Septic shock in urologic diseases

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

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Epidemiology

Septic shock occurs in the presence of purulent foci against the background of decreased reactivity and weakening of the body's immune system, as well as with a change in the sensitivity of microflora to antibacterial drugs. Most often, it develops after pneumonia or peritonitis, but can also occur in other conditions: septic childbirth, septic abortion, biliary tract infections, thrombophlebitis, mesotympanitis, etc. Only in 5% of cases does septic shock complicate urological diseases: acute purulent pyelonephritis, abscess and carbuncle of the kidney, acute prostatitis, epididymoorchitis and purulent urethritis. In addition, it can occur against the background of an infectious and inflammatory process after instrumental studies and surgical interventions.

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

A high predisposition to the development of septic shock and its most severe course are observed in elderly and senile patients weakened by a long-term urological disease and an infectious process. In addition, this category of patients often has concomitant diseases (diabetes mellitus, chronic hepatitis, pancreatitis, anemia), which act as provoking and aggravating factors. A higher risk of sepsis and septic shock development is found in patients with immunosuppression caused by acquired immunodeficiency syndrome or organ transplantation, as well as after chemotherapy and glucocorticoid treatment.

In the development of septic shock, close cooperation between urologists and resuscitators is necessary, since patients are in serious condition and require monitoring and rapid correction of dysfunctions of vital organs using complex and emergency resuscitation measures. Despite the improvement of diagnostic methods and the introduction of new highly effective antibacterial drugs into practice, the mortality rate in septic shock remains high and reaches 60-90%.

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Causes of septic shock in urologic diseases.

The pathophysiological mechanism of septic shock development, along with the presence of infection, is based on specific sensitization of the body, which occurs as a result of 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 are caused by gram-negative microorganisms (Pseudomonas aeruginosa, Proteus, Escherichia coli, Klebsiella, Serratia, Enterobacter, etc.), but it can also be caused by gram-positive bacteria (staphylococci, pneumococci, streptococci), fungi, and possibly viruses and parasites. The state of humoral and cellular immunity depends on the entry point of infection, the number of pathogens that have entered the blood, their type, virulence, and the reactivity of the body.

Factors predisposing patients with urological pathology to the development of sepsis include impaired urine outflow, abnormalities in the development of the urinary tract and damage to its mucous membrane, the presence of stones and reflux. Most often, microorganisms enter the bloodstream:

• through the forming calicovenous shunts with an increase in intra-pelvic pressure due to fornical reflux;
• through the mucous membrane of the bladder or urethra during instrumental examinations and catheterization;
• lymphogenous route when the biological barrier of the lymph node is broken through as a result of a significant increase in the number of bacteria in it.

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

Despite the large number of works devoted to the study of the pathogenesis of septic shock, many of its links have not been fully studied. At present, it has been established that the central role in the regulation of the severity and duration of the inflammatory response in the body is played by peptides - cytokines released from monocytes, macrophages and endothelial cells under the stimulating effect of an infectious agent. They interact with cellular receptors and regulate the cellular response to inflammation. In sepsis, a violation of the complex balance of pro- and anti-inflammatory reactions occurs: the primary immunostimulating effect is followed by a phase of immunodepression, which involves IL-1, -6 and -8, tumor necrosis factor a, the excessive 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, arising against the background of a change in the regulation of inflammatory activity.

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

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. At the same time, venous return of blood to the heart decreases, cardiac output and arterial pressure decrease, and coronary blood flow worsens. Under the influence of toxins, the contractile function of the myocardium decreases with the subsequent development of microhemorrhages and microinfarctions. Azotemic intoxication, which occurs with concomitant chronic renal failure, aggravates these pathological changes.

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

A progressive decrease in blood pressure, accompanied by a disruption of microcirculation, leads to a deterioration in cerebral blood flow and the development of encephalopathy, the clinical signs of which, with increasing renal failure, are aggravated by uremic intoxication and acidosis.

Septic shock causes significant disturbances in the hemocoagulation system, which contribute to the development of multiple organ failure. Against the background of surgical trauma, blood loss, hemotransfusions, changes in the rheological properties of the blood (increased viscosity), slowing of blood flow in the microcirculatory bed, the specific action of endo- and exotoxins leads to the destruction of erythrocytes and platelets. At the same time, biologically active substances enter the blood: thromboplastin, histamine, kinins, which cause a sharp activation of the blood coagulation system, adhesion and aggregation of platelets. Damage to the vascular endothelium by toxins and immune complexes contributes to the formation of platelet aggregates with fibrin and the development of disseminated intravascular coagulation (DIC) of the blood. Due to the involvement of a large amount of fibrin in the process, consumption coagulopathy occurs (the phase of thrombohemorrhagic syndrome). Blockage of capillary blood circulation by platelet-fibrin aggregates (thrombi), as well as multiple hemorrhages lead to tissue hypoxia and multiple organ failure.

Hemodynamic disturbances, tissue hypoxia and blockade of the microcirculatory bed by aggregates of formed elements cause hemorrhages in the renal parenchyma, intravascular blood coagulation and cortical necrosis, which leads to oliguria, turning into anuria.

Under the influence of endotoxins, spasm of the portal system vessels occurs, which contributes to the development of hepatonecrosis. At the same time, all liver functions are sharply impaired, and to a greater extent - detoxification.

Septic shock is accompanied by the destruction and decrease in the content of formed elements (erythrocytes, leukocytes, thrombocytes) in the blood. Leukopenia is usually short-term and quickly gives way to increasing leukocytosis with a shift to the left for band cells. Against the background of deteriorating kidney and liver function, the level of urea, creatinine, and bilirubin in the blood increases, and the disruption of gas exchange caused by increased uremic and purulent intoxication leads to the development of acidosis.

Pathological changes in microcirculation and DIC contribute to dysfunction of the adrenal glands (reduction 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 pancreatic necrosis).

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Symptoms of septic shock in urologic diseases.

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

When describing septic shock, specialists use a number of terms, with an international consensus on their interpretation. Thus, it was decided that the occurrence of systemic inflammatory response syndrome is determined by the presence of at least two of the following signs:

• body temperature above 38 C or below 36 C;
• heart rate over 90 beats per minute
• respiratory rate greater than 20 per minute or PaCO2 less than 32 mmHg (4.3 kPa);
• the number of leukocytes in the peripheral blood is more than 12x109/l or less than 4x109 ^/ l;
• the content of immature (band) forms is more than or equal to 10%.

This syndrome is a response to various factors of infectious and non-infectious (e.g. burns, pancreatitis) nature. The concept of infection implies the presence of microflora in those areas of the body that are sterile under normal conditions. In this case, an inflammatory reaction usually occurs. Sepsis is considered to be the activation of the systemic inflammatory response syndrome under the influence of an infectious focus in the body, the presence of which is confirmed by bacteriological testing. However, this diagnosis can be established regardless of the results of the latter. It is also customary to distinguish severe sepsis, which is accompanied by:

• dysfunction of organs;
• insufficient blood perfusion, as evidenced by lactic acidosis, oliguria, or the development of acute mental disorder;
• a decrease in systolic blood pressure below 90 mmHg or more than 40 mmHg from the initial level (in the absence of other causes).

Bacteremia is the presence of viable microorganisms in the blood serum. If the examination of bacteremia fails to detect the localization of the infectious process, it is considered primary. In addition, there is transient bacteremia, usually observed with damage to the mucous membranes, as well as secondary bacteremia (the most common), caused by the presence of an infectious focus outside or inside the vascular bed. Thus, the fundamental sign of septic shock is a decrease in blood pressure due to sepsis, which cannot be corrected by infusion therapy, in combination with pathological symptoms caused by insufficient blood perfusion. Septic shock, which cannot be corrected within the first hour of infusion and drug therapy, is called refractory.

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

The main signs of the early stage are: high body temperature, chills, hyperemia and dry skin, oliguria, vomiting, diarrhea. On examination, patients may behave inappropriately, be excited, euphoric. Hemodynamic parameters are stable; tachycardia and increased respiratory rate are possible. In the blood - slight respiratory alkalosis, hypoxemia of peripheral tissues gradually develops. This stage of shock is usually short-lived and is not always correctly recognized. It is often designated by the clinical terms "pyelonephritis attack" or "urethral fever". The prognosis is favorable. With a protracted course, significant hemodynamic disturbances are noted: increased tachycardia, decreased arterial pressure and central venous pressure (CVP); respiratory alkalosis is replaced by metabolic acidosis, which worsens the prognosis.

The clinically expressed stage of septic shock ("shock in progress") is recognized most often in urological practice. Patients are reluctant to make contact, are inhibited, drowsy. During examination, pale and important skin, icteric sclera are noted; cyanosis and liver enlargement are possible. Hectic body temperature is replaced by subfebrile. Vomiting and diarrhea are observed: oliguria turns into anuria. Tachycardia reaches 120-130 per minute, cardiac output, arterial pressure, CVP and BCC decrease. ECG reveals signs of deterioration of coronary circulation. 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, a latent form of septic shock is also observed, arising against the 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 have confusion, paleness, hysteria of the skin, hemorrhages on it. Chills. At the same time, the signs of hypovolemic shock (a decrease in arterial pressure to 60 mm Hg and below, negative CVP indicators) are difficult to correct, against the background of frequent and shallow breathing, severe hypoxemia and decompensated acidosis occur, cardiac, renal and hepatic failure progresses. Hemocoagulation is impaired. Irreversible changes in internal organs can lead to death during the first hours from the onset of this stage of shock.

Diagnostics of septic shock in urologic diseases.

Mandatory components of septic shock diagnostics include a clinical blood test with a white blood cell count. This condition is characterized by leukocytosis (up to 20-30x10 ⁹ /l or more), a pronounced shift in the white blood cell count to the left, and an increase in ESR. Hemolysis is determined with cytolysis of blood cells. Bacteriological blood testing and determination of the sensitivity of the isolated microflora to antibacterial drugs are recommended before treatment and repeated 2-3 times at intervals of 12-24 hours.

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

When examining 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 complement system proteins, and, at a later stage, an increase in the content of specific antibodies.

Against the background of toxemia and destruction of blood cells in septic shock, cellular thromboplastin and other biologically active substances are released, which serve as triggers for the development of DIC syndrome. The main symptoms of which are thrombosis and hemorrhage. In the initial stage of septic shock, a decrease in blood clotting time is noted, and changes in the thromboelastogram are characteristic of those with a hypercoagulation shift. The formation of numerous thrombi in the microcirculatory bed leads to consumption coagulopathy: thrombocytopenia and hyperfibrinogenemia occur, the content of antithrombin III decreases, and fibrinogen degradation products appear in the blood.

Subsequently, a hypocoagulation shift occurs with an increase in the fibrinolytic activity of the serum, recalcification time, thrombin time and total blood clotting time. The transition of DIC syndrome to the third stage (fibrinolysis) can be explained by the manifestation of the anticoagulant properties of toxins and decay products of blood cells against the background of depletion of plasma coagulation factors. This condition threatens the patient's life due to the risk of developing fibrinolytic bleeding, in which the blood loses its ability to clot.

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

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Treatment of septic shock in urologic diseases.

Treatment of septic shock includes general resuscitation measures aimed at restoring the functions of vital organs and specific treatment methods associated with the urological disease.

General resuscitation measures. The most important factor in saving the patient's life is the time of treatment initiation. In accordance with the international recommendations for the management of patients with severe sepsis and septic shock adopted in 2008, if blood pressure drops or the lactate level in the blood serum increases above 4 mmol/l, the patient should be immediately transferred to the intensive care unit, where it is necessary to carry out therapeutic measures aimed at maintaining central venous pressure within 8-12 mm H2O, systolic blood pressure above 65 mm Hg, urine output above 0.5 ml/kg h), and blood oxygen saturation in the superior vena cava above 70%. If the required values of the latter cannot be achieved, then continuation of infusion therapy and transfusion of red blood cells until the hematocrit level reaches 30% are recommended. administration of dobutamine at a rate of no more than 20 mcg/(kg x min) and, if there is no effect, transfer the patient to mechanical ventilation. During mechanical ventilation, it is necessary to maintain higher CVP values (within 12-15 mm Hg).

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

During transfusion therapy, protein preparations (5-20% albumin, protein, dry citrate-free, native concentrated and fresh frozen plasma, blood coagulation factor VIII) play a key role, as they promote active replenishment of the BCC and protein deficiency in the body, and also ensure the neutralization of toxins and the supply of procoagulants necessary to stop DIC syndrome.

With increasing hemodynamic disorders, it is necessary to use vasoconstrictors. Intravenous dosed administration of 0.2% norepinephrine or 0.5% dopamine via a transfusion system is indicated when arterial pressure decreases to 90 mm Hg. Dopamine increases coronary and renal blood flow disproportionately to the increase in cardiac output, which is especially important when signs of acute renal failure occur. In conditions of toxemia, a 20% dextrose solution with soluble insulin (1 U of insulin per 4 g of glucose) is administered to maintain myocardial energy reserves. Cardiotropic therapy can be supplemented with the administration of inosine, phosphocreatine, B vitamins, etc.

If hypotension persists despite adequate infusion therapy and the use of vasopressors, glucocorticoids are indicated. Hydrocortisone is added to the transfusion solution, the dose of which should not exceed 300 mg per day. Stabilization of hemodynamic parameters at a minimum infusion rate is achieved in the absence of signs of deterioration of coronary circulation on the ECG, maintaining arterial pressure parameters characteristic of a specific patient (not lower than 100-110 mm Hg) and the level of central venous pressure not lower than 40-60 mm H2O.

Transfusion of red blood cells is recommended when the hemoglobin level drops below 70 g/l. It should be maintained within 70-90 g/l, and if necessary (signs of myocardial ischemia, severe hypoxia, hemorrhages, acidosis) - and higher. It is necessary to monitor the platelet content in the blood and compensate for their deficiency when it drops below 50x109/l; for patients with a high risk of blood loss, their content should be 50-300x109/l. Higher values of this indicator should be ensured before surgical interventions and invasive procedures.

Against the background of septic shock in urological patients, as a rule, acute respiratory disorders and hypoxemia develop, the cause of which is the blockade of the pulmonary-capillary bed associated with DIC syndrome. In this case, there are indications for tracheal intubation and artificial ventilation. To ensure a full-fledged ventilation mode, pH, PaCO2, and PaO2 should be taken into account, since under conditions of blockade of the microcirculatory bed and arteriovenous shunting of blood, the state of gas exchange can only be judged by the parameters of the gas composition of the blood and acid-base balance. If it is impossible to perform blood gas analysis, artificial ventilation is carried out in the hyperventilation mode (about 130% of the required value of the minute respiratory volume).

When treating patients with septic shock, dynamic monitoring of biochemical parameters is performed and, if necessary, appropriate correction is made. Thus, the introduction of appropriate doses of insulin may be required when the glucose level rises above 8 mmol/l. When renal failure increases, hemodialysis is performed. In addition, low doses of low-molecular sodium heparin are prescribed to prevent deep vein thrombosis (in the absence of contraindications), and H2-histamine receptor blockers or proton pump inhibitors are prescribed to prevent the formation of stress ulcers.

After hemodynamic stabilization with normal urine outflow, diuresis can be stimulated with osmo- and saluretics. 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, just as the excretion of large volumes of fluid can aggravate the initial hyperkalemia. When using the forced diuresis method, it is necessary to monitor the electrolyte composition of the blood and perform an ECG. If hypokalemia develops, correction is carried out with solutions of potassium and magnesium aspartate (panangin, asparkam), a glucose-insulin-potassium mixture.

Specific treatment for septic shock. A specific component of the complex treatment of patients with septic shock is antibacterial therapy using drugs that affect the etiologic link of the infectious inflammatory process. The most common pathogens of urological infections are representatives of 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 conduct a bacteriological study of all possible sources of bacteremia and determine the sensitivity of microorganisms to antibacterial drugs, and in the event of septic shock, to prescribe empirical antimicrobial therapy taking into account the type of the suspected pathogen and the routes of its penetration into the body. A necessary condition for successful treatment is the elimination of obstruction of the urinary tract and normalization of urine passage.

In case of sepsis and septic shock, it is necessary to begin intravenous administration of antibacterial drugs as soon as possible - within the first hour after diagnosis.

The most common pathogens causing sepsis and septic shock in „logical diseases are Escherichia coli and other enterobacteria. In patients infected with hospital strains, antibiotic-resistant Pseudomonas aeruginosa, Proteus, and bacteria of the Klebsiella-Enterobacter-Serratia group are found. The drugs of choice that are effective against these groups of microorganisms are:

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

After receiving the results of the bacteriological examination, antimicrobial therapy is continued, taking into account the results of determining the sensitivity of microorganisms, with the least toxic drug. When bacteria of the Pseudomonas aeruginosa group are detected, combined treatment is most effective.

The recommended doses of antibiotics should be close to or correspond to the maximum daily doses. Treatment should be continued until the patient's condition stabilizes and for 3-4 days after the body temperature has returned to normal. The total duration of the course of antibacterial chemotherapy is usually 7-10 days, but with slow development of positive dynamics, inability to drain the source of infection, or with concomitant immunodeficiency, the duration of treatment should be increased.

The peculiarity of antibacterial chemotherapy in urological patients is the need to adjust the dose depending on the degree of impairment of the excretory function of the kidneys. In the development of septic shock against the background of chronic renal failure, maximum doses of antibiotics are prescribed on the first day of treatment after the restoration of urine passage. Subsequently, taking into account the predominant excretion of drugs from the body by the kidneys and the nephrotoxicity of individual drugs, treatment is carried out taking into account the indicators of renal filtration, diuresis, renal concentrating capacity, blood levels of total nitrogen, urea, and creatinine.

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

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