other forms of sepsis.

The diagnosis of gravity of the septic state is adequate when it is primarily based on the clinical picture. This is explained, on the one hand, the presence of clear clinical symptoms, on which you can track the severity of patients, and on the other - the need to diagnose these types of sepsis and begin treatment no later than the first 6-8 hours from the appearance of clinical signs, otherwise the effectiveness of therapeutic measures Reductantly decreases.

Both forms may occur at any stage of the infectious process. In this case, the orientation of the formal signs of septic shock, proposed by R. Bone (1991): "Septic shock" \u003d CBE + PON + hypotension or "heavy sepsis" + hypotension, may be insufficient for several reasons. First, these signs often coincide for both (lightning and acute) forms of the infectious process, secondly, due to the rapid development of the set of pathological reactions, they are difficult to catch and, thirdly, may appear against the background of the relative well-being of the patient's clinical state without Preceded by the impending catastrophe of signs of sepsis.

Differential diagnosis of endotoxic shock and toxic shock syndrome

S. A. Rozhkov et al. It is right that the differential diagnosis of septic (endotoxic) shock and toxic shock syndrome caused by gram-positive microorganisms is absolutely necessary, since some directions are adequate pathogenetic therapy With these states are opposite.

The development of septic (endotoxic, infectious-toxic) shock is manifested by a picture of the primary microcirculation disorder, which can be estimated as a state of both peripheral and central blood circulation. The following symptoms are characterized: skin marble, collaptic stains, drop blood pressure, threaded disappearing pulse, clean and clear (often loud) heart tones. Originally high body temperature quickly drops to normal. The psychic condition of the patients is characterized by euphoria, which is then replaced by injecting.

Some authors this condition is denoted as a lightning gram-negative (meningococcal, salinellase, echerychoid, pseudomonade) sepsis. The etiological factor of septic shock is, as a rule, gram-negative microbes. However, in the conditions of a long existence of an extensive purulent focus, the clinical picture of the septic shock may not depend on the type of pathogen defined in the hemoculture.

The shock of infectious nature can develop and without sepsis with bacterial (abdominal typhoid) or viral (flu, hemorrhagic fever) infections, as well as due to the one-time admission to the body of a large number of bacterial exotoxins (intestinal toxicoin intake) - toxic shock in infections. For example, a similar shock can be induced by enterotoxin E and diphtheria toxin. In these cases, the shock is due to both microbial (toxin of toxic shock 1, enterotoxin f) toxins of grapple microorganisms and autolysis products of damaged cells and tissues, which run a complex cascade of cytotoxic immune reactions with preferably damage to the endothelium of vessels.

Golden Staphylococcus - frequent, but not the only cause of toxic shock syndrome. Similar systemic reactions may be due to S. pyogenes infection and coagulazo-negative staphylococci, producing exotoxins with the properties of Superantigen. Circulatory disorders increasing when exposed to these factors lead to a secondary increase in the permeability of the intestinal barrier and to the additional entry into the overall blood flow of endotoxins from the gastrointestinal tract. In surgical practice, the development of toxic shock syndrome is most often associated with wound infections, postoperative complications, mastitis, postpartum endometritis.

The main link of pathogenesis of both endotoxic septic shock and toxic shock syndrome is a negative impact on microcirculation of bacterial toxins. Therefore, without eliminating the effects of the etiological factor, with the help of only effective etiotropic therapy, it is impossible to achieve positive shifts in the state of patients, even intensively carrying out anti-deposit measures. With septic shock, the impact on the processes of microcirculation pathogenetically absolutely justified, but in practice this leads only to temporary improvements to the clinical situation.

The main link of the pathogenesis of the lightning sepsis, whose causative agent is more likely to be the grampositive (usually staphylococcus) microflora, is the primary heart damage and the drop in its contractility (primary violation of central hemodynamics) caused by the effects of staphylococcal exotoxin, which acts as cardiotropic intoxicant.

For lightning sepsis, the following triad of clinical symptoms is characteristic:

• sharp body temperature up to 39-41 ° C;
• early development of acute left left vessels (cardiac asthma, pulmonary edema, the expansion of the heart boundaries, deafness of cardiac tones);
• fear of death.

The tactics of treatment of patients with lightning room (gram-positive, usually staphylococcal) sepsis should be eliminated by heart failure and the immediate conduct of non-specific and specific detoxification measures (neutralization) of staphylococcal exotoxins.

Conclusion

In sepsis of any genesis, the development of the septic process begins with the appearance and sharp increase in the concentration in the systemic circulation of bacterial and mycotic antigens, at the same time being virulence factors with the properties of the activators of plasma systems of cascade proteolysis and immunoreactivity cells capable of producing "Provo

global »Cytokines and other inflammation mediators. The consequence of these processes is the development of a generalized form of an inadequate response of the body to an infection - a systemic inflammatory response.

Further, the situation is developing according to the scenario of an unmanaged systemic crisis, accompanied by disorders of integrative and target cytokine regulation, in the genesis of which the role of the immune system is obvious. Polyorgan Dysfunction is sharply or gradually formed, and in extreme forms - polyorgan deficiency (PON), a manifested combination of relevant clinical and laboratory signs - polyorgan dysfunction syndrome (SPO).

Currently, algorithms for assessing the severity of Pon, algorithms for assessing the severity of patients according to various scales, algorithms for predicting the outcome of severe sepsis are proposed. However, the fatal outcome is still a fatal case as with early (or activated) mon and at the late (or septic) pon, it has an extremely high degree of probability, which dictates the need to further search for the criteria for the diagnosis of Pon, on signs of the dysfunction of the regulatory integration system, as well as individual organotofunctional systems. , including the immune system.

Pronounced immune disorders, including depression disorders, were noted already during the early Pon, and in the formation of septic Pon, it becomes defining that it sets the question of the eligibility of the interpretation of sepsis as an activation immune dysfuction - its.

The dysfunction criteria of the imminent system of the opposite direction, in particular, such a form as a general immunosuppression, according to informativeness should not be given by other criteria for dysfunctions of other organo-functional systems, so weighted assessment of the possibility of their use as likely informative features of Pon. Successes in this direction can be plenty of milestones in the fight against sepsis.

At the heart of successful tactics in the treatment of sepsis of any genesis lies the greatest diagnosis of the septic state. In achieving ultimate success of efforts to save patients who have a high chance to die from sepsis, the identification and active surgical treatment of primary and / or secondary purulent foci is equally important, as well as the leading and most importantly - adequate ethiopathogenetic therapy using effective antibiotics and drugs replacement immunocorrection on life indications for any manifestations of immunosuppression.

Diagnosis and treatment of heavy sepsis

And septic shock

chaired by Academician

Diagnostic criteria of sepsis

Infection, alleged or confirmed in combination with several of the following criteria:

General criteria

Hypertermia, Temperature\u003e 38.3 ° C

Hypothermia, temperature<36oC

Heart rate\u003e 90 / min (\u003e 2 standard deviations from a normal age range)

Tahipneoe

Violation of consciousness

The need for infusion support (\u003e 20 ml / kg in 24 hours)

Hyperglycemia (\u003e 7.7 mmol / l) in the absence of diabetes

Criteria inflammation

Leukocytosis\u003e 12'109 / l

Lakeing< 4´109/л

Shift towards immature forms (\u003e 10%) with normal leukocyte content

Hemodynamic criteria

Arterial hypotension: adsist<90 мм. рт. ст., АДсра <70 мм. рт. ст., или снижение АДсист более, чем на 40 мм. рт. ст. (у взрослых) или снижение АДсист как минимум на 2 стандартных отклонения ниже возрастной нормы.

Saturation svo2\u003e 70%

Cardiac index\u003e 3.5 l / min / m2

Criteria organ dysfunction

Arterial hypoxemia PAO2 / FIO2<300

Outragia Oligius<0,5 мл/кг ´час

Increase creatinine by more than 44 μmol / l (0.5 mg%).

Coagulation Violations: APPB\u003e 60 sec. or MINOS\u003e 1.5

Thrombocytopenia< 100´109/л

Hyperbilirubinemia\u003e 70 mmol / l

Pares of intestines (no intestinal noise)

Indicators of fabric hypoperfusion

Hyperlactatem\u003e 1 mmol / l

Symptom of slow filling of capillaries, the marble of the limbs

Note: ADSIST is systolic blood pressure, ADSR is a secondary blood pressure. ; Baptwe - activated partial thromboplastinetime; Arranged normalized relationship

Classification of sepsis

Pathological process

Clinical laboratory signs

System inflammatory response syndrome - systemic reaction of the body on the impact of various strong stimuli (infection, injury, operation, etc.)

It is characterized by two or more of the following features:
- temperature ³38Os or £ 36 ° C
- CSS ³90 / min
- CH\u003e 20 / min or hyperventilation (Raso2 £ 32mm. RT. Art.)
- blood leukocytes\u003e 12'109 / ml or
<4´109/мл, или незрелых форм >10%

Sepsis - syndrome of the system inflammatory response to invasion of microorganisms

The presence of a focus of infection and 2 or more signs of a systemic inflammatory response syndrome

Heavy sepsis

Septice, combined with organ dysfunction, hypotension, disorders of tissue perfusion. The manifestation of the latter, in particular, is to increase the concentration of lactate, Oliguria, an acute violation of consciousness

Septic shock

Sepsis with signs of tissue and organic hypoperfusion, and arterial hypotension, not eliminating with the help of infusion therapy and requiring the appointment of catecholamines

Additional definitions

Polyorgan Dysfunction syndrome

Dysfunction 2 or more organs

Refractory septic shock

Preserving arterial hypotension, despite adequate infusion, the use of inotropic and vasopressor support

Criteria for organ dysfunction with severe sepsis

System organs

Clinical and laboratory criteria

The cardiovascular system

Systolic blood pressure ≤90 mm Hg or average blood pressure ≤ 70 mm HG for at least 1 hour, despite hypovolemia correction

urinary system

Diuresis< 0,5 мл/кг/ч в течение 1 часа при адекватном волемическом восполнении или повышение уровня креатинина в два раза от нормального значения

Respiratory system

Respiratory index (PAO2 / FIO2) ≤ 250 mmHg or the presence of bilateral infiltrates on the radiograph or the need for ventilation

Increasing the content of bilirubin above 20 μmol / l for 2 days or raising the level of transaminas twice or more from the norm

Cutting system

Number of thrombocyte< 100.000 мм3 или их снижение на 50% от наивысшего значения в течение 3-х дней

Metabolic dysfunction

Base deficit ≥ 5.0 meq / l

Plasma lactate 1.5 times higher than the norm

Glasgow score score less than 15

Scale Sofa (Sequential Organ Failure Assessment)

It is used for daily assessment of the patient's condition and evaluating the effectiveness of therapy.

Indicator

Oxygenation

mm RT. Art.

Cordially-

Vascular

Average hell

mm RT. Art.

or vasopressors,

μg / kg / min

Dopamine< 5

or Dobutamine

Dopamine 5-15

or Noraderenalin

Dopamine\u003e 15.

or Noraderenalin

Coagulation

Platelets

Bilirubin,

Creatine

Glasgow scale

The practical significance of the definition of the concentration of procalcitonin during sepsis

l Differential diagnosis of sterile infected pancreatic (PCT \u003d FNA, but in real time)

l Determination of readings to relamarotomy (when conducting patients in "on demand" mode)

l Differential diagnosis of "pseudoSepsis" and fury syndrome Unclear genesis

l Differential diagnosis of infectious and noncommunicable ORDS

l Determination of indications for high-cost treatment methods (antibiotics, extracorporeal methods)

l Including criterion when conducting tests of new methods of treatment

1. Surgical treatment of sepsis

Effective intensive sepsis therapy is possible only under the condition of a full surgical sanitation of the focus of infection and adequate antimicrobial therapy. Surgical treatment should be directed to an adequate rehabilitation of purulent-inflammatory foci. The methods of surgical intervention include:

1. Drainage of purulent cavities

2. Removing foci of infected necrosis

3. Removal of internal sources of contamination - colonized implants (artificial valves of heart, vascular or artificial prostheses), foreign bodies, temporarily with therapeutic goal of the body embedded in tissue or internal environment (tubular drainage and catheters), as well as removal or proximal shutdown (lead) The content of the contents of the defects of the hollow organs considered as sources of infection.

with an unspecified primary hearth

Conditions of occurrence

Tools of the 1st Row

Alternative means

developed

complete community

conditions

Amoxicillin / Clawulanate

+/- aminoglycoside

Ampicillin / Sulbaktam

+/- aminoglycoside

Ceftriaxone +/-

metronidazole.

Cefotaxim +/-

metronidazole.

Ciprofloxacin +/-

metronidazole.

Offloxacin +/-

metronidazole.

Ploksacin +/-

metronidazole.

Levofloxacin +/-

metronidazole.

Moxifloxacin

developed

conditions

hospital

Apache II.< 15,

Cefepim +/-

metronidazole.

Cefoperazazon / Sulbaktam

Imipenem

Meropem

Ceftazidim +/-

metronidazole.

Ciprofloxacin +/-

metronidazole.

developed

conditions

hospital

Apache II\u003e 15,

and / or p

Have

Meropem

Ceftazidim +/-

metronidazole.

Cefoperazazon / Sulbaktam

Ciprofloxacin +/-

metronidazole.

3. Early targeted therapy

4. Vasopressors and inotropic support

The beginning of vasopressor therapy is possible only in the absence of an effect on the bulk load (FVR 8-12 MMHG). Preparations of choice - dopamine and (or) Noradrenaline (Meston). Selection of doses is carried out before the reduction of adequate organ perfusion (ADSR\u003e 65 MMHG, diuresis\u003e 0.5 ml / kg / h). It is impractical to the appointment of dopamine in the "renal" dose. In the case of inadequate cardiac index (SVO2< 70%, гиперлактатемия) необходимо добавление к терапии добутамина. В случае рефрактерного септического шока при адекватной объемной нагрузке и высоких дозах вазопрессоров возможно подключение вазопрессина в дозе 0.01-0.04 МЕ/мин.

Respiratory therapy

· Respiring volume 6 ml / kg of perfect body weight

· Pressure pressure< 30 см вод. ст.

· Optimal PDKV (usually 10-15 cm water. Art.)

· Application of maneuvers Opening Alveol ("Recruitment")

· Preferential use of auxiliary regimes

6. Corticosteroids

· Use of hydrocortisone in doses of 240-300 mg / day for 5-7 days in complex therapy of septic shock allows you to accelerate the stabilization of hemodynamics, abolition of vascular support and reduce mortality in patients with accompanying adrenal insufficiency (according to ACTG test).

· In the absence of the possibility of carrying out ACTG tests, it is resorted to the empirical purpose of the hydrocortisone in the specified doses.

7. Glycemia control

It is necessary to strive to maintain the level of glycemia within 4.5-6.1 mmol / l. At the level of glycemia, more than 6.1 mmol / l should be carried out insulin infusion (at a dose of 0.5-1 me / h) to maintain normoglycemia. Control of glucose concentration - every 1-4 hours depending on the clinical situation.

8. Activated Protein C (Sigritis)

· Introduction APS (drothopochin alpha activated, zigris) in the dosage of 24 μg / kg / min

for 96 hours reduces the risk of fatal outcome.

· Indications - sepsis with the severity of the state of more than 25 points on the Apache II scale

or the development of two-component polyorgan deficiency.

9. Intravenous immunoglobulins

The use of intravenous immunoglobulins within immunocyalheavy sepsis and septic shock therapy is currently the only proven immocorrection method for sepsis that increases survival. The best effect is registered when using a combination of IgG and IgM "Pentaglobin" at a dose of 3-5 ml / kg / day for 3 days in a row. Optimal results when using immunoglobulins were obtained in the early phase of shock ("warm shock") and in patients with severe sepsis and the range of gravity in the Arasne-II -20-25 points.

10. Prevention of deep veins thrombosis

· Use of heparins in preventive doses makes it possible to reduce mortality in patients with severe sepsis and septic shock.

· For this purpose, both unfractionated heparin and low molecular weight heparin can be applied.

· The efficiency and safety of low molecular weight heparins is higher than unfractionated.

11. Prevention of the stress-ulcer of the gastrointestinal tract

· The frequency of the occurrence of stress-yazv reaches 52.8%.

· Preventive use of H2 receptor blockers and proton inhibitors

pomp 2 and more times reduce the risk of complications.

· The main direction of prevention and treatment is to maintain pH above 3.5 (up to 6.0).

· An important role in the prevention of education stress-ulcer plays enteral nutrition.

12. Extracorporal detoxification

· The use of renal renal therapy is shown in the development of acute renal failure within the framework of polyorgan deficiency.

· It is possible to use continued and intermitting procedures

· Continued venous hemo (dia) filtering is preferable to hemodynamically unstable patients and patients with a brain swelling clinic.

· It is possible to use high-volume procedures in septic shock for the purpose of pathogenetic therapy.

13. Nutritive support

· Energy value - 25 - 35 kcal / kg / 24 hour - acute phase

· Energy value - 35 - 50 kcal / kg / 24 hour - phase of stable hypermetabolism;

· Glucose -< 6 г/кг/24 час;

· Lipids - 0.5 - 1 g / kg / 24 hours;

· Proteins - 1.2 - 2.0 g / kg / 24 hour (0.20 - 0.35 g of nitrogen / kg / 24 hours), careful control over a nitrogen balance;

· Electrolytes - Na +, K +, Ca2, respectively, balance sheet calculations and concentration in plasma + p2 (\u003e 16 mmol / 24 hours) + Mg2 (\u003e 200 mg / 24 hours)

· Early start of nutritional support in terms of 24-36 hours

· Early enteral nutrition is considered as a cheaper alternative to full parenteral nutrition.

· The choice of the method of nutritional support depends on the degree of severity of nutritional failure and the state of the gastrointestinal tract functions: oral administration of enteral diets, enteral proteid food, parenteral nutrition, parenteral + enteral probe food.

Literature:

1. Sepsis at the beginning of the XXI century. Classification, clinical and diagnostic concept and treatment. Patol-anatomical diagnostics.: Practical guide. - M.: Publishing house NTSSSH them, 2004. - 130 s.

2. Guide to surgical infections / ed. . - St. Petersburg: "Peter", 2003. - 853 p.

3. Delinger RP, CARLET JM, Masur H et al. Surviving Sepsis Campaign Guidelines for Management of Severe Seppsis and Septic Shock. CRIT CARE MED 32: 858-871, 2004.

Pathological process	Clinical laboratory signs
SSMO -She system reaction to the impact of various strong stimuli (infect, injury, operation, etc.)	Temperature of the body\u003e 38 ° C or< 36 °С; ЧСС > 90 m.; CH\u003e 20 per minute; blood leukocytes\u003e 12.0 ∙ 10 9 / l or< 4,0 ∙ 10 9 /л, или более 10% незрелых форм
Sepsis	There is no doubt if there are 3 criteria: 1) an infectious focus determining the nature of the pathological process; 2) CBSME (criteria for penetrating mediators of inflammation into systemic circulation); 3) signs of organosystem dysfunction (the criterion for the propagation of an infectious-inflammatory response beyond the primary focus). The presence of organ dysfunction is judged by the following clinical and laboratory signs (classification of R. Bone et al., Corrected and supplemented), and for the diagnosis of one of the listed criteria: but. Dysfunction in the hemostasis system (consumption coagulopathy): - Fibrinogen degradation products\u003e 1/40; - D-dimers\u003e 2; - PH< 70%; - тромбоцитов <150∙ 10 12 /л; - фибриноген < 2 г/л. b. Violation of the gas exchange function of lungs: - R A O 2< 71 мм рт.ст. (исключая лиц с хроническими заболеваниями лёгких); - билатеральные легочные инфильтраты на рентгенограмме; - Р а О 2 / FiO 2 < 300; - необходимость ИВЛ с положительным давлением конца выдоха > 5 cm Water.st. in. Renal dysfunction: - blood creatine\u003e 0.176 mmol / l; - Sodium urine< 40 ммоль/л; - темп диуреза < 30 мл/ч. liver dysfunction: - blood bilirubin\u003e 34 μmol / l; - an increase in the level of AST, Alt or alkaline phosphatase 2 times or more of the norm. d dysfunction CNS: - Less than 15 points on the Glasgow scale. e. Gastrointestinal insufficiency: - bleeding from sharp ulcers ("stress-ulcers") stomach; - Ileus durability of more than 3 days.; - diarrhea (liquid stools more than 4 times a day).
Heavy sepsis	Sepsis with signs of tissue and organic hypoperfusion and arterial hypotension (reduction of systolic blood pressure to the level< 90 мм рт.ст., которая устраняется с помощью инфузионной терапии.
Septic shock	Heavy sepsis requiring to correct arterial hypotension to use inotropic drugs
Sepsis with Pon	Sepsis with dysfunction 2 systems and more

Unlike bloodstures during sepsis and OGP, hypovolemia and the loss of NOCs are secondary due to two main reasons. One - plasma leakage, which occurs against the background of endothelium damage due to endotoxicosis and DVS syndrome, characteristic of the organism's general pollutory reaction, the other is a violation of the recycling of digestive juices and the formation of the so-called "third space", which is explained by endotoxicosis and abdominal ischemia, The queue leads to an increase in intestinal translocation. Therefore, the conduct of an anti-inflammatory complex ITM is beginning with crystalloid solutions. The use of protein blood products due to leakage from the vascular channel will increase the blockade an interstice, since together with proteins accumulates the water associated with them. From the interstice of protein and "bound" water can be removed only by lymphatic tissue drainage, and this process is slow, and it is broken by increasing urban pressure. The "free" water of crystalloid solutions is able to leave the interstitial space much faster, since it is unhindered by reabsorption into the vascular bed. In addition, from the Starling equation, describing the transcapillary fluid exchange, follows:

SCD \u003d code pl + p TK - TK code,

where the CCD is the midcapillary blood pressure, the code PL - the colloid-oncotic pressure of the plasma, P TK is a hydrostatic intricate pressure, the code of the TC is colloid-oncotic urban pressure.

This means that an increase in RTK will be able to increase the CCC (together with it - the venous return of blood to the heart and blood pressure) only if the codec does not increase. Therefore, the basis of infusion therapy to the restoration of the NOC, the liquidation of KHS-syndrome and oxygen debt should be solutions of crystalloids, and the use of protein preparations turns out to be dangerous. After stabilization of the NOC and with residual hypoproteinemia, for correction, the Code of PL is advisable to use the metered ICK infusion (10%) at a speed of 80-100 ml / hour. After surgical rehabilitation, reducing endotoxicosis, the use of protein preparations is less dangerous.

Medical program:

1. Urgent hospitalization in the IUIT.

2. Catheterization of the central vein.

3. Introduction of crystalloids or colloids to target values:

FLOLD 8 - 12 mm Hg. (12 - 15 mm Hg at IVL);

Garden\u003e 65 mm Hg;

Diuresis 0.5 ml / kg / h;

Saturation of mixed venous blood ≥ 65%.

4. Erythromasse transfusion to HT\u003e 30% to achieve saturation mixed venous blood ≥ 65%.

5. Maintain the garden\u003e 65 mm Hg. Dopamine or Noraderenlin.

6. Immediate start of starting antibiotic therapy with preliminary fence materials for bacteriological research:

Get hemoculture from peripheral blood;

One culture from each vascular catheter installed\u003e 48 hours ago;

Cultures from other sections under clinical indications.

7. Start intravenous administration Antibiotics as early as possible, in the first hour after the recognition of severe sepsis.

8. Perform the appropriate interventions to eliminate the focus of infection, remove potentially infected vascular catheters.

9. Ensuring the ventilation of the lungs (control over the patency of the respiratory tract, the use of oxygen 4-6 l / min. Through the nasal catheters or roton-axis mask, IVL with sepsis-induced nozzles / Ords).

10. Corticosteroids - hydrocortisone up to 300 mg / day. With a preserving hypotension.

11. Extracorporeal detoxification methods.

12. Enteral and parenteral nutrition with glycemia<8,3 мМоль/л.

13. Prevention of stress-ulcers H 2-blocks or proton pump inhibitors (inhibitors H 2 -receptors are preferred agents).

Considering the lack of currently developed unified scientific the reasonable theory of sepsiswhich would allow to systematize this disease, a pragmatic decision was made to achieve an agreed descriptive definition of sepsis for the purpose of its uniform assessment that opens up the possibility of epidemiological, microbiological, clinical and other studies aimed at improving diagnosis and treatment.

According to the proposal of the Joint Conference of Thoracic Society and Specialists in Intensive Therapy of the United States, septic shock It should be considered a condition of severe sepsis (uncontrolled infectious process + generalized inflammatory response + polyorgan dysfunction / failure), accompanied by hypotension (systolic blood pressure< 90 мм рт. ст. или его снижение на 40 мм рт. ст. и более от исходного), несмотря на адекватную инфузионную поддержку, наряду с присутствием признаков снижения периферического кровотока, которые могут сопровождаться повышением уровня лактата крови, олигурией или нарушением сознания, но не ограничиваться ими.

Patients receiving preparations, increasing the contractile ability of the heart (into) or vascular tone (stimulating a- and dopaminergic receptors), may have signs of peripheral hypoperfusion with normal blood pressure.

Thus, you can select four key signs development of septic shock (SS):
- clinical or laboratory confirmation of infection:
discharge of bacteria from blood, sterile cavities (pleural and abdominal cavities, subarachnoid space, cavity of the joint) or inflammatory foci in the tissues;
clinical manifestations of infection (for example, hollow organ perforation);
Additional signs of infectious disease (increased amount of leukocytes in exudates from sterile cavities, signs of pneumonia on the radiographs of the lungs, etc.);

Signs of generalized inflammatory response (GVR):
body temperature above 38 ° C or below 36 s;
Tachycardia is over 90 per minute;
Dyspnea more than 20 per minute, or Raso2 (carbon dioxide voltage in arterial blood) 32 mm RT. Art. and less or the need for IVL;
Leukocytosis of more than 12 * 10 9 / l or less than 4 * 10 9 / l or the number of young forms of leukocytes more than 10%.

- arterial hypotensionnot eliminated by adequate in terms of infusion, or the need to use vasopressors (see earlier);

- clinical and laboratory signs of organic hypoperfusion:
Violation of consciousness less than 14 points on the Glasgow scale (assesses the amount of three types of points in points: opening the eye, motor activity and speech response). With independent opening of the eyes, the ability to adequate motor activity, the normal speech contact is an estimate of 15 points. Violation of at least one of these types of activity leads to an appropriate decrease in the assessment;
Hypotension: Hell + 90 mm Hg. Art., either a decrease of more than 40 mm Hg. Art. Below the normal individual level, or the mean ± ± 70 mm HGF. Art. (more than 1 h);
Respiratory Distress Syndrome: Acute Beginning, Bilateral Infiltrates on the Radiograph of Lungs, RAO2< 70 мм рт. ст. при инсуфляции дыхательной смеси с концентрацией кислорода (FiО2) более 40 %, снижении величины дыхательного коэффициента (PaО2/FiО2 нормальное значение более 300) ниже 200; давление заклинивания легочной артерии (определяется в легочной артерии прямым методом с помощью катетера типа Сван-Ганса) менее 18 мм рт. ст. в отсутствие признаков перегрузки левого желудочка (необходимо исключить инфаркт миокарда и тромбоэмболию легочной артерии как причину перегрузки левого желудочка);
Sultuous lung damage: respiratory frequency less than 5 or more than 50 per minute; Conducting IVL more than 3 days; The need for insufflation of the respiratory mixture with an increased oxygen content (Fi02\u003e 40%), the need to use respiratory support (IVL) with increased positive pressure at the end of the exhalation (PDKV) more than 5 cm. st.;
Acute renal failure: serum creatinine level of more than 280 mmol / l or need for gemofiltration;
Acute hepatic insufficiency: jaundice, level of general bilirubin in the blood of more than 51 μmol / l or twofold increase in Alt, signs of hepatic encephalopathy;
Thrombohemorrhagic syndrome: reduction in platelets by 50% or more of the initial level; an increase in prothrombin time or activated partial thromboplastin time by 20% or more; Increasing the concentration of fibrinogen degradation products by 20%, the appearance of D-dimers at a concentration of 1:40 or more than 500 ng / ml.

Applied to children The following criteria (SS) were proposed:
- Two-time registration of the arterial hypotension (reduction of systolic blood pressure by more than 1/3 of the age norm), or
- the need to appoint vasopressors (with the exception of patients receiving dopamine at a dose of less than 5 μg / kg per minute), or - the presence of one and more signs of severe sepsis.

Signs of severe sepsis in children Includes the presence of a generalized inflammatory response syndrome in combination with neurological disorders (the score on the scale of the Glasgow's scale is less than 14 points) or with an increase in the level of lactate in the blood of more than 1.6 mmol / l), or with a decrease in diurus (less than 1 ml / (kg * h) For 2 hours). Assessment of the frequency of respiration and heart abbreviations for the diagnosis of generalized inflammation is carried out on the basis of the boundaries of the age norm.

Clarifications are made to the terminology and diagnosis criteria sepsis, septic shock criteria (SS) for children and newborns. Given the fact that arterial hypotension in children is developing late and is a manifestation of decompensated shock, as a fundamental shock criteria, it is considered to consider clinical signs of a decrease in peripheral perfusion (reducing the level of consciousness, cold and cyanotic limbs, the symptom of the "white spot" with a duration of more than 2 s, a decrease Diurea).