Sepsis

Sepsis, severe sepsis and septic shock are inflammatory conditions developing with a generalized bacterial infection. With severe sepsis and septic shock, a critical decrease in tissue perfusion is observed. The main causes of sepsis are gram-negative microorganisms, staphylococci and meningococci. Often the disease begins with chills, fever, hypotension and oliguria. Acute multiorgan insufficiency may develop. Treating sepsis is aggressive infusion therapy, antibiotics, supportive therapy, exercise of control glucose levels, administration of glucocorticoids and activated protein C.

Sepsis has been known since ancient times as "putrefaction" (Avicenna).

Currently, sepsis means complications of purulent process, inflammatory complications of surgical interventions and traumatic injuries, in which the severity of systemic manifestations is directly proportional to the prevalence of the inflammatory process or the lesion area, i.e. There is a direct correlation between the reaction of the macroorganism and the focus of infection.

Sepsis is characterized by the continuous or periodic inflow into the blood of microorganisms from a purulent focus, microbial or tissue intoxication with the development of severe polyorganic disorders and often the formation of new foci of purulent inflammation in various organs and tissues.

A characteristic feature of sepsis is the loss of the body's ability to fight off pathogens outside the infectious focus.

The number of patients with sepsis has increased 4-6 times in recent years.

Mortality in sepsis remains high and is 20-69%.

[1], [2], [3],

What causes sepsis?

In most cases, septic shock is caused by nosocomial gram-negative rods or Gram-positive cocci, often in patients with immune system disorders and chronic diseases. Rarely, the cause is Candida or other fungi. A unique form of shock caused by staphylococcal and streptococcal toxins is called toxic shock.

Septic shock is more common in neonatology, in patients older than 35 years and pregnant. Predisposing factors are diabetes, cirrhosis, leukopenia, especially oncological diseases or cytotoxic drugs; presence of artificial materials used for invasive diagnostic or therapeutic procedures, including endotracheal tubes, vascular and urinary catheters, drainage tubes, etc .; previous treatment with antibiotics or glucocorticoids. Sources of infection can be the lungs and urinary, biliary and gastrointestinal tract.

Pathophysiology of sepsis

The pathogenesis of sepsis is not fully understood. Bacteria or their components (eg, toxin) cause the activation of tissue macrophages with the product of proinflammatory mediators, including tumor necrosis factor (TNF) and interleukin 1 (IL-1). These cytokines promote the activation of the endothelium, increase the porosity of the vascular wall and extravasation of neutrophils and macrophages, simultaneously activate the system of coagulation and anticoagulation, on the surface of the damaged endothelium there is the formation of microthrombi consisting of platelets and fibrin. In addition, cytokines contribute to the release of a large number of other mediators, including leukotrienes, lipoxygenase, histamine, bradykinin, serotonin and IL-2. They are countered by anti-inflammatory mediators, such as IL-4 and IL-10, as a result of activation of the feedback mechanism.

In the initial phase, arteries and arterioles expand, peripheral arterial resistance decreases; cardiac output, as a rule, increases. This state is described as a "warm shock". Later cardiac output may decrease, blood pressure drops (against the background of the same or increased peripheral resistance) and there are characteristic signs of shock.

With an increased cardiac output, the vasoactive mediators cause a shunting of blood flow around the capillaries (the effect of redistribution). Deterioration of microcirculation as a result of shunting of blood and formation of microthrombi leads to a decrease in the delivery of oxygen and nutrients, a violation of the removal of carbon dioxide and metabolic products. Decreased perfusion causes dysfunction, and sometimes damage to one or more organs, including the kidneys, lungs, liver, brain and heart.

Coagulopathy develops as a result of intravascular coagulation with the consumption of most coagulation factors, in addition, acute fibrinolysis can develop.

Sepsis - Causes and pathogenesis

Symptoms of sepsis

When sepsis is usually observed fever, tachycardia and tachypnea; BP remains normal. There are signs of a generalized infectious process. With the development of severe sepsis or septic shock, the first symptom may be a violation of mental status. BP usually falls, the skin becomes paradoxically warm, oliguria appears (less than 0.5 ml / kg / h). Later, the limbs become cool and pale with peripheral cyanosis and marbling, then signs of organ damage appear.

Sepsis - Symptoms

Classification of sepsis

There is a classification of sepsis, based on the severity of its course.

Sepsis is a generalized infection, accompanied by a response from the body, which is referred to as the syndrome of a systemic inflammatory reaction (SSRS). SSRM is an acute inflammatory reaction with systemic manifestations, caused by the release into the bloodstream of numerous endogenous inflammatory mediators. SSRM can also develop with pancreatitis and trauma, including burns. Diagnosis of SSER is based on the presence of two or more of the following criteria:

• Temperature> 38 ° C or <36 ° C
• Heart rate> 90 beats / min
• Respiratory rate> 20 times / min or Ra-CO2 32 mm Hg. Art.
• The number of leukocytes is> 12,000 cells / μl or <4000 cells / μl, or> 10% of immature forms.

Sepsis in the USA

Category	Number of cases	Mortality (%)	Number of deaths per year
Sepsis	400 000	15	60,000
Severe sepsis	300 000	20	60,000
Septic shock	200 000	45	90 000

At the moment, these criteria are considered additional, but not accurate enough to be diagnostic.

Severe sepsis is sepsis, which is accompanied by signs of the defeat of at least one organ. Cardiovascular failure is manifested by hypotension, respiratory failure - hypoxemia, renal - oliguria and hematologic disorders - coagulopathy.

Septic shock is a severe sepsis with organ hypoperfusion and hypotension, the correction of which is not achieved in response to initial vollemic support.

Historically, the following classifications have been and are in practice used.

1. Depending on the root cause, distinguish:
   • primary, or cryptogenic, sepsis (is extremely rare), when the cause of sepsis remains unknown (do not find the entrance gate and purulent focus);
   • secondary sepsis, the cause of it - the presence of any purulent focus; Depending on the entrance gate of the infection, there are gynecological, surgical, urological, traumatological, odontogenic sepsis, etc .; surgical sepsis is a serious common disease that occurs against the background of an existing local foci of infection and requires surgical intervention and general intensive treatment.
2. According to the type of current, they distinguish:
   • fulminant - develops within 1-3 days after infection (it is necessary to distinguish lightning sepsis from septic shock - a complication that can occur in any form and duration of purulent process);
   • acute - develops within 4 days to 2 months from the introduction of infection;
   • subacute - from 2 to 6 months;
   • chronic sepsis.

Some authors also distinguish recurrent sepsis, characterized by a change in the periods of exacerbations (when all symptomatology is pronounced) and periods of remission (when it is not possible to reveal any noticeable symptomatology).

3. Depending on the features of the clinical picture, the following forms of sepsis are distinguished:
   • septicemia (sepsis without metastases);
   • septicopyemia (sepsis with metastases).

According to the classification of the international conciliation conference (1991) distinguish purulent-resorptive fever (sepsis) and acute staphylococcal septicopyemia.

In our country, the classification of sepsis, proposed by the international conciliation conference of 1991, did not receive proper recognition, apparently because of the terminological problems. Currently, we use the following terms more often.

"The first, often encountered option is sepsis as a complication of surgical infection, when" the worse locally (in a purulent focus), the worse the overall condition of the patient. "

In this situation, sepsis essentially reflects a certain degree of severity of the patient's condition. In such cases, when formulating the diagnosis, sepsis should occupy an appropriate place: for example, pancreatic necrosis, retroperitoneal phlegmon, sepsis. This procedure determines the diagnostic and therapeutic tactics - the priority is not the attempts of immunomodulation and extracorporeal detoxification, but adequate drainage of the purulent focus.

The second option - sepsis as a rare disease - septicopyemia, when the determining criterion is the emergence of metastatic pyemic) purulent foci. Then, in the formulation of the diagnosis, after the word "sepsis", the designation of the primary focus of infection followed by the enumeration of the localization of pemic (secondary) purulent foci should follow. "

[4], [5], [6],

Diagnosis of sepsis

The diagnosis of sepsis is given to patients with the presence of SSRS or organ dysfunction on the background of a generalized infectious process. In patients with signs of systemic inflammatory response, it is necessary to focus on finding the source of the infectious process according to anamnesis, physical and laboratory examination, including urinalysis (especially if there is a urinary catheter), blood and other physiological fluids. Severe sepsis in the blood increased the level of procalingcin and C-reactive protein.

In addition, it is necessary to exclude other causes of shock (hypovolemia, myocardial infarction). Even in the absence of myocardial infarction, hypoperfusion can lead to changes in the ECG by the type of ischemia.

It is necessary to perform a general blood test (OAK), arterial blood gases, chest X-ray, determination of blood electrolytes, lactate or sublingual PCO2, liver function. At the onset of septic shock, the number of leukocytes can decrease less than 4000 / μl, and the number of immature forms of neutrophils increases to 20%. After 1-4 hours the situation changes, and as a rule, there is a significant increase in the total number of leukocytes greater than 15,000 / μL and immature forms of neutrophils more than 80% (with the dominance of young forms). Early decrease in the number of platelets below 50 000 / μl.

Early respiratory disorders develop in the form of hyperventilation with respiratory alkalosis (low PaCO2 and an increase in arterial pH), aimed at partial compensation of lactic acidosis. With the increase of shock, metabolic acidosis is increased. Early respiratory failure leads to hypoxemia with PaO2 less than 70 mm Hg. Art. On the roentgenogram of the chest can be diffuse infiltrative shadows. Blood urea nitrogen and creatinine usually increase as a result of renal failure. Bilirubin and transaminases can be increased even in the absence of signs of liver failure.

Up to 50% of patients with severe sepsis have a relative adrenal insufficiency (normal or slightly elevated cortisol level, which does not increase significantly in response to further stress or the introduction of exogenous ACTH). Adrenal function can be assessed by serum cortisol at 8 am; a level of less than 5 mg / dl is considered inadequate. On the other hand, cortisol can be measured before and after injection of 250 μg of synthetic ACTH; an increase of less than 9 μg / dl is considered insufficient. Most specialists recommend prescribing glucocorticoid replacement therapy without conducting a laboratory test. Usually, with severe sepsis and septic shock, glucocorticoid replacement therapy is used: 100 mg of water-soluble hydrocortisone after 8 hours for 2-4 days.

Hemodynamic measurements using a catheter in the pulmonary artery may be required when the type of shock remains unclear or large infusion volumes are required (more than 4-5 liters of crystalloids in 6-8 hours). Unlike hypovolemic, septic shock is characterized by a normal or increased cardiac output with reduced peripheral vascular resistance. Deviations in central venous pressure (CVP) or pulmonary wedge pressure (DZLA) are unlikely, which is usually observed with hypovolemic or cardiogenic shock. Echocardiography can be useful in assessing the function of the heart.

Sepsis - Diagnosis

[7], [8]

Treatment of sepsis

Overall mortality in septic shock is reduced and averages 40% (from 10 to 90%). An adverse outcome is most often associated with the limited ability to initiate an early onset of intensive care (within 6 hours) because of problems associated with the diagnosis of sepsis. With severe lactic acidosis and decompensated metabolic acidosis, especially in combination with multiple organ failure, septic shock is most likely to be irreversible and lead to death.

Treatment of patients with septic shock is usually performed in the intensive care unit. They need constant monitoring of blood pressure, CVP, pulse oximetry, regular examination of arterial blood gases, glycemia, lactatemia, blood electrolytes, renal function and, possibly, sublingual PCO ₂. Diuresis is the best indicator of renal perfusion, its measurement is usually performed with the help of a permanent catheterization of the bladder.

Infusion of saline should be done until the CVP rises to 8 mm Hg. Art. (10 cm H2O) or DZLA up to 12-15 mm Hg. Art. Oliguria with hypotension is not a contraindication for active infusion therapy. Volumes of injected fluid can significantly exceed the volume of circulating blood (BCC) and reach 10 liters in 4-12 hours. DZLA or echocardiography can detect violations of left ventricular function or the initial stage of development of pulmonary edema due to fluid overload.

If hypotension persists after CVP and DZLA have reached the target, dopamine is connected in order to raise blood pressure to at least 60 mm Hg. Art. If the required dose of dopamine exceeds 20 mcg / kg / min, another vasopressor (usually norepinephrine) should be added. It should be borne in mind that vasoconstriction caused by high doses of dopamine and norepinephrine contributes to an increased risk of organ hypoperfusion and acidosis, and it has not been proven that the use of these drugs improves the outcome of patients with septic shock.

Oxygen is supplied through a mask or nasal cannula. The need for endotracheal intubation and mechanical ventilation of the lungs may occur with the development of respiratory failure.

Parenteral administration of antibiotics begins after blood, other biological fluids and the contents of the wounds are taken for coloring on Gram and for sowing. The rapid onset of empirical therapy is very important and can save a patient's life. The choice of antibiotic is based on information about the probable source of infection, clinical data, the microflora characteristic of the department, its sensitivity to antibiotics obtained during local monitoring of the circulating flora.

With an unknown pathogen, one of the options for empiric therapy involves the use of gentamicin or tobramycin 5.1 mg / kg intravenously intravenously once a day in combination with third generation cefalosporin (cefotaxime 2 g at 6-8 h or ceftriaxone 2 g once daily if the probable pathogen is Pseudomonas - ceftazidime 2 g intravenously after 8 hours). A combination of ceftazidime and ciprofloxacin is possible. Monotherapy with maximum therapeutic doses of ceftazidime (2 g intravenously after 8 h) or imipenem (1 g intravenously after 6 h) is possible, but not recommended.

Vancomycin should be used if infectious agents can be resistant to staphylococci or enterococci. With the abdominal source of infection, a drug effective against anaerobes (metronidazole) is prescribed. After receiving the results of seeding and sensitivity, correction of antibacterial therapy may be required. The use of antibiotics continues for several days after the removal from the shock and the fading of the infectious process.

Abscesses must be drained, and necrotic tissues (for example, intestinal infarction, gangrenous-altered gallbladder, abscesses of the uterus) are surgically removed. Deterioration of the patient's condition against the background of antibacterial therapy is an occasion to search for an unsanitary purulent focus.

Normalization of glycemia and its strict control improve the outcome in critically ill patients, even in patients who do not suffer from diabetes mellitus. The prolonged infusion of intravenous insulin (1-4 U / h of simple insulin) should provide glycemia at the level of 80-110 mg% (4.4-6.1 mmol / l). This technique involves the frequent determination (i.e., every 1-4 hours) of the plasma glucose level.

Therapy with glucocorticoids gives positive results. Often used substitution therapy, rather than pharmacological doses of glucocorticoids. One of the protocols recommends hydrocortisone 50 mg intravenously every 6 hours with the addition of fludrocortisone inside 50 μg once a day for the period of hemodynamic instability and another three days after hemodynamic stabilization.

Activated Protein C (drotrekogin-a) - a recombinant drug with fibrinolytic and anti-inflammatory activity in early use in the treatment of severe sepsis and septic shock has been shown to be effective, but only in patients at high risk of death, whose severity was assessed on the APASHEII scale> 25 points. The dosage is 24 mcg / kg / h, it is used as a continuous infusion for 96 hours. Since the main complication of this drug is bleeding, it is contraindicated in patients who had previously undergone (less than 3 months ago) hemorrhagic stroke, operations on the spinal cord and brain (less than 2 months ago), severe trauma with the threat of bleeding, as well as patients with neoplasms of the CNS. Evaluation of the risk-effect ratio is also required in patients with severe bleeding (eg, thrombocytopenia, recent gastrointestinal and bleeding from other parts of the intestine receiving heparin, aspirin and other anti-coagulants).

Other areas of treatment for severe sepsis are the fight against hyperthermia and early treatment of renal failure (eg, prolonged veno-venous hemofiltration).

Clinical studies of monoclonal antibodies to lipid A of endotoxin fraction of Gram-negative bacteria, anti-leukotrienes, antibodies to tumor necrosis factor did not show their effectiveness.

Sepsis - Treatment