Sepsis treatment protocol

Treatment of sepsis has been relevant throughout the entire period of study of this pathological condition. The number of methods used for its treatment is enormous. This can be partly explained by the heterogeneous nature of the septic process.

Crucial changes in treatment methods occurred after the adoption of agreed definitions of sepsis, severe sepsis and septic shock. This allowed different researchers to speak the same language, using the same concepts and terms. The second most important factor was the introduction of evidence-based medicine principles into clinical practice. These two circumstances made it possible to develop evidence-based recommendations for the treatment of sepsis, published in 2003 and called the Barcelona Declaration. It announced the creation of an international program known as the 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 global associations of specialists and distributed according to their level of evidence.

In accordance with the methodological recommendations, the following activities are proposed.

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Microbiological research

All samples for microbiological testing are taken immediately upon admission of the patient, before the start of antibacterial treatment. At least two blood samples must be taken for testing. One blood sample is taken by puncture of a peripheral vein, and the second - from a central venous catheter (if one was installed earlier). Samples of physiological fluids (urine, if a urinary catheter is installed or there are good reasons to exclude the possibility of a urinary tract infection), bronchial secretions, wound discharge and other samples in accordance with the clinical picture of the underlying pathology are also sent for microbiological testing.

Primary intensive care

Aimed at achieving the following parameter values in the first 6 hours of intensive treatment (activities are started immediately after diagnosis):

• CVP 8-12 mm Hg;
• mean blood pressure >65 mmHg;
• the amount of urine excreted is >0.5 ml/(kg h);
• mixed venous blood saturation >70%.

If transfusion of various infusion media fails to achieve an increase in central venous pressure and the level of mixed venous blood saturation to the indicated figures, then the following is recommended:

• transfusion of red blood cells until the hematocrit level reaches 30%;
• dobutamine infusion at a dose of 20 mcg/kg per minute.

Implementation of the specified set of measures allows us to reduce the mortality rate from 49.2 to 33.3%.

Antibacterial treatment

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

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

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Control of the source of infection

Every patient with signs of severe sepsis should be carefully examined to identify the source of the infectious process and implement appropriate source control measures, which include three groups of surgical interventions:

1. Abscess cavity drainage. An abscess is formed as a result of the inflammatory cascade and the formation of a fibrin capsule surrounding a fluid substrate consisting of necrotic tissue, polymorphonuclear leukocytes and microorganisms, and well known to clinicians as pus. Abscess drainage is a mandatory procedure in treatment, but the technique for its implementation is undergoing a certain evolution. The main trend in recent years has been drainage of an abscess using ultrasound equipment or CT, as well as endovideosurgical interventions. The use of modern navigation technology significantly reduces the risk of surgery due to reduced tissue trauma.
2. Secondary surgical treatment (necrectomy). Removal of necrotic tissues involved in the infectious process is one of the main tasks in achieving source control. Only by performing full surgical treatment can one achieve control over the local infectious process and, consequently, reduce the severity of the systemic reaction. Despite the fact that the manifestations of the consequences of the "cytokine storm" can be expressed to a significant degree, and sometimes determine an unfavorable outcome, surgery to remove necrotic infected tissues should be considered a priority task. The question of the extent of necrectomy in the absence of an infectious process in devitalized tissues remains unclear. Expanding the scope of surgical 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 has been proven that the presence of a foreign body significantly reduces the critical microbial number required for the development of the infectious process. On the surface of foreign bodies, a number of microorganisms form biofilms (colonies of some varieties of staphylococci), which sharply reduce the effectiveness of antibiotics. Indications for the removal of such foreign bodies involved in the current infectious process must be formulated taking into account both the positive side of the surgical intervention (elimination of the source of infection) and the negative - the trauma of repeated surgery (for example, open heart surgery is required to remove some types of pacemakers) and the deficiency of the prosthetic function (sometimes, for example, with endocarditis of artificial valves, such manipulations are life-threatening).

The conducted 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 has been proven that performing surgery for necrotizing fasciitis 24 hours or more after diagnosis reduces mortality to 70%, and performing surgery within 24 hours reduces mortality to 13%. A fundamentally important point is the need to stabilize hemodynamic parameters (not normalize!). It should be noted that surgical intervention to eliminate the necrosis zone refers to resuscitation measures, and the earlier the surgery is performed, the greater the patient's chances. Surgical interventions performed in the late period in the presence of a comprehensive picture of DIC and multiple organ failure did not lead to a decrease in mortality.

It has also been proven that early surgery for severe pancreatic necrosis does not improve treatment outcomes. Indications for surgery are formulated by the end of the second week from the onset of the disease (except for obstructive pancreatic necrosis, obstruction of the common bile duct of any genesis in the area of the Vater's papilla) in the absence of signs of gland infection. Two methods have become standards in diagnosing the infectious process in necrotic tissues of the pancreas. The first is a fine-needle biopsy under ultrasound or CT control with subsequent Gram staining. The second method, which is becoming more widespread and has an evidence base, is a dynamic assessment of the procalcitonin level. This semi-quantitative method is quite simple and is likely to take a worthy place in the practical work of surgical hospitals in the near future. At present, it claims to be the "gold standard" due to its high specificity and sensitivity, low trauma (1 ml of serum or plasma is sufficient) and high representativeness.

The main areas of treatment for sepsis and septic shock, which have received an evidence base and are reflected in the documents of the “Movement for Effective Sepsis Treatment”, include:

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

At the end of the 20th century, three problems that had been an insoluble task for clinicians, and especially surgeons, for centuries, which had brought to naught many brilliant operations for various diseases, wounds and injuries - inflammation, infection and sepsis - were presented as a holistic system. Modern ideas about the pathogenesis of inflammation allow us to assert that this reaction is the same for all types of damage and, moreover, is necessary for the restoration of the body after surgery or injury. This was clearly demonstrated by numerous experiments in which the inflammatory response to a minor wound of soft tissue in an experimental animal was switched off in one way or another. If in the control group all subjects were able to overcome the consequences of the wound on their own, then in the experimental group all animals died.

There is still no final clarity in modern concepts of the infectious process. The penetration of microorganisms into the wound channel leads to microbial contamination, but numerous studies during the Great Patriotic War, various local conflicts, and the experience of peacetime surgeons prove that the microflora contaminating the wound, colonizing it (vegetating in the wound) and causing the infectious process are three different concepts. Only ultra-high 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 wounds of the left half of the colon, are able to immediately overcome the protective barriers of the macroorganism. Fortunately, such cases are extremely rare in practice. The need to differentiate microbial contamination, wound microflora and microflora causing the infectious process should be especially clearly understood when analyzing the data of a microbiological study of wound discharge, as well as when analyzing the causes of the development of infectious complications.

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

Inflammation is a necessary component of reparative regeneration, without which the healing process is impossible. However, according to all the canons of the modern interpretation of sepsis, it must be considered as a pathological process that must be fought. This collision is well understood by all leading sepsis specialists, so in 2001 an attempt was made to develop a new approach to the treatment of sepsis, essentially continuing and developing the theories of R. Bon. This approach was called the "PIRO concept" (PIRO - predisposition infection response outcome). The letter P denotes predisposition (genetic factors, previous chronic diseases, etc.), I - infection (type of microorganisms, localization of the process, etc.), R - result (outcome of the process) and O - response (the nature of the response of various body systems to the infection). Such an interpretation seems very promising, but the complexity, heterogeneity of the process and the extreme breadth of clinical manifestations have not allowed to unify and formalize these signs to date. Understanding the limitations of the interpretation proposed by R. Bon, it is widely used based on two ideas.

Firstly, severe sepsis is undoubtedly the result of the interaction of microorganisms and the macroorganism, which has led to a disruption of the functions of one or more leading life support systems, which is recognized by all scientists studying this problem.

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

The use of this approach has made it possible to get rid of such ambiguously defined concepts as “septicemia”, “septicopyemia”, “chroniosepsis”, and “refractory septic shock”.

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

No less, and perhaps more important practical result of the implementation of this approach was the development of scientifically based methods of treating severe sepsis based on the principles of clinical epidemiology and evidence-based medicine. The Barcelona Declaration, which objectively defined algorithms for treating patients with severe sepsis, made it possible to largely neutralize numerous speculations on the use of various methods for treating sepsis. Thus, in particular, many of the proposed methods of immunocorrection, extremely widely used in domestic medical practice, have not been confirmed. The only method that has received theoretical justification for immunocorrection in sepsis is passive immunoreplacement therapy. The clinical trials revealed

• conflicting data when using IgG, which does not allow g to be recommended
• his preparations for these purposes. The only one that has received an evidence base
• method - use of enriched immunoglobulins containing IgG, IgM, IgA.

The use of methods of extracorporeal hemocorrection (hemodialysis or continuous hemofiltration) widely used in Russia is indicated only in the treatment of acute renal failure.

The Barcelona Declaration data on the reduction of mortality in severe sepsis by 25% over 5 years as a result of the implementation of treatment principles that have received an evidence base are encouraging. The efforts of specialists should be aimed at improving the effectiveness of treatment of this extremely severe category of patients. Today, this is possible provided that the efforts of scientists of various specialties are combined on the basis of the decisions of the Consensus Conference and the theory of sepsis pathogenesis developed on their basis. At the same time, there are still many unresolved issues related to early diagnosis and monitoring of sepsis, the possibility of its early and effective prediction.

One of the important directions for the development of positive trends in the treatment of severe sepsis is the immunophysiological approach, focused on the interaction of genetically determined mediators of the individual systemic inflammatory response.

We are not talking about a mathematically verified balance of pro-inflammatory and compensatory anti-inflammatory cytokines, but about the interaction in a single process of mediators that carry out stimulating, inhibiting, ligand, adjuvant, and sometimes determining effects. Here, perhaps, it is appropriate to recall the judgment inherited from the last century that life is a "symphony performed by an orchestra of mediator instruments." Each of the instruments in the score has its own musical part, and together they create a synchronous polyphonic sound. Then a miracle is born, combining the creativity of the composer, the creative interpretation of the conductor and the creative individual perception of the listener. The systemic inflammatory reaction is given the culmination of the "symphony of life", its apotheosis. Perhaps such a figurative comparison will facilitate the understanding of the immunophysiology of individual systemic infectious inflammation, on the one hand, and the pathogenesis of sepsis, on the other.

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