Sepsis treatment protocol

The treatment of sepsis was relevant during the entire period of study of this pathological condition. The number of methods used to treat it is enormous. In part, this can be explained by the heterogeneous nature of the septic process.

The decisive shifts in the treatment technique occurred after consistent definitions of sepsis, severe sepsis and septic shock were accepted. This allowed different researchers to speak the same language using the same concepts and terms. The second most important factor was the introduction of the principles of evidence-based medicine into clinical practice. Two of these circumstances made it possible to develop scientifically based recommendations for the treatment of sepsis, published in 2003 and called the "Barcelona Declaration". It announced the establishment of an international program known as the "Movement for effective treatment of sepsis" (Surviving sepsis campaign).

The proposed methodological recommendations are based on an analysis of the results of clinical studies carried out by experts from 11 leading world professional associations and distributed according to the level of their evidence

In accordance with the guidelines, the following activities are proposed.

[1], [2], [3], [4], [5], [6], [7], [8], [9], [10], [11], [12]

Microbiological examination

All samples for microbiological examinations are taken immediately upon admission of the patient, before antibiotic treatment begins. At least two blood samples should be taken. One sample of blood is taken by puncture of the peripheral vein, and the second - from the central venous catheter (if installed earlier). Microbiological tests also send samples of physiological liquids (urine, if a urinary catheter is installed or there are good reasons for excluding the possibility of infection of the urinary system), the secret of the bronchial tree, wound detachment and other samples in accordance with the clinical picture of the leading pathology.

Primary intensive care

Are directed on achievement in the first 6 h of intensive treatment (actions begin to be carried out immediately after diagnosis) of the following values of the parameters:

• CVP 8-12 mmHg;
• mean BP> 65 mmHg;
• amount of urine output> 0.5 ml / (kghh);
• saturation of mixed venous blood> 70%.

If the transfusion of various infusion media fails to achieve the elevation of CVP and the level of saturation of mixed venous blood to the indicated figures, it is recommended that:

• transfusion of erythromass to a level of hematocrit equal to 30%;
• infusion of dobutamine in a dose of 20 mcg / kg per minute.

The implementation of this set of measures makes it possible to reduce the lethality from 49.2 to 33.3%.

Antibacterial treatment

Treatment with broad-spectrum antibiotics begins within the first hour after diagnosis. The choice of an antibacterial drug is based on the patient's examination data with an assessment of the probable pathogen and taking into account the data of the local monitoring of the microflora of the hospital (department).

Depending on the results of microbiological studies obtained after 48-72 hours, the scheme of antibacterial drugs used is revised to select a narrower and more targeted treatment.

[13], [14], [15], [16], [17],

Controlling the source of infection

Each patient with signs of severe sepsis should be carefully examined to detect the source of the infectious process and to carry out appropriate source control measures, which consist of three groups of surgical interventions:

1. Drainage of the abscess cavity. An abscess is formed by the initiation of an inflammatory cascade and the formation of a fibrin capsule surrounding a liquid substrate consisting of necrotic tissues, polymorphonuclear leukocytes and microorganisms and is well known to clinicians as pus. Drainage of the abscess is an obligatory procedure in the treatment, however, the technique of its carrying out undergoes a certain evolution. The main trend in recent years has been the drainage of the abscess using ultrasound equipment or CT, as well as with the help of endovideosurgical interventions. The use of modern navigation technology significantly reduces the risk of surgery due to the reduction of tissue trauma.
2. Secondary surgical treatment (necrotomy). Removal of necrotic altered tissues involved in the infectious process is one of the main tasks in achieving control over the source. Only after performing a full surgical treatment, it is possible to achieve control over the local infectious process, and consequently, to reduce the severity of the systemic reaction. Despite the fact that the manifestations of the effects of the "cytokine storm" can be expressed to a large extent, and sometimes determine an unfavorable outcome, the operation to remove necrotic infected tissues should be considered as a priority task. The question remains unclear about the extent of necrectomy in the absence of an infectious process in devitalized tissues. Expansion of the scope of operative intervention is contraindicated in the absence of demarcation.
3. Removal of foreign bodies that support (initiate) the infectious process. In modern reconstructive and replacement surgery, various implants are widely used: artificial heart valves, pacemakers, endoprostheses, metal structures, dental implants, etc. It is proved that in the presence of a foreign body the critical microbial number essential for the development of the infectious process is significantly reduced. On the surface of foreign bodies a number of microorganisms form biofilms (colonies of certain varieties of staphylococci), which sharply reduce the effectiveness of antibiotics. Indications for the removal of such foreign bodies involved in the current infectious process should be formulated taking into account both the positive side of the surgical intervention (elimination of the source of infection) and the negative ones - the trauma of a second operation (for example, to remove certain types of pacemakers requires an open heart surgery) and deficiency of the prosthetic function (sometimes, for example, with endocarditis of artificial valves, such manipulations are life-threatening).

The performed studies, based on the principles of evidence-based medicine, indicate that the algorithm for treating two forms of surgical infections can be considered proven.

It is proved that performing an operation with necrotizing fasciitis after 24 hours or more after diagnosis has resulted in a lethality reduction of up to 70%, and an operation up to 24 hours - a reduction in the lethality to 13%. A fundamentally important point is the need to stabilize hemodynamic indicators (not normalization!). It should be noted that surgical intervention to eliminate the necrosis zone refers to resuscitation measures, and the earlier the operation is performed, the greater the chances of the patient. Operative interventions conducted in the late period in the presence of a detailed picture of ICE and multi-organ failure, did not lead to a decrease in mortality.

It is also proved that an early operation with severe pancreatic necrosis does not lead to an improvement in the results of treatment. Indications for surgery are formulated by the end of the second week from the onset of the disease (the exception is the obstructive form of pancreonecrosis, the obstruction of the choledoch of any genesis in the region of the falcon nipple) in the absence of signs of infection of the gland. Two methods have become the standards in the diagnosis of the infectious process in the necrotic tissues of the pancreas. The first is a thin needle biopsy under the supervision of ultrasound or CT with subsequent Gram staining. The second method, which is becoming more widespread and has an evidentiary basis, is a dynamic evaluation of the level of procalcitonin. This semiquantitative method is quite simple and, probably, will take a worthy place in the practical work of surgical hospitals in the near future. Currently, he pretends to be the "gold standard" due to high specificity and sensitivity, low traumatism (1 ml of serum or plasma is sufficient) and high representativeness.

The main areas of treatment for sepsis and septic shock, which received an evidence base and reflected in the documents "Movement for effective treatment of sepsis," include:

• infusion treatment;
• use of vasopressors;
• inotropic treatment;
• use of small doses of steroids;
• use of recombinant activated protein C;
• transfusion treatment;
• ALV algorithm for acute lung injury / adult respiratory distress syndrome (SAD / ARDS);
• protocol of sedation and analgesia in patients with severe sepsis;
• the protocol of glycemic control;
• protocol of treatment of arthritis;
• protocol for the use of bicarbonate;
• prevention of deep vein thrombosis;
• prevention of stress ulcers;
• conclusion.

At the end of XX century. Three problems, representing for centuries an insoluble problem for clinicians, and first of all surgeons, negating many brilliant operations in various diseases, injuries and injuries - inflammation, infection and sepsis - were presented as a complete system. Modern ideas about the pathogenesis of inflammation allow us to state that this reaction is uniform for all types of damage and, moreover, is necessary for the restoration of the organism after a previous operation or trauma. This was clearly demonstrated by numerous experiments in which, in one way or another, the inflammatory response to an insignificant wound of the soft tissues in the experimental animal was disconnected. If in the control group all subjects were able to independently overcome the consequences of injury, then in the experimental group all the animals died.

In modern ideas about the infectious process, there is still no final clarity today. The entry of microorganisms into the wound channel leads to microbial contamination, but numerous works during the Great Patriotic War, various local conflicts, and the experience of peacetime surgeons prove that the microflora that pollutes the wound that colonizes it (vegetating in the wound) and causes the infectious process is three different concepts. Only ultrahigh doses of microorganisms, when their number exceeds 10 ⁶ per 1 g of tissue, entering the wound during experimental infection or, for example, in clinical practice with injuries of the left half of the large intestine, can immediately overcome the protective barriers of the macroorganism. Fortunately, such cases are rarely observed in practice. The need for differentiation of microbial contamination, microflora of the wound and microflora that causes the infectious process should be especially clearly understood when analyzing the data of the microbiological study of the wound detachment, as well as in analyzing the causes of the development of infectious complications.

With the modern approach to understanding the pathogenesis of sepsis, it is defined as a systemic inflammatory response to the infectious process. This interpretation causes in a number of cases an ambiguous reaction. In fact, each lesion is accompanied by inflammation at the local and systemic levels (signs of systemic inflammation).

Inflammation is an essential component of reparative regeneration, without which the healing process is impossible. However, according to all the canons of the modern treatment of sepsis, it must be considered as a pathological process that must be combated. This collision is well understood by all leading specialists in sepsis, so in 2001 an attempt was made to develop a new approach to the treatment of sepsis, which in essence continues and develops the theory of R. Bon. This approach was called the "PIRO concept" (PIRO - predisposition infection response outcome). The letter P denotes a predisposition (genetic factors preceding chronic diseases, etc.), AND - infection (the type of microorganisms, the localization of the process, etc.), P - result (outcome of the process) and O - response (the nature of the response of different systems organism for infection). This interpretation seems very promising, however, the complexity, heterogeneity of the process and the extreme breadth of clinical manifestations have not allowed to unify and formalize these features to date. Realizing all the limitations of the interpretation proposed by R. Bon, it is widely used based on two concepts.

Firstly, undoubtedly, severe sepsis is the result of the interaction of microorganisms and a macroorganism, which has resulted in a violation of the functions of one or several leading life support systems, which is recognized by all scientists involved in this problem.

Secondly, the simplicity and convenience of the approach used in the diagnosis of severe sepsis (the criteria of a systemic inflammatory reaction, the infectious process, the criteria for diagnosing organ disorders) make it possible to isolate more or less homogeneous groups of patients.

The use of such an approach has allowed to get rid of such ambiguously defined concepts as "septicemia", "septicopyemia", "chroniosepsis", "refractory septic shock".

The most important achievements in the practical implementation of the approach to the understanding of sepsis, proposed by R. Bon, was the acquisition of objective data on the epidemiology of sepsis, which showed for the first time that the frequency of severe sepsis exceeds the incidence of myocardial infarction, and the lethality in severe sepsis exceeds the mortality from myocardial infarction.

No less, and perhaps more important, the practical result of implementing this approach was the development of scientifically based methods of treating severe sepsis on the basis of the principles of clinical epidemiology and evidence-based medicine. The Barcelona Declaration, which objectively determined the treatment algorithms for patients with severe sepsis, largely helped to offset numerous speculations on the use of various methods for the treatment of sepsis. So, in particular, many of the proposed methods of immunocorrection, which are extremely widely used in Russian medical practice, have not been confirmed. The only method that received a theoretical justification for immunocorrection in sepsis is passive immuno-substitutive treatment. Conducted clinical trials revealed

• inconsistent data when using IgG, which does not allow us to recommend g
• its preparations for these purposes. The only one who received the evidence base
• method - the use of enriched immunoglobulins, containing IgG, IgM, IgA.

The use of extracorporal hemocorrection methods (hemodialysis or continued hemofiltration), widespread in Russia, has been shown only in the treatment of acute renal failure.

The Barcelona Declaration on the reduction of mortality in severe sepsis by 25% over 5 years as a result of the introduction of evidence-based treatment principles is encouraging. The efforts of specialists should be aimed at improving the effectiveness of treatment for this extremely severe category of patients. Today, this is possible if the efforts of scientists of different specialties are combined on the basis of the Conciliation Conference decisions and the theory of the pathogenesis of sepsis developed on their basis. However, there are still many unresolved issues related to early diagnosis and monitoring of sepsis, the possibility of its early and effective prediction.

As one of the important trends in the development of positive trends in the treatment of severe sepsis, we can name the immunophysiological approach, focused on the interaction of genetically determined mediators of an individual systemic inflammatory response.

This is not a mathematically verified balance of proinflammatory and compensatory anti-inflammatory cytokines, but of the interaction in a single process of mediators that perform a stimulating, inhibitory, ligand, adjuvant, and sometimes determinative action. Here, perhaps, it is appropriate to recall the judgment we received from the last century that life is "a symphony performed by the orchestra of instrument-mediators." Each instrument in the score has its own musical part, and together they create a synchronous polyphonic sound. Then a miracle is born, combining the creative beginning of the composer, the creative interpretation of the conductor and the creative individual perception of the listener. Systemic inflammatory reaction is given to the culminating part of the "symphony of life", its apotheosis. Perhaps such a simile comparison will facilitate understanding of the immunophysiology of individual systemic infectious inflammation, on the one hand, and the pathogenesis of sepsis, on the other.

[18], [19], [20], [21], [22], [23], [24],