Principles of treatment of sepsis

Principles of treatment of sepsis. Sepsis (infection of the blood) is an acute or chronic disease characterized by a progressive spread of the bacterial, viral or fungal flora in the body. Sepsis may be the result of bacterial contamination of the body from a known source of inflammation (suppuration), but often the entrance gates of infection remain unclarified. Sepsis can be acute, sometimes almost instantaneously (when in the absence of proper treatment, death occurs within a few hours or days) or chronically. Currently, the nature of the course of sepsis varies significantly as a result of early antibiotic therapy.

Etiology. The causative agents of sepsis can be pathogenic, conditionally pathogenic microorganisms: cocci (staphylococci, pneumococci, meningococci), E. coli, Pseudomonas aeruginosa, Mycobacterium tuberculosis, Klebsiella, etc.; Viruses of the herpetiform group, etc.; Fungi of the type Candida, Aspergillus.

Pathogenesis. The generalization of the infection is due to the prevalence of the pathogen over the bacteriostatic capabilities of the organism as a result of massive invasion (for example, the breakthrough of the abscess into the blood from the infected thrombus, when trying to squeeze the furuncle, from the infected platelet mass, etc.) or congenital or acquired immunosuppression. Immunities that precede sepsis usually remain undetectable, except for cases of hematopoiesis depression. However, sepsis does not arise as a result of immunity disorders in general, but as a result of a breakdown in one of its links leading to a disruption in the production of antibodies, a decrease in phagocytic activity or activity of lymphocyte production, etc. Therefore, in most cases, sepsis is caused by one pathogen, Which is normally impeded by the immune response, that is, a certain part of it that turns out to be genetically or acquired damaged; The change of pathogens during one disease is an exception, not a rule. Simultaneous coexistence of several pathogens, their change is observed with immunosuppression caused by the use of cytostatics, depression of hematopoiesis as a result of aplasia of the bone marrow or its leukemic damage, the action of intense insolation and sunburn, roughly suppressing the immune response in several links. Recurrent septic bacterial infection is noted with hereditary defects of complement C2, properdin and other factors of the complement system. At gross defects of immunity often there are so-called opportunistic infections caused by conditionally pathogenic flora, saprophytes. Approximately about 10% of septic conditions are due to a combination of pathogens. Polymicrobial sepsis occurs in disorders of immunity associated with the absence of the spleen, disorders of the cellular (T-helper) link of immunity in AIDS.

In adults and children without obvious causes of immunodeficiency (cytostatic, steroid therapy, etc.) most often the causative agent of sepsis is staphylococcus or pneumococcus, less often meningococcus. Against the backdrop of cytostatic therapy (especially in conditions of nosocomial infection) an important role is played by gram-negative microflora (intestinal or pseudomonas aeruginosa, prothea). The causative agent of sepsis from an infected thrombus of the aortic aneurysm, the system of the inferior vena cava (more distant than the filter installed in it), the subclavian vein (with a long standing catheter in it) can be staphylococci, and Pseudomonas aeruginosa and pneumococcus. Lymphoprophylactic tumors and lymphophanulomatosis are accompanied by a violation of antiviral immunity, which leads to generalized herpetic infections (chicken pox, shingles, herpes simplex) until sepsis. With violations of neutrophilopoiesis as a result of hereditary neutropenia, recurrent staphylococcal infections occur sometimes with the development of staphylococcal sepsis. With long-term use of steroid hormones, chronic or acute bacterial septic processes and tuberculous sepsis are possible.

After removal of the spleen (for any reason) there is a predisposition to septic conditions more often meningo-coccus or pneumococcal etiology. The spleen is able to phagocytize neipsonized, non-antibody-bound bacteria, encapsulated bacteria (particularly pneumococci and meningococci), whereas in the liver only well-molded bacteria are phagocytosed. In order for the liver to take over the function of destroying encapsulated, nepsonized bacteria after removal of the spleen, it is necessary to introduce large volumes of fresh plasma containing opsonins. After splenectomy, the plasma content of such opsonins, such as properdin, tuftsin, produced predominantly by the spleen and necessary for phagocytosis of microorganisms by neutrophils, is reduced. Properdin is also a factor that triggers an additional way of activating the complement system (with component C3) - one of the important links of humoral immunity. Finally, the spleen produces mainly immunoglobulin M. The lack of all these factors contributes to the development of the deadly post-selenectomic syndrome.

An important role in the spread of infection is the formation of the syndrome of disseminated intravascular coagulation (DVS). Massive infection serves as the basis for tissue decay, the release of kinins and proteolytic enzymes into the blood, which contribute to impairment of vascular permeability, stasis, thrombosis in the microcirculation system. Multiple thromboses become the environment for the growth of microflora. In the development of DIC-syndrome in sepsis, an essential role is played by endotoxin-lipopolysaccharide from the wall of the E. coli, capsular polysaccharide pneumococcus, coagulase produced by the capsule of staphylococcus, and other products of the bacterial cell. One of the most studied ways of exciting the DIC syndrome in sepsis is the activation of the XII coagulation factor (Hageman factor). Influencing the vascular wall, endotoxin activates the XII factor, which leads to an increase in clotting, the formation of kallikrein and its precursors, and together with them the activation of fibrinolysis (transformation of the plasminogen into plasmin), the formation of kinins, activation of the complement system. Accumulation of bradykinin leads to the development of shock-dropping blood pressure, increased vascular permeability and microcirculation disorders.

DIC-syndrome and shock-permanent complications of sepsis caused by gram-negative microorganisms, meningococci, acute pneumococcal and staphylococcal sepsis. The accumulation of kinins in sepsis and DIC syndrome is facilitated by the depletion of enzymes such as kininase, an inhibitor of kallikrein, usually contained in the plasma of healthy individuals. The fibrinolysis, activated at the onset of DIC, is then sharply reduced due to the depletion of HA factor, kallikrein, and plasminogen itself. Oppression of fibrinolysis is a characteristic sign of DIC syndrome complicating sepsis. When microthrombi is infected, the DIC syndrome inevitably leads to a severe polyorganic pathology, in which the infection plays an important role in the pathogenesis, and after 2-3 weeks the pathology of immune complexes plays a major role. There is no clear boundary between the actual septic organ pathology and immunocomplex syndromes after the elimination of the main bacterial and microthrombotic processes. Inactivated, but non-phagated bacteria in clots can maintain their activity and cause recurrences of the disease, facilitate its transition to a chronic, more often mono-organogenic process. DIC-syndrome is almost mandatory in the pathogenesis of sepsis; The disappearance of its laboratory and clinical signs indicates successful treatment.

Thrombocytopenia and reduced coagulation can be caused not only by the consumption of platelets and coagulation factors in thrombi. In connection with infection, the formation of antibodies, immune complexes, phagocytosis (in particular, phagocytosis of neutrophils) is activated; While the enzymes of elastase, chemotripoin, are released from neutrophils. Excess of these proteolytic enzymes contributes to damage to tissues (in particular, the vascular wall), platelet lysis and some coagulation factors, which in turn leads to the development of hemorrhagic syndrome and acute respiratory distress syndrome.

The clinical picture of sepsis depends on the pathogen, the source of infection and the state of immunity. The onset of the disease can be violent with tremendous chills, hyperthermia, myalgia, hemorrhagic or papular rash, or gradual with slowly increasing intoxication and a gradual increase in body temperature. The frequent but non-specific signs of sepsis include an increase in the spleen and liver, marked sweating after a chill, severe weakness, hypodynamia, anorexia, constipation. In the absence of antibacterial therapy, sepsis, as a rule, ends with death from multiple violations of all organs and systems. Characterized by thrombosis (especially veins of the lower extremities) in combination with hemorrhagic syndrome.

With adequate antibiotic therapy, against the background of a decrease in temperature, decrease in intoxication after 2-4 weeks from the onset of the disease, arthralgia (up to the development of polyarthritis), signs of glomerurnephritis (protein, erythrocytes, urinary cylinders), symptoms of polyserositis (pleural friction noise, pericardial friction noise ) And myocarditis (tachycardia, gallop rhythm, transient systolic murmur on the apex or pulmonary artery, widening of the boundaries of relative dullness of the heart, decrease or even negativization of the T wave and downward shift of the ST segment mainly in the anterior pectoral leads). This symptomatology, arising on the background of improvement of the main indicators of septic

Process and the pathological immune complexes, should not be confused with the symptoms of actual septic, bacterial pathology. The main manifestations of the latter occur on the first days of the disease and are characterized by all signs of purulent-septic process in one or another organ (purulent myocarditis, endocarditis, variants of septic lesions of the lungs and kidneys). A decisive role in the treatment of sepsis is played by massive antibacterial therapy and fighting with DIC syndrome.

In severe DVS-syndrome, respiratory distress syndrome, multiple discoid atelectasis and unstable polymorphic shadows in the lungs due to interstitial edema are noted. Similar changes are observed in severe sepsis regardless of the pathogen and on individual radiographs are almost indistinguishable from pneumonia. However, for shadows of the inflammatory nature, persistence is characteristic, and for ephemeral vesicantial edema - ephemerality. With auscultation of the lungs, interstitial edema may be indicated by dull, small bubbling rales, crepitation.

Diagnosis. The onset of any severe inflammatory process accompanied by chills, high body temperature, at first glance, is not easy to distinguish from the onset of sepsis. However, a rapid rise in temperature to 39-40 (C, a tremendous chill, a general severe condition without pronounced monoor organ pathology, high leukocytosis with a stab shift up to 20-30%, clinical and laboratory signs of DIC syndrome are sufficient grounds for diagnosing sepsis and conducting an appropriate intensive The diagnosis of sepsis is extremely important to associate with a particular pathogen, since bacteriostatic, antiviral or antifungal therapy is strictly specific.The establishment of an etiological diagnosis is difficult and not always possible.Crop blood, the detection of specific bacterial antigens in 50-60% of cases do not give The answer to the question about the nature of the pathogen in the early days of the disease, when determining the specific tactics of treatment.The diagnosis of sepsis with the identification of the nature of the pathogen presupposes daily blood cultures, regardless of negative responses in the early days of the disease and conducted antibiotic therapy, making possible positive seeding results less and less likely . An important role in establishing the causative agent of sepsis is played by the features of the clinical picture of the disease and its first symptoms.

Staphylococcal sepsis is characterized by tremendous chills, high fever, the appearance of pain in the muscles and bones. Muscle pain can be almost ¬ morphine intensity. Usually, on the skin you can see single papules of nonhemorrhagic nature sometimes with the formation of the smallest bubbles on the top of the papule. The general condition of the patients is severe, but there is no deep general oppression, the consciousness is clear, the patients clearly tell about their feelings. On the radiographs of the lungs, numerous almost identical size and density cloudy shadows are often identified, which later merge, forming uneven foci and decay zones. At the beginning of the process, a dry cough is noted, then it becomes wet with the departure of a copious yellowish color of phlegm. The resulting abscess of the lung can break into the pleura with the development of the empyema. Myalgia is often the result of microabscesses in the muscles. In the future, the formation of multiple phlegmon, foci of osteomyelitis, liver abscess, kidney and other organs.

Meningococcal sepsis is often characterized by a violent onset with very severe intoxication, enteropathy, which in a few hours can lead to the development of shock; Characterized by progressive congestion, a rapidly onset loss of consciousness. In a number of patients, abundant polymorphic or monomorphic papular haemorrhagic eruptions appear on the skin. The finding of this rash becomes the basis for the assumption of the meningococcal nature of sepsis and the immediate administration of large doses of penicillin intravenously. Hemorrhagic eruptions testify to severe DVS-syndrome; They capture not only the skin, but also the subcutaneous tissue, so the necrosis that develops in their place can turn out to be deep enough. Heavy microthrombotic process promotes rapid formation of deep pressure sores; It also underlies the clinical picture of glomerulonephritis (up to the development of anuria) and hepatitis (a moderate rise in the level of bilirubin, hypertransminazemia against a background of liver enlargement). Severe complication of meningococcal sepsis is a bleeding in both adrenal glands (due to DIC syndrome), which causes a clinical picture of shock. Against the background of improvement in the patient's condition and normalization of temperature, meningococcal sepsis can be complicated by symmetrical gangrene (dry or moist) of the toes, and with insufficient active therapy of DIC-syndrome - and more extensive gangrene requiring amputation of the extremities. In the hemogram, hyperleukocytosis is often determined with a stab-shear shift up to 20-40%. Clinical improvement and dynamics of the blood picture may not coincide: leukocytosis and stab shift are sometimes preserved against the background of normal body temperature, which under the influence of powerful antibiotic therapy decreases for several days, and multiple organ pathology and deep necrosis remain for several weeks. Along with high leukocytosis, thrombocytosis occurs (sometimes up to 1 million or more platelets in 1 μl of blood), in particular, due to activation of colony-stimulating factors of hemopoiesis under the influence of interleukin I, produced by macrophages that process the antigen of the pathogen.

With the increase in the level of interleukin I (as an endogenous pyrogen), fever, neutrophilia, proliferation of T-helpers, the production of antibodies are associated.

Pneumococcal sepsis is characterized by the usual onset of sepsis: a tremendous chill, a rise in body temperature up to 39-40 "C. However, in these cases there is a pronounced intoxication with adynamia, but without loss of consciousness and shock. Patients respond monosyllabically to questions that quickly deplete. , Myalgia, phlegmon and other manifestations of septicemia of pneumococcal sepsis are not characteristic.The absence of a pronounced organ pathology against the background of an extremely severe general condition is noteworthy.The distinctive feature of the disease is often the preservation of a small percentage of eosinophils in the blood, while other types of bacterial sepsis are characterized by aneosinophilia.Leukocytosis in pneumococcal sepsis Moderate, but the stab shift can be expressed.Hemorrhagic syndrome is usually absent.The course of pneumococcal sepsis is not as violent as meningococcal (exceptions may be!), But the improvement of the condition under the influence of antibacterial therapy also does not occur as quickly as in meningococcal sepsis.

The first signs of adequacy of treatment are a decrease in weakness, the disappearance of chills, the appearance of appetite, although the body temperature for several days can remain elevated, only showing a tendency to decrease. Underestimation of the subjective index of improvement is very dangerous, since the absence of laboratory signs of improvement against the background of persistent febrile temperature can create an erroneous idea of ​​the ineffectiveness of antibiotic therapy, while it is penicillin (and not broad-spectrum antibiotics) that is shown in pneumococcal sepsis throughout the disease, Lasting many weeks, and sometimes months (for example, with an infected thrombus in a large vessel). The premature withdrawal of penicillin is indicated by recurrence of fever, worsening of the general condition, resumption of chills. All this does not require a change of antibiotic, and return to penicillin treatment in large doses (usual for pneumococcal and meningococcal sepsis, penicillin doses for adults amounting to 20,000,000-24,000,000 units / day should not be significantly increased, since at doses of 30,000 000-40 000 000 units / day can develop severe hemolysis, pancyolysis or hemorrhagic syndrome caused by platelet disaggregation). Peculiarity of pneumococcal sepsis is low or complete absence of bright organ manifestations of the disease, although this type of sepsis, like others, can be complicated by an immunocomplex syndrome of one kind or another.

Sepsis caused by gram-negative microorganisms (Escherichia coli, Proteus, Pseudomonas aeruginosa) occurs either in the presence of large entrance gates (postoperative abscesses in the abdominal cavity, abscesses in the small pelvis after gynecological interventions, infected thrombus in the aneurysmally dilated aorta) or with a sharp suppression of immunity (Cytostatic therapy, lymphoproliferative tumors of the blood system, acute leukemia). In the diagnosis of these forms of sepsis an important role is played by bacteriological analysis - blood culture, urine, sputum, bacterioscopy of excretions from wounds and prints of wound surfaces. One of the manifestations of Pseudomonas septicemia (sometimes staphylococcal) is necrotic hemorrhage: rashes (sometimes single) of a deep dark red, almost black color, surrounded by a dark red shaft and rising above the skin surface. These sometimes painful (especially in the beginning) education gradually grow; Body temperature remains febrile; There are child screenings at other sites of the skin and in internal organs (found during pathoanatomical research). Necrotic hemorrhages practically do not give in to usual kinds of antibacterial therapy because of surrounding dense thrombotic shaft, but inside these formations there is an active pathogenic flora. The mechanism of necrotic hemorrhage formation seems to be close to the pathogenesis of nome and gangrene, in which the focus of necrosis is played by a focally growing area of ​​thrombosis: the infection provokes thrombus formation, blood clots form a nutrient medium for the growth of microorganisms and block the entry of antibiotics into the necrotic focus. The process turns out to be self-sustaining due to depletion of the fibrinolysis system. The main means of breaking this vicious circle is the local application of dimethylsulfoxide with an antibiotic against the background of usual antibacterial therapy and increasing fibrinolytic activity of the blood with the help of massive transfusions of fresh frozen plasma.

Sepsis caused by Pseudomonas aeruginosa, against immunodepression (with cytostatic therapy, tumors of the blood system) is characterized by extreme severity and rapidly developing shock. The same sepsis that occurred with normal blood levels as a result of the breakthrough of infection from an infected thrombus, can proceed torpidly; The condition of patients worsens gradually; Antibiotic therapy has some positive, but unstable effect. In general, sepsis due to gram-negative microflora, without entrance gates, with the normal composition of leukocytes and without the use of immunosuppressants is highly unlikely. For sepsis, the rapid development of shock (sometimes literally within 2-3 hours of the appearance of febrile temperature).

Diagnosis of sepsis caused by Gram-negative microflora in hematological and oncological hospitals often falls on the shoulders of the doctor on duty, who nevertheless before the beginning of antibacterial therapy (simultaneously with the first administration of the antibiotic) should take the blood for seeding in any sterile closed dishes and put in a thermostat at 37 "C. In the diagnosis of sepsis, any sign that allows assessing the nature of the pathogenic flora should not be neglected.So if the source of sepsis is some festering cavity (empyema of the pleura, intestinal abscess, etc.), then the nature of microflora is trying to determine to a certain extent V The clinical sign of the change of pathogen against the background of the current septic process is the change in the clinical picture of the disease: on the background of a progressive improvement in the state, the temperature of the tep suddenly rises, chills appear, leukocytosis increases, and a pronounced staboconversion is again detected .This is also possible due to the formation of a septicopyemic cavity. Therefore, simultaneously with the search for a new pathogen, it is necessary to exclude the presence of an abscess of internal organs by all available means (intrahepatic abscess, carbuncle of the kidney, etc.).

Sepsis caused by herpes viruses occurs almost exclusively against the background of severe immunosuppression in lymphoproliferative diseases (including acute limfoblastic T-cell leukemia), and lymphogranulomatosis. Diagnosis of generalization of the herpes zoster virus is not difficult when the process begins with a small characteristic segmental rash. Then the rashes spread all over the skin and appear on the mucous membrane of the mouth, trachea, bronchi, esophagus, vocal cords. Similarly, sepsis caused by the varicella-zoster virus, and less often by the herpes simplex virus, can also occur. In the detailed picture, all three processes are virtually indistinguishable. Damage to the surface of the rashes, removal of crusts (this can not be done!) May be accompanied by secondary infected elements of the rash and the development of usually staphylococcal sepsis.

Treatment of sepsis should be primarily pathogenetic. Since the massive nature of the infection plays a crucial role in the development of sepsis, unlike any other infection, the presence of microorganisms in the blood and all tissues in combination with the expressed disseminated intravascular coagulation, the therapy is directed against two components of the process - infection and DIC syndrome . Patients with sepsis should be hospitalized immediately if they suspect him in the intensive care unit or resuscitation. Hemorrhages in the adrenal glands, gangrene of the extremities, irreversible changes in the internal organs are a consequence of the belated pathogenetic therapy of the patient with sepsis.

Following the diagnosis, blood is taken from the veins for culture, for biochemical studies (bilirubin, prothrombin, transaminases, LDH, creatinine, protein fractions) and for the analysis of the clotting system (fibrinolytic activity, protamine sulfate and ethanol tests, fibrinogen degradation products). In the study of blood, a count of platelets and then of reticulocytes is mandatory. Immediately after taking blood for various studies through the same needle, an antibiotic is injected into the vein, according to the nature of the infection, but at the maximum possible doses. In the presence of severe signs of DIC syndrome (in particular, a profuse rash, especially of a hemorrhagic nature), myalgia and tenderness of the muscles during palpation, polymorphic shadows of the interstitial pulmonary edema or more or less the same shades of hematogenous dissemination of the infection on the chest X-ray, immediately begin plasmapheresis . Remove about 1.5 liters of plasma, replacing it by about 2/3 the corresponding volume of fresh frozen plasma. In severe sepsis, the volume of freshly frozen plasma poured can exceed the volume of plasma removed; In this case, at least 2 liters of fresh frozen plasma should be introduced.

In addition to the above signs of DIC syndrome, it is necessary to take into account the symptom of thrombosis of the needle in venipuncture, as well as rapid thrombosis after digging the finger for blood analysis. Against the background of sepsis, these signs are sufficient for a reliable diagnosis of DIC syndrome. Following the plasmapheresis, and if necessary and during it, heparin is administered at a dose of 20 000-24 000 U / day for adults. Heparin is injected intravenously drip, either continuously or hourly. Increase the intervals between doses of heparin, at least on the first day of treatment, should not be. The presence of hemorrhagic syndrome is not a contraindication, but an indication for the treatment with heparin. If plasmapheresis is not feasible, it is necessary to introduce fresh-frozen plasma in the same volume as in plasmapheresis. In the first days of treatment, subcutaneous and intramuscular injections are undesirable.

With arterial hypotension, sympathomimetics is used; With persistent lowering of arterial pressure, hydrocortisone or prednisolone is injected intravenously at a dose sufficient to stabilize the patient's condition, after which steroid hormones are canceled on the same day, and with prolonged use (if there is no hemorrhage to the adrenal glands, prolonged glucocorticoid therapy is highly undesirable) - within 2-3 days. By itself, arterial hypotension does not serve as a contraindication to plasmapheresis, which in this case begins with the introduction of IV 500-1000 ml of fresh frozen plasma and carried out in a small volume (500-800 ml of the plasma removed).

For prolonged and numerous intravenous infusions, there is usually a need for catheterization of one of the peripheral or less frequently central veins. It should be remembered that delayed body temperature rises (after several days of its persistent decline) may result from thrombosis of the vein near the catheter, as well as infection of the thrombus or the adjacent subcutaneous tissue; The skin in this place is hyperemic. In such cases, the catheter is either completely removed or injected into another vein.

Antibacterial therapy for sepsis is determined by the type of suspected or established pathogen. If neither clinical nor laboratory signs allow to establish with any certainty the etiologic factor, a course of so-called empiric antibacterial therapy is prescribed: gentamicin (160-240 mg / day) in combination with cephaloridine (cephrine) or cefazolin (kefzol) in a dose 4 g / day IV. To evaluate the effectiveness of antibiotic therapy on the foci of other therapeutic measures is necessary to improve the subjective state of the patient, stabilize blood pressure, reduce body temperature, disappear chills, reduce the number of old or no new rashes on the skin. The laboratory evidence of the efficacy of antibiotics includes a decrease in the percentage of stab elements in the blood formula. A distinct weighting of the condition for all the listed indicators within 24-48 h and worsening of the patients' well-being on the next day after the beginning of antibacterial therapy testify to the ineffectiveness of the selected antibiotics and the need to replace them.

The following scheme of empirical antibacterial therapy suggests that sepsis is caused not by staphylococcus, which is not called an E. coli, is characterized by the absence of organ pathology and septicopyemia, rapid development of shock (sometimes literally within 2-3 hours of febrile temperature).

Diagnosis of sepsis caused by Gram-negative microflora in hematological and oncological hospitals often falls on the shoulders of the doctor on duty, who nevertheless before the beginning of antibacterial therapy (simultaneously with the first administration of the antibiotic) should take the blood for seeding in any sterile closed dishes and put in a thermostat at 37 "C. In the diagnosis of sepsis, any sign that allows assessing the nature of the pathogenic flora should not be neglected.So if the source of sepsis is some festering cavity (empyema of the pleura, intestinal abscess, etc.), then the nature of microflora is trying to determine to a certain extent By smell.

The clinical sign of a pathogen change in the background of the current septic process is the change in the clinical picture of the disease: on the background of progressive improvement in the state, the temperature of the tep suddenly rises, chills appear, leukocytosis increases, and a pronounced stab shift is again detected. Similar changes are possible due to the formation of a septicopyemic cavity. Therefore, simultaneously with the search for a new pathogen, it is necessary to exclude the presence of an abscess of internal organs by all available means (intrahepatic abscess, carbuncle of the kidney, etc.).

Sepsis caused by herpes viruses occurs almost exclusively against the background of severe immunodepression with lymphoproliferative diseases (including acute lymphoblastic T-cell leukemia), and lymphogranulomatosis. Diagnosis of generalization of the herpes zoster virus is not difficult when the process begins with a small characteristic segmental rash. Then the rashes spread all over the skin and appear on the mucous membrane of the mouth, trachea, bronchi, esophagus, vocal cords. Similarly, sepsis caused by the varicella-zoster virus, and less often by the herpes simplex virus, can also occur. In the detailed picture, all three processes are virtually indistinguishable. Damage to the surface of the rashes, removal of crusts (this can not be done!) May be accompanied by secondary infected elements of the rash and the development of usually staphylococcal sepsis.

Treatment of sepsis should be primarily pathogenetic. Since the massive nature of the infection plays a crucial role in the development of sepsis, unlike any other infection, the presence of microorganisms in the blood and all tissues in combination with the expressed disseminated intravascular coagulation, the therapy is directed against two components of the process - infection and DIC syndrome . Patients with sepsis should be hospitalized immediately if they suspect him in the intensive care unit or resuscitation. Hemorrhages in the adrenal glands, gangrene of the extremities, irreversible changes in the internal organs are a consequence of the belated pathogenetic therapy of the patient with sepsis.

Following the diagnosis, blood is taken from the veins for culture, for biochemical studies (bilirubin, pro-thrombin, transaminases, LDH, creatinine, protein fractions) and for the analysis of the clotting system (fibrinolytic activity, protamine sulfate and ethanol tests, fibrinogen degradation products). In the study of blood, a count of platelets and then of reticulocytes is mandatory. Immediately after taking blood for various studies through the same needle, an antibiotic is injected into the vein, according to the nature of the infection, but at the maximum possible doses. In the presence of severe signs of DIC syndrome (in particular, a profuse rash, especially of a hemorrhagic nature), myalgia and tenderness of the muscles during palpation, polymorphic shadows of the interstitial pulmonary edema or more or less the same shades of hematogenous dissemination of the infection on the chest X-ray, immediately begin plasmapheresis . Remove about 1.5 liters of plasma, replacing it by about 2/3 the corresponding volume of fresh frozen plasma. In severe sepsis, the volume of freshly frozen plasma poured can exceed the volume of plasma removed; In this case, at least 2 liters of fresh frozen plasma should be introduced.

In addition to the above signs of DIC syndrome, it is necessary to take into account the symptom of thrombosis of the needle in venipuncture, as well as rapid thrombosis after digging the finger for blood analysis. Against the background of sepsis, these signs are sufficient for a reliable diagnosis of DIC syndrome. Following the plasmapheresis, and if necessary and during it, heparin is administered at a dose of 20 000-24 000 U / day for adults. Heparin is injected intravenously drip, either continuously or hourly. Increase the intervals between doses of heparin, at least on the first day of treatment, should not be. The presence of hemorrhagic syndrome is not a contraindication, but an indication for the treatment with heparin. If plasmapheresis is not feasible, it is necessary to introduce fresh-frozen plasma in the same volume as in plasmapheresis. In the first days of treatment, subcutaneous and intramuscular injections are undesirable.

With arterial hypotension, sympathomimetics is used; With persistent lowering of arterial pressure, hydrocortisone or prednisolone is injected intravenously at a dose sufficient to stabilize the patient's condition, after which steroid hormones are canceled on the same day, and with prolonged use (if there is no hemorrhage to the adrenal glands, prolonged glucocorticoid therapy is highly undesirable) - within 2-3 days. By itself, arterial hypotension does not serve as a contraindication to plasmapheresis, which in this case begins with the introduction of IV 500-1000 ml of fresh frozen plasma and carried out in a small volume (500-800 ml of the plasma removed).

For prolonged and numerous intravenous infusions, there is usually a need for catheterization of one of the peripheral or less frequently central veins. It should be remembered that delayed body temperature rises (after several days of its persistent decline) may result from thrombosis of the vein near the catheter, as well as infection of the thrombus or the adjacent subcutaneous tissue; The skin in this place is hyperemic. In such cases, the catheter is either completely removed or injected into another vein.

Antibacterial therapy for sepsis is determined by the type of suspected or established pathogen. If neither clinical nor laboratory signs allow to establish with any certainty the etiologic factor, a course of so-called empirical antibacterial therapy is prescribed: gentamicin (160-240 mg / day) in combination with cephaloridine (cephrine) or cefazolin (kef-ash) In a dose of 4 g / day IV. To evaluate the effectiveness of antibiotic therapy on the foci of other therapeutic measures is necessary to improve the subjective state of the patient, stabilize blood pressure, reduce body temperature, disappear chills, reduce the number of old or no new rashes on the skin. The laboratory evidence of the efficacy of antibiotics includes a decrease in the percentage of stab elements in the blood formula. A distinct weighting of the condition for all the listed indicators within 24-48 h and worsening of the patients' well-being on the next day after the beginning of antibacterial therapy testify to the inefficiency of the selected antibiotics and the need to replace them.

The following scheme of empirical antibacterial therapy suggests that sepsis is caused not by staphylococcus, not by E. coli and not by meningococcus (meningococcal sepsis with ineffective antibacterial treatment usually manifests itself as a hemorrhagic rash). The smallest lesion of the internal organs is usually observed in pneumococcal sepsis. In this regard, it is advisable to replace cephalosporins with large doses of penicillin (20,000,000-24,000,000 units / day IV for 8 or IV injections continuously), while continuing treatment with gen-tamycin.

If the results of the study allow us to consider that sepsis is caused by gram-negative microorganisms, the patient is prescribed carbenicillin (20-30 g / day B / in drip or jet for 6-8 injections), while continuing to use gentamicin. Since carbenicillin belongs to disaggregating drugs (i.e., interferes with platelet aggregation), manifestations of a mild hemorrhagic syndrome are possible - more than usual, severe hemorrhages in the area of ​​injections, mechanical injuries. If these antibiotics are effective, the hemorrhagic cider itself can not be regarded as an indication for their withdrawal; It is only necessary to strictly exclude other disaggregating agents (primarily non-steroidal anti-inflammatory drugs) from complex therapy.

Treatment of established or suspected pneumococcal or meningococcal sepsis involves intravenous administration of penicillin in the above doses. Практически во всех случаях неэффективности пенициллинотерапии у этих больных речь идет о неправильно поставленном этиологически диагнозе. В оценке эффективности антибактериальной терапии этих двух видов сепсиса важно обращать внимание на субъективное улучшение самочувствия) на стабилизацию процесса, отсутствие ухудшения состояния на протяжении нескольких дней, а не только на температуру тела. Все эти признаки говорят в пользу эффективности проводимой терапии, служат достаточным основанием для сохранения проводимого лечения неизменным, без какой-либо суеты и необоснованной смены антибиотиков. Поскольку возникновения устойчивых к пенициллину штаммов среди пневмококков и менингококков практически не наблюдается, нет оснований для отмены этого антибиотика на протяжении всего курса лечения (не менее 3 нед) при условии их эффективности.

Особенно трудна антибактериальная терапия сепсиса, возникшего на фоне предшествующей иммунодепрессии. В этих случаях антибиотики или сульфаниламиды нередко оказывают временный эффект - температура тела снижается, самочувствие улучшается (в этих случаях органные проявления сепсиса часто незначительны), но затем вдруг вновь начинаются лихорадка, озноб и т. п. В анамнезе у таких больных нередко большой спектр применяемых антибиотиков, оказывавших временный положительный эффект. В этих случаях показана терапия препаратами гамма-глобулинов, вводимых внутривенно (в частности, эндобулин в дозе 1-2 г на 10 кг массы тела 1 раз в 7-10 дней, а при тяжелом течении сепсиса 2 раза в неделю; эндобулин нежелательноиспользовать перед плазмаферезом и в те дни, когда осуществлялись трансфузии плазмы, эритроцитной массы, альбумина и других белковых препаратов).

При стафилококковом сепсисе терапию целесообразно начинать с применения антибиотика из группы цефалоспори-нов вместе с гентамицином (см. выше). Если эффект недостаточен, гентамицин можно заменить амикацином (500 мг 2-3 раза в день) или тобрамицином (80 мг 2-3 раза в день). Даже при незначительной почечной недостаточности цефалоспорины могут оказаться резко нефротоксичными (они выводятся почками). Нефротоксичны и применяемые в этой схеме амингликозиды (гентамицин и др.). Поэтому терапия указанными антибиотиками должна сопровождаться постоянным (2 раза в неделю) контролем уровня креатинина в крови, анализами мочи и определением диуреза.

Ухудшение функции почек, требующее либо отмены антибиотиков данного ряда, либо уменьшения их дозы, просчитываемой по клиренсу креатинина, проявляется уменьшением диуреза (вплоть до анурии, когда необходим массивный немедленный плазмаферез) и нарастанием уровня креатинина за пределы его верхней границы нормы. Длительность антибактериальной терапии при сепсисе определяется существованием основных проявлений болезни (в том числа иммунокомплексных); обычно отрицательные результаты посевов крови не имеют значения в качестве критерия отмены антибиотиков. Антибактериальную терапию следует продолжать не менее 2-3 нед при самом благоприятном течении болезни. При затянувшемся процессе, появлении признаков септического эндокардита, септикопиемических очагов, остеомиелита антибактериальную терапию продолжают много месяцев.

Таким образом, длительная направленная антибактериальная терапия, гепарин, свежезамороженная плазма, плазмаферез -основные способы лечения сепсиса, направленные на уничтожение возбудителя, активацию фагоцитоза в селезенке и факторов гуморального иммунитета, опсонизацию бактерий, подавление кининов, введение антиагрегантного фактора плазмы и плазминогена, необходимого для активации фибринолиза. Плазмаферез усиливает выведение разрушенных клеток, бактерий, активирует фагоцитарную функцию селезенки, которая при сепсисе, как правило, оказывается заблокированной.