Septic shock in urological diseases

Septic shock (bacteriotoxic shock, bacterial shock, toxic-infectious shock) is a serious complication of purulent-inflammatory diseases that occurs when a large number of bacteria and their toxins enter the bloodstream.

[1], [2], [3], [4], [5], [6], [7], [8]

Epidemiology

Septic shock occurs in the presence of purulent foci on the background of a decrease in reactivity and weakening of the body's immune system, as well as changes in the sensitivity of microflora to antibacterial drugs. Most often it develops after pneumonia or peritonitis, but it can also occur in other conditions: septic labor, septic abortion, infections of the bile ducts, thrombophlebitis, mesotympanitis, etc. Only in 5% of cases septic shock complicates urologic diseases: acute purulent pyelonephritis, abscess and carbuncle kidney, acute prostatitis, epididymoorkhit and purulent urethritis. In addition, it can occur against the background of an infectious-inflammatory process after instrumental research and surgical interventions.

Most researchers note an annual increase in the number of patients with sepsis by 8-10%, which emphasizes the urgency of the problem. After the introduction of recommendations for the diagnosis and treatment of sepsis and septic shock, developed by the International Expert Council, there was a decrease in the mortality rates of patients in 1995-2000.

High predisposition to the development of septic shock and its most severe course is observed in elderly and senile patients, weakened by a prolonged urological disease and infectious process. In addition, in this category of patients, often associated concomitant diseases (diabetes mellitus, chronic hepatitis, pancreatitis, anemia), which act as provoking and aggravating factors. A higher risk of sepsis and septic shock is experienced by patients with immunosuppression due to acquired immunodeficiency syndrome or organ transplantation, as well as after glucocorticoids and chemotherapy.

With the development of septic shock, close cooperation between urologists and resuscitators is necessary, as patients are in serious condition and need to monitor and quickly correct violations of vital organs with the use of complex and urgent resuscitation. Despite the improvement of diagnostic methods and introduction of new highly effective antibacterial drugs into practice, the lethality with septic shock remains high and reaches 60-90%.

[9], [10], [11], [12], [13], [14], [15], [16],

Causes of the septic shock in urological diseases

At the heart of the pathophysiological mechanism of the development of septic shock, along with the presence of infection is a specific sensitization of the body, resulting from a chronic inflammatory process in the organs of the urinary system, prolonged uremic and purulent intoxication. In this case, bacteria and their toxins act as antigens.

In most cases, sepsis and septic shock cause gram-negative microorganisms (Pseudomonas aeruginosa, Proteus, Escherichia coli, Klebsiella, Serratia, Enterobacteria, etc.), but it can also be caused by gram-positive bacteria (staphylococci, pneumococci, streptococci), fungi and, viruses and parasites. The state of humoral and cellular immunity depends on the entrance gate of the infection, the number of pathogens that get into the blood, their type, virulence and reactivity of the organism.

Factors predisposing patients with urological pathology to the development of sepsis include a violation of urinary outflow, anomalies in the development of the urinary tract and damage to their mucous membrane, the presence of concrements and reflux. Most often microorganisms penetrate into the bloodstream:

• through the forming kalikovenoznye shunts with increasing intrapulmonary pressure due to fornic reflux;
• through the mucous membrane of the bladder or urethra during instrumental research and catheterization;
• lymphogenous pathway at the break of the biological barrier of the lymph node as a result of a significant increase in the number of bacteria present in it.

Chronic urological diseases, in which antibacterial drugs are used for a long time, and changes in the body's immune status, contribute to the manifestation of pathogenicity of microorganisms and increase their resistance to bactericidal and bacteriostatic effects.

Despite a large number of works devoted to the study of the pathogenesis of septic shock, many of its links have not been studied thoroughly. At present, it has been established that peptides, cytokines released from monocytes, macrophages and endothelial cells, play a central role in regulating the expression and duration of the inflammatory response in the body with the stimulating effect of the infectious agent. They interact with cellular receptors and regulate the response of cells to inflammation. In sepsis, there is a disruption of the complex balance of pro- and anti-inflammatory reactions: the primary immunostimulating effect is followed by the immunosuppression phase in which IL-1, -6 and -8 are involved, tumor necrosis factor a, the excess release of which leads to the development of septic shock and death of patients. Thus, sepsis can be considered an inadequate response of the immune system that occurs when the regulation of inflammation activity changes.

The least studied mechanisms of development and clinical symptoms of organ failure in sepsis and septic shock.

Endotoxins have a histamine-and serotonin-like effect on the cardiovascular system, leading to a sharp increase in the capacity of the vascular bed and peripheral blood deposition. This reduces the venous return of blood to the heart, reduces cardiac output, blood pressure, worsens coronary blood flow. Under the influence of toxins, the contractile function of the myocardium decreases, followed by the development of microhemorrhages and microinfarctions. Azotemic intoxication, which occurs with concomitant chronic renal failure. It aggravates these pathological changes.

In septic shock, as a result of a spasm of the pulmonary capillary bed and a sharp increase in pulmonary-vascular resistance, a gas exchange violation occurs, to which disseminated intravascular hemocoagulation joins. All these factors lead to the formation of microthrombi in the pulmonary capillaries. In this case, blood from the opening arteriovenous shunts passes through the peripheral capillaries of organs and tissues and does not participate in gas exchange, which leads to the development of tissue hypoxia and aggravation of respiratory metabolic acidosis, in which the increased rate of breathing only temporarily compensates for the violation of gas exchange.

Progressive decrease in blood pressure, accompanied by a violation of microcirculation, leads to a deterioration of cerebral blood flow and the development of encephalopathy, the clinical signs of which, with the growth of renal insufficiency, are aggravated by uremic intoxication and acidosis.

Septic shock causes significant disturbances in the hemocoagulation system contributing to the occurrence of multi-organ failure. Against the backdrop of an operating injury, blood loss. Hemotransfusions, changes in rheological properties of blood (increase in viscosity), slowing of blood flow in the microcirculatory bed, the specific action of endo- and exotoxins leads to the destruction of red blood cells and platelets. At the same time, biologically active substances enter the bloodstream: thromboplastin, histamine, kinins, which cause a sharp activation of the coagulating system of blood, adhesion and aggregation of platelets. Damage of the vascular endothelium with toxins and immune complexes promotes the formation of aggregates of platelets with fibrin and the development of disseminated intravascular coagulation (ICD) of the blood. Due to the involvement of a large amount of fibrin in the process, there is coagulopathy of consumption (the phase of thrombohemorrhagic syndrome). Blockade of capillary blood flow by platelet-fibrin aggregates (thrombus), as well as multiple hemorrhages lead to tissue hypoxia and multiple organ failure.

Disturbances of hemodynamics, hypoxia of tissues and blockade of the microcirculatory bed by aggregates of uniform elements cause hemorrhages in the renal parenchyma, intravascular coagulation of blood and cortical necrosis, which leads to oliguria, which turns into anuria.

Under the action of endotoxins there is a spasm of the vessels of the portal system, which promotes the development of hepatonecrosis. At the same time, all the liver functions deteriorate and, to a greater extent, detoxification.

Septic shock is accompanied by the destruction and reduction of the content of formed elements (erythrocytes, leukocytes, platelets) in the blood. Leukopenia is usually short-lived and rapidly replaced by an increasing leukocytosis with a stab-shift leftward. Against the backdrop of worsening kidney and liver function in the blood, the level of urea, creatinine, bilirubin increases, and a gas exchange violation caused by increased uremic and purulent intoxication leads to the development of acidosis.

Pathological changes in microcirculation and ICE contribute to the violation of adrenal function (decrease in the level of catecholamines in the blood). Tissue hypoxia and activation of proteolytic enzymes cause the development of destructive processes in the pancreas (up to pancreatonecrosis).

[17], [18], [19], [20]

Symptoms of the septic shock in urological diseases

Septic shock in urological patients develops suddenly and is characterized by extremely severe course. The fulminant form occurs within 3-6 hours after the onset of the underlying disease, instrumental examination or surgical treatment. At late (delayed) form it develops on 2-5th day of the postoperative period, represented uncomplicated. Symptoms of septic shock depend on many factors: the general condition of the patient, his age and concomitant disease. Reactivity of the organism, parameters of cardiac activity, excretory function of the kidneys, etc.

In describing septic shock, specialists use a number of terms, with respect to the interpretation of which an international consensus has been reached. So. It was decided that the occurrence of the syndrome of a systemic inflammatory response is determined by the presence of at least two of the following symptoms:

• body temperature above 38 ° C or below 36 ° C;
• heart rate more than 90 per minute
• the respiratory rate is more than 20 per minute or PaCO2 is less than 32 mmHg. (4.3 kPa);
• the number of leukocytes in peripheral blood more than 12х109 / l or less 4х10 ⁹ / l;
• the content of immature (rod-shaped) forms is more or equal to 10%.

This syndrome is a response to a variety of factors affecting the infectious and non-infectious (eg, burns, pancreatitis) nature. The concept of infection implies the presence of microflora in those parts of the body. Which under normal conditions are sterile. In this case, an inflammatory reaction usually occurs. Sepsis is considered an activation of the syndrome of a systemic inflammatory response under the influence of a foci of infection in the body, the presence of which is confirmed by a bacteriological study. However, this diagnosis can be established regardless of the results of the latter. It is also accepted to isolate severe sepsis, which is accompanied by:

• violation of the functions of organs;
• insufficient perfusion of blood, which is indicated by lactic acidosis, oliguria or the development of an acute mental disorder;
• a decrease in systolic blood pressure below 90 mm Hg. Or more than 40 mm Hg. From the initial level (in the absence of other reasons).

Bacteremia - the presence of viable microorganisms in the blood serum. If during the examination with bacteremia it is not possible to detect the localization of the infectious process, then it is considered primary. In addition, transient bacteremia, usually observed with damage to the mucous membranes, as well as secondary bacteremia (the most common) due to the presence of an infectious focus outside or inside the vascular bed is isolated. Thus, the underlying symptom of septic shock is a reduction in arterial pressure due to sepsis, which can not be corrected by infusion therapy, in conjunction with pathological symptoms caused by insufficient blood perfusion. Septic shock, which can not be corrected during the first hour of infusion and drug therapy, is called refractory.

There are three stages of septic shock: early (prodromal), clinically pronounced and irreversible.

The main signs of the early stage: high body temperature, chills, hyperemia and dry skin, oliguria, vomiting, diarrhea. When examined, patients can behave inadequately, excited, euphoric. Hemodynamic parameters are stable; possible tachycardia, increased frequency of respiration. In the blood - a slight respiratory alkalosis, gradually develops hypoxemia of peripheral tissues. This stage of shock is usually short-lived and not always correctly recognized. It is often denoted by clinical terms "attack pyelonephritis" or "urethral fever." The forecast is favorable. With prolonged flow, there are significant violations of hemodynamics: increased tachycardia, lower blood pressure and central venous pressure (CVP); the respiratory alkalosis is replaced by metabolic acidosis, which worsens the prognosis.

Clinically pronounced stage of septic shock ("shock in progress") in urological practice is recognized most often. The patients reluctantly come into contact, are inhibited, sleepy. On examination, note the pallor and importance of the skin, icteric sclera; possible cyanosis and enlargement of the liver. The hectic body temperature is replaced by subfebrile. Observe vomiting and diarrhea: oliguria turns into anuria. Tachycardia reaches 120-130 per minute, cardiac output, blood pressure, CVP and BCC decrease. With ECG, signs of deterioration of the coronary circulation are determined. Progression of uremic intoxication is accompanied by severe hypoxemia and metabolic acidosis. The prognosis is largely determined by the timeliness of complex intensive therapy aimed at normalizing hemodynamic parameters and reducing hypercoagulation. In urological practice, also observed erased forms of septic shock that occurs against a background of prolonged purulent-septic and azotemic intoxication, intermittent or terminal stage of chronic renal failure.

The irreversible stage of septic shock in urological patients usually develops against the background of the terminal stage of chronic renal failure. Patients are observed confused consciousness, pallor, hysteria of the skin, hemorrhages on it. Chills. In this case, the signs of hypovolemic shock (a decrease in the artheal pressure to 60 mm Hg and below the negative CVP indices) are poorly amenable to correction, against the background of frequent and superficial breathing there is pronounced hypoxemia and decompensated acidosis, cardiac, renal and hepatic insufficiency progresses. Disturbed hemocoagulation. Irreversible changes in internal organs can lead to death in the first hours after the onset of the development of this stage of shock.

Diagnostics of the septic shock in urological diseases

The mandatory components of the diagnosis of septic shock include a clinical blood test with the calculation of the leukocyte formula. This condition is characterized by leukocytosis (up to 20-30x10 ⁹ / l and more), pronounced shift of the leukocyte formula to the left, an increase in ESR. With cytolysis of the blood elements, hemolysis is determined. Bacteriological examination of blood and determination of the sensitivity of the isolated microflora to antibacterial drugs is recommended to be carried out before the beginning of treatment and repeated 2-3 times with an interval of 12-24 hours.

With oliguria and anuria, an increase in the level of creatinine, urea, and potassium in the blood is noted; with dysfunction of the liver and pancreas, an increase in the concentration of bilirubin, an increase in the activity of transaminases, lactate dehydrogenase, amylase, alkaline phosphatase.

When studying the state of the immune system, various changes are determined: a decrease in the number of T-lymphocytes, a decrease in the concentration of immunoglobulins and proteins of the complement system, and in later periods an increase in the content of specific antibodies.

Against the backdrop of toxemia and the destruction of blood cells under septic shock, release of cellular thromboplastin and other biologically active substances serving as triggers for the development of DIC syndrome occurs. The main symptoms of which are thromboses and hemorrhages. In the initial stage of septic shock, a decrease in the time of blood coagulation is noted, and changes in thromboelastogram are characteristic of those with hypercoagulable shear. The formation of numerous blood clots in the microcirculatory bed leads to coagulopathy of consumption: there is thrombocytopenia, hyperfibrinogenemia, the content of antithrombin III decreases, and fibrinogen degradation products appear in the blood.

Later, a hypocoagulant shift occurs with an increase in serum fibrinolytic activity, recalcification time, thrombin time and total clotting time. The transition of the DIC syndrome to the third stage (fibrinolysis) can be explained by the manifestation of anticoagulant properties of toxins and decomposition products of blood elements on the background of depletion of plasma clotting factors. This condition threatens the life of the patient due to the risk of fibrinolytic bleeding. At which the blood loses its ability to coagulate.

In this case, an extremely low level of fibrinogen, an increase in thrombin time, a gradual decrease in the number of platelets, a decrease in the content of antithrombin III. Paracoagulation tests are negative, trombotest reaches I-II degree. Thus, the progressive development of DIC syndrome with microcirculatory blockade and hypoxic injuries of internal organs makes a significant contribution to the development of irreversible changes and low effectiveness of resuscitation in septic shock.

[21], [22], [23], [24], [25]

Treatment of the septic shock in urological diseases

Therapeutic measures for septic shock include general resuscitation measures aimed at restoring the functions of vital organs, and specific treatment methods associated with urological disease.

General resuscitation measures. The most important factor in saving a patient's life is the time of the beginning of treatment. In accordance with the international guidelines for the management of patients with severe sepsis and septic shock in 2008, with a reduction in blood pressure or an increase in serum lactate levels above 4 mmol / l, the patient should immediately be transferred to the intensive care unit, in which conditions it is necessary to perform therapeutic measures aimed at maintaining CVP within 8-12 mm of water. Systolic blood pressure above 65 mm Hg, urine output exceeding 0.5 ml / kgh), oxygen saturation in the upper sex th vein more than 70%. If it is not possible to achieve the required values of the latter, it is recommended to continue the infusion therapy, transfusion of erythrocyte mass to reach a hematocrit level of 30%. Administration of dobutamine at a rate of no more than 20 μg / (kg-min) and in the absence of effect - transfer of the patient to mechanical ventilation. When ventilation is necessary to maintain higher CVP (within 12-15 mm Hg).

Treatment activities usually begin with the catheterization of the main veins (humerus, subclavian, jugular) and the installation of one or two transfusion systems with preparations of hydroxyethyl starch or dextran and solutions of crystalloids (Ringer's solution, isotonic sodium chloride, sodium acetate + sodium chloride, sodium hydrogen carbonate + sodium chloride + potassium chloride, etc.). This combination is aimed at eliminating hypovolemia, improving microcirculation, normalizing the rheological properties of blood (hemodilution and reducing viscosity), reducing the concentration of toxins in the blood. Transfusion is performed under the control of CVP, ECG and diuresis; the volume of it should be at least 3-5 liters per day (in severe cases - up to 1 l / h). To eliminate acidosis, sodium bicarbonate and other buffer solutions are used.

When carrying out transfusion therapy, the most important role is played by protein preparations (5-20% albumin, protein, dry, uncitrated, native concentrated and fresh frozen plasma, factor of blood coagulation VIII), which contribute to active replenishment of bcc and protein deficiency in the body, and also neutralize toxins and the supply of procoagulants necessary for the management of DIC syndrome.

With the growth of hemodynamic disorders, the use of vasoconstrictors is necessary. Intravenous dosing through the transfusion system of a 0.2% solution of norepinephrine or a 0.5% solution of dopamine is indicated with a reduction in arterial pressure to 90 mm Hg. Dopamine allows you to increase coronary and renal blood flow disproportionately to the increase in cardiac output, which is especially important when there are signs of acute kidney failure. Under the conditions of toxemia, a 20% dextrose solution with soluble insulin (1 unit of insulin per 4 g of glucose) is administered to maintain the energy reserves of the myocardium. Cardiotropic therapy can be supplemented by the introduction of inosine, phosphocreatine, B vitamins, and others.

With the preservation of hypotension against a background of full-fledged infusion therapy and the use of vasopressors, the administration of glucocorticoids is indicated. Hydrocortisone is added to the transfusion solution, the dose of which should not exceed 300 mg per day. Stabilization of hemodynamic parameters with a minimum infusion rate is achieved in the absence of signs of deterioration of the coronary circulation on the ECG, preservation of arterial pressure indices peculiar to a specific patient (not less than 100-110 mm Hg). And the level of CVP is not lower than 40-60 mm of water.

Transfusion of erythrocyte mass is recommended with a decrease in hemoglobin below 70 g / l. It should be maintained within 70-90 g / l, and if necessary (signs of myocardial ischemia, severe hypoxia, hemorrhagia acidosis) - and higher. It is necessary to control the content of platelets in the blood and compensate for their deficiency with a decrease less than 50x109 / l; for patients with a high risk of hemorrhage, their content should be 50-300 x 109 / l. Higher values of this indicator should be provided before surgery and invasive procedures.

Against the background of septic shock in urological patients, as a rule, acute respiratory distress and hypoxemia develop, the cause of which is the blockade of the pulmonary-capillary bed associated with the DIC syndrome. In this case, there are indications for intubation of the trachea and ventilation. To ensure a full-fledged ventilation, pH, PaCO2, and PaO2 should be taken into account, since under the conditions of blockade of the microcirculatory bed and arteriovenous blood shunting, the state of gas exchange can be judged only by the parameters of the gas composition of the blood and the acid-base balance. If it is not possible to perform blood gas analysis, the ventilation is performed in the hyperventilation mode (about 130% to the proper value of the minute volume of breathing).

In the treatment of patients with septic shock, dynamic monitoring of biochemical parameters is carried out and, if necessary, appropriate correction is carried out. So. The administration of appropriate doses of insulin may be required with an increase in glucose levels above 8 mmol / l. With increasing renal failure, hemodialysis is performed. In addition, for the prevention of deep vein thrombosis (in the absence of contraindications), low doses of low-molecular sodium heparin are prescribed, and histamine H2-blockers or proton pump inhibitors are used to prevent the formation of stress ulcers.

After stabilization of hemodynamics with a normal outflow of urine, it is possible to stimulate diuresis with osmo- and saluretic drugs. In elderly and senile patients, furosemide in large doses should be used with caution, since the excretion of a large amount of potassium can adversely affect the contractile function of the myocardium, as well as the removal of large volumes of fluid can aggravate the initial hyperkalemia. When using the method of forced diuresis, it is necessary to control the electrolyte composition of the blood and conduct an electrocardiogram. With the development of hypokalemia, correction of solutions of potassium and magnesium asparaginate (panangin, asparcam), glucose-insulin-potassium mixture is carried out.

Specific treatment for septic shock. A specific component of complex treatment of patients with septic shock is antibiotic therapy with the use of drugs that affect the etiologic link of the infectious inflammatory process. The most frequent pathogens of urological infections are representatives of the opportunistic microflora; In addition, the role of antibiotic-resistant bacteria increases in the genesis of purulent-septic complications. Given these facts, it is recommended to carry out a bacteriological study of all possible sources of bacteremia and determine the sensitivity of microorganisms to antibacterial drugs, and in the development of septic shock - the appointment of empirical antimicrobial therapy, taking into account the type of prospective pathogen and the ways of its entry into the body. - An essential condition for successful treatment is the elimination of obstruction of the urinary ways and normalization of the passage of urine.

With sepsis and septic shock, intravenous antibacterial drugs should be started as soon as possible - within the first hour after diagnosis.

The most common pathogens of sepsis and septic shock in "logical diseases are the E. Coli and other enterobacteria. In patients infected with nosocomial strains, they detect antibiotic-resistant Pseudomonas aeruginosa, Proteus, Klebsiella-Enterobacter serratsia. Drugs of choice effective against these groups of microorganisms:

• cephalosporins of the third generation (cefotaxime, ceftriaxone, ceftizoxime, cefodizim, ceftazidime, cefoperazone);
• fluoroquinolones (ciprofloxacin, ofloxacin, lomefloxacin against gram-negative microorganisms, levofloxacin, gatifloxacin against gram-positive microflora);
• carbapenems (imipenem, meropenem);
• aminoglycosides (amikacin, tobramycin, gentamicin);
• "Protected" semisynthetic penicillins (ampicillin + sulbactam or piperacillin + tazobactam).

After receiving the results of the bacteriological study, antimicrobial therapy continues, taking into account the results of determining the sensitivity of microorganisms, the least toxic preparation. When detecting the bacteria of the Pseudomonas aeruginosa group, the combined treatment is most effective.

Recommended doses of antibiotics should be close to or equal to the maximum daily dose. Treatment should continue until the patient's condition is stabilized and within 3-4 days after the normalization of body temperature. The total duration of the course of antibiotic chemotherapy is usually 7-10 days, but with a slow development of positive dynamics, the inability to drain the focus of infection or with the concomitant immunodeficiency state, the duration of treatment should be increased.

The peculiarity of antibacterial chemotherapy in urological patients is the need for dose adjustment depending on the degree of impairment of the excretory function of the kidneys. With the development of septic shock against the background of chronic renal failure in the first day of treatment after the restoration of passage urine prescribed maximum doses of antibiotics. Further, taking into account the primary excretion of drugs from the body by the kidneys and the nephrotoxicity of individual drugs, the treatment is carried out taking into account the parameters of renal filtration, diuresis, the concentration ability of the kidneys, the blood content of total nitrogen, urea, creatinine.

In the complex treatment of patients in whom septic shock is observed, efferent treatment methods are used: indirect electrochemical oxidation of blood with sodium hypochlorite solution; ultraviolet irradiation of blood (5-10 sessions for 20 minutes), as well as sorption methods of detoxification - hemosorption and plasmosorption.

The fight against nosocomial infections, carefully selected antibiotic therapy with directed drugs, shortening of hospital stay, the early removal of permanent urethral catheters, the use of closed drainage systems for urinary tract and drainage, and compliance with aseptic rules play an important role in the prevention of purulent-septic complications of urological diseases.