Effectiveness of empirical antibiotic treatment for severe sepsis. Algorithm for antimicrobial therapy for sepsis Modern treatment of sepsis

Treatment of septic patients should be carried out under constant clinical and laboratory control, including an assessment of the general condition, pulse, blood pressure and CVP, hourly urine output, body temperature, respiratory rate, ECG, pulse oximetry. It should be mandatory to study general blood and urine tests, indicators of acid-base state, electrolyte metabolism, blood residual nitrogen, urea, creatinine, sugar, coagulogram (clotting time, fibrinogen content, platelets, etc.). All these studies must be carried out at least once or twice a day in order to be able to make timely adjustments to the therapy.

Complex treatment of sepsis is one of the most difficult tasks. It usually consists of two main areas:

1. Active surgical treatment of primary and metastatic purulent foci.

2. General intensive treatment of a septic patient, the purpose of which is to quickly correct homeostasis.

Surgical treatment of sepsis

Surgical treatment is aimed at removal of septic focus and is carried out in any condition of the patient, often for health reasons. The operation should be extremely low-traumatic, as radical as possible, and preparation for it should be extremely short-term, using any light interval for intervention. The method of anesthesia is gentle. The best conditions for revision of the focus are provided with intubation anesthesia (induction - seduxen, ketamine; main anesthesia - NLA, GHB, etc.).

Surgical treatment of a purulent focus should be carried out with the obligatory observance of a number of requirements:

I. In case of multiple lesions, it is necessary to strive to perform the operation at the same time.

2. The operation is performed according to the type of surgical treatment of the piemic focus and consists in the complete excision of all non-viable tissues with an incision sufficient to open the existing pockets and leaks. The treated wound cavity is additionally treated with a pulsating stream of antibacterial liquid, laser beams, ultrasound, cryotherapy or evacuation.

3. Surgical treatment of a purulent focus is completed in various ways:

Suturing in conditions of active drainage of the wound with its washing and vecuum-aspiration or "flow" method;

Treatment of a wound under a bandage with multicomponent hydrophilic ointments or drainage sorbents;

Sewing up the wound tightly (for limited indications);

Suturing under conditions of transmembrane wound dialysis.

4. In all cases, after surgical treatment, it is necessary to create resting conditions in the wound area by immobilization to eliminate pain impulses, negative neuro-trophic influences, and tissue trauma.

When combining the seam of a purulent wound with active antibacterial drainage, washing the wound cavity with antiseptic solutions is carried out for 7-10 days daily for 6-12 hours, depending on the condition of the wound. The method of flow-aspiration drainage provides mechanical cleansing of the purulent focus from necrotic deutrite and has a direct antimicrobial effect on the wound microflora. Washing usually requires 1-2 liters of solution (0.1% dioxidine solution, 0.1% furagin solution, 3% boric acid solution, 0.02% furacilin solution, etc.). In the treatment of purulent processes caused by Clostridial microflora, solutions of hydrogen peroxide, potassium permanganate, metrogil are used for washing. The washing method is available, technically simple, and applicable in any conditions. It should be noted that lavage drainage for anaerobic infection is less effective than for purulent infection, since it does not lead to a rapid decrease in excess tissue edema.

Modern methods of active exposure to a purulent wound are aimed at a sharp reduction in the first and second phase of the early process. The main tasks of treating wounds in the first (purulent-necrotic) stage of the wound process are to suppress infection, eliminate hyperosmia, acidosis, activate the process of rejection of necrotic tissues, and adsorb toxic discharge from the wound. Thus, drugs for chemotherapy of a wound should have a simultaneous multidirectional effect on a purulent wound - antimicrobial, anti-inflammatory, necrolytic and analgesic.

Ointments on a hydrophilic (water-soluble) basis have now become the drugs of choice in the treatment of purulent wounds; Any hypertonic solutions have an extremely short-term effect on a purulent wound (no more than 2-8 hours), since they are quickly diluted with wound secretions and lose their osmotic activity. In addition, these solutions (antiseptics, antibiotics) have a certain damaging effect on the tissues and cells of the macroorganism.

Multi-component ointments have been developed (levosin, levomikol, levonorsin, sulfamilon, dioxycol, sulfamekol), which include antimicrobial agents (chloramphenicol, norsulfazole, sulfadimethoxin, dioxidin), an activator of tissue metabolic processes (methyluracil), a local anesthetic ointment (polyethylene oxide), provides its dehydrating effect in a purulent wound. Due to hydrogen bonds, polyethylene oxide (PEO) forms complex compounds with water, and the bond of water with the polymer is not rigid: taking water from tissues, PEO relatively easily gives it to a gauze bandage. The ointment reduces interstitial hypertension, is able to suppress the wound microflora after 3-5 days. The ointment lasts 16-18 hours, the dressing is usually changed daily.

In recent years, water-absorbing draining sorbents such as "Sorbilex", "Debrisan" (Sweden), "Galevin" (RF), carbon adsorbents of granular and fibrous structure have found wide application for influencing the focus of purulent infection. Local application of draining sorbents has an effective anti-inflammatory effect, accelerates wound healing processes and shortens treatment times. Dressings are made daily, the sorbents on the dressing are removed with hydrogen peroxide and a stream of antiseptic. Partial regional detoxification (adsorption of toxic substances by sorbents) is also achieved by the sorbent.

Wound dialysis- a method of osmoactive transmembrane wound drainage developed in our academy, combining continuous dehydration effects with controlled chemotherapy in a purulent-septic focus (E.A. Selezov, 1991). This is a new original highly effective method of draining wounds and purulent-septic foci. The method is provided by a dialysis membrane drain, in the cavity of which an osmoactive polymer gel is exchanged as a dialysis solution. Such drainage ensures the dehydration of edematous inflammatory tissues and the elimination of stagnation of wound exudate, has the ability to transmembrane absorption of toxic substances (vasoactive mediators, toxic metabolites and polypeptides) from the wound, and creates conditions for regional detoxification. At the same time, the introduction of antibacterial drugs into the dialysate ensures their intake and uniform diffusion from the drainage into the tissue of the pyemic focus to suppress the pathogenic microflora. The method has simultaneously antimicrobial, anti-inflammatory, anti-ischemic, detoxifying effect and creates optimal conditions for regenerative processes in the wound focus.

Membrane dialysis drain functions like a miniature artificial kidney, and wound dialysis is in essence a method of intracorporeal regional detoxification, which prevents intoxication associated with a septic focus. A real opportunity has appeared to change the usual path of resorption of toxic substances from the pyemic focus into the general blood flow in the opposite direction - from the tissues of the septic focus into the cavity of the dialyzing membrane drainage.

With abscesses of the liver, kidneys, spleen, lungs, revealed using the latest examination methods (computed tomography, ultrasound diagnostics), they resort to active surgical tactics, up to the removal of the focus. Early drainage of abscesses and retroperitoneal phlegmons also reduces mortality in sepsis.

Significantly shortens the time and improves the results of treatment in managed abacterial environment and oxybarotherapy, normalizing the oxygen balance of the body and having an inhibitory effect on anaerobes.

Intensive care for sepsis and septic shock

Based on the literature data and our own experience, the following can be recognized as the main areas of intensive care for sepsis and septic shock:

1) Early diagnosis and sanitation of the septic focus;

3) Inhibition of the body's hyperergic reaction to aggression;

4) Correction of hemodynamics taking into account the stage of septic shock;

5) Early respiratory support, as well as diagnosis and treatment of RDS;

6) Intestinal decontamination;

7) Fight against endotoxicosis and prevention of PON;

8) Correction of blood clotting disorders;

9) Suppression of the activity of mediators;

10) Immunotherapy;

11) Hormone therapy;

12) Nutritional Support

13) General care of a septic patient;

14) Symptomatic therapy.

Antibacterial therapy. When using antibacterial agents, it is assumed that pathogenic bacteria are the cause of this case, but the possibility of another infectious agent associated with fungi and viruses should not be overlooked. In most hospitals, cases of sepsis associated with Gr- and Gr + bacteria, which are part of the normal microflora of the body, are recorded.

Microbiological diagnostics sepsis is crucial in the selection of effective antibiotic therapy regimens. Subject to the requirements for the correct sampling of material, positive hemiculture in sepsis is detected in 80-90% of cases. Modern methods of blood culture research make it possible to record the growth of microorganisms within 6-8 hours, and after another 24-48 hours, to obtain an accurate identification of the pathogen.

For an adequate microbiological diagnosis of sepsis, the following rules should be observed.

1 ... Blood for research must be taken before starting antibiotic therapy. In cases where the patient has already received antibiotics and they cannot be canceled, blood is taken immediately before the next administration of the drug (at the minimum concentration of the antibiotic in the blood).

2 ... Blood for research is taken from a peripheral vein. Blood sampling from a catheter is not allowed, unless a catheter-associated sepsis is suspected.

3 ... The required minimum of sampling is two samples taken from the veins of different arms with an interval of 30 minutes.

4 ... It is more optimal to use standard commercial vials with ready-made culture media, rather than vials closed with cotton-gauze stoppers prepared in the laboratory.

5 ... Blood sampling from a peripheral vein should be carried out with careful observance of asepsis.

Early antibiotic treatment begins before isolation and identification of the culture, which is extremely important for its effectiveness. More than 20 years ago it was shown (B. Kreger et al, 1980) that adequate antibiotic therapy for sepsis at the first stage reduces the risk of death by 50%. Recent studies (Carlos M. Luna, 2000), published at the 10th European Congress on Clinical Microbiology and Infectious Diseases, confirmed the validity of this position in ventilator-associated pneumonia. This circumstance is of particular importance in immunocompromised patients, where a delay in treatment of more than 24 hours can quickly result in an unfavorable outcome. Immediate empiric parenteral broad-spectrum antibiotics are recommended whenever infection and sepsis are suspected.

The initial choice of starting imperial adequate therapy is one of the most significant factors determining the clinical outcome of the disease. Any delay in initiating adequate antibiotic therapy increases the risk of complications and death. This is especially true for severe sepsis. It has been shown that the results of treatment with antibacterial drugs for severe sepsis with multiple organ failure (MOF) are significantly worse than for sepsis without MOF. In this regard, the use of the maximum regimen of antibiotic therapy in patients with severe sepsis should be carried out at the earliest stage of treatment (J. Cohen, W. Lynn. Sepsis, 1998; 2: 101)

In the early phase of treatment choice of antibiotic based on known variants of bacterial sensitivity and situational assumption of infection (empirical therapy schemes). As mentioned above, strains of microorganisms in sepsis are often associated with nosocomial infection.

The correct choice of antimicrobial agents is usually determined by the following factors: a) probable pathogen and its sensitivity to antibiotics , b) the underlying disease and the patient's immune status, v) pharmacokinetics of antibiotics , G) the severity of the disease, e) assessment of the cost / effectiveness ratio.

In most hospitals the use of broad-spectrum antibiotics and antibiotic combinations is considered the rule, which ensures their high activity against a wide range of microorganisms before the results of microbiological research become known (Table 1). The guaranteed broad spectrum of suppression of infection is the main reason for such antibiotic therapy. Another argument in favor of using a combination of different types of antibiotics is a decrease in the likelihood of developing antibiotic resistance during treatment and the presence of synergy, which makes it possible to achieve rapid suppression of the flora. The simultaneous use of several antibiotics in patients with the threat of sepsis is justified by many clinical results. When choosing an adequate treatment regimen, one should take into account not only the coverage of all potential pathogens, but also the possibility of participation in the septic process of multi-resistant hospital strains of microorganisms.

Table 1

Empiric therapy for sepsis

Characteristics of sepsis	Sepsis without PON	Severe sepsis with PON
With an unidentified primary focus In surgical departments In the department of R&IT With neutropenia	Cefotaxime 2 g 3-4 times a day (ceftriaxone 2 g once a day) +/- aminoglycoside (gentamicin, tobramycin, netilmicin, amikacin) Ticarcillin / clavulanate 3.2 g 3-4 times a day + aminoglycoside Ceftazidime 2 g 3 times a day +/- amikacin 1 g per day Cefepime 2 g 2 times a day +/- amikacin 1 g per day Ciprofloxacin 0.4 g 2-3 times a day +/- amikacin 1 g per day Ceftazidime 2 g 3 times a day +/- amikacin 1 g per day +/- vancomycin 1 g 2 times a day Cefepime 2 g 2 times a day +/- amikacin 1 g a day +/- vancomycin 1 g 2 times a day	Amikacin 1 g per day Imipenem 0.5 g 3 times a day Imipenem 0.5-1 g 3 times a day Meropenem 0.5-1 g 3 times a day Imipenem 1 g 3 times a day +/- vancomycin 1 g 3 times a day * Meropenem 1 g 3 times a day +/- vancomycin 1 g 2 times a day *
With an established primary focus Abdominal After splenectomy Urosepsis Angiogenic (catheter)	Lincomycin 0.6 g 3 times a day + aminiglycoside 3rd-generation cephalosporin (cefotaxime, cefoperazone, ceftazidime, ceftriaxone) + lincomycin (or metronidazole) Ticarcillin / clavulanate 3.2 g 3-4 times a day + aminoglycoside Cefuroxime 1.5 g 3 times a day Cefotaxime 2 g 3 times a day Ceftriaxone 2 g once a day Fluoroquinolone +/- aminoglycoside Cefepime 2 g 2 times a day Vancomycin 1 g 2 times a day Rifampicin 0.3 g 2 times a day	Imipenem 0.5 g 3 times a day Meropenem 0.5 g 3 times a day Cefepime 2 g 2 times a day + metronidazole 0.5 g 3 times a day +/- aminoglycoside Ciprofloxacin 0.42 g 2 times a day + metronidazole 0.5 g 3 times a day Cefepime 2 g 2 times a day Imipenem 0.5 g 3 times a day Meropenem 0.5 g 3 times a day Imipenem 0.5 3 times a day Meropenem 0.5 g 3 times a day Vancomycin 1 g 2 times a day +/- gentamicin Rifampicin 0.45 g 2 times a day + ciprofloxacin 0.4 g 2 times a day

*) Note. Vancomycin is added at the second stage of therapy (after 48-72 hours) if the starting regimen is ineffective; with subsequent ineffectiveness at the third stage, an antifungal drug (amphotericin B or fluconazole) is added.

Combinations of 3rd generation cephalosporins (ceftriaxone) with aminoglycosides (gentamicin or amikacin) are often used. Other cephalosporins such as cefotaxime and ceftazidime are also widely used. They all have good efficacy against many microorganisms in sepsis in the absence of neutropenia. Ceftriaxone has a long half-life, so it can be used once a day. Antibiotics that have a short half-life should be used on a high daily dose regimen. In neutropenic patients, penicillins (mezlocillin) with increased activity against Pseudomonas aeruginosa in combination with aminoglycosides, when administered several times a day, are an effective agent against nosocomial infections. Used successfully to treat sepsis imipenem and carbapenem.

Determining the optimal antibiotic regimen in patients with sepsis requires studies in large patient populations. Vancomycin is often used when Gy + infection is suspected. When determining the sensitivity of antibiotics, therapy can be changed.

Modern works focus on a single use of aminoglycosides once a day in order to reduce their toxicity, for example, ceftriaxone in combination with methylmycin or amikacin and ceftriaxone once a day. Single daily doses of aminoglycosides in combination with long-acting cephalosporins have a sufficient effect and are safe in the treatment of severe bacterial infection.

There are a number of reasons for choosing monotherapy. Its cost, as well as the frequency of adverse reactions, is less. An alternative to combination therapy can be monotherapy with drugs such as carbapenem, imipenem, cilastatin, fluoroquinolones... It is well tolerated and highly effective. At present, it can be recognized that the most optimal mode of empirical therapy for severe sepsis with PON is carbopenems (imipenem, meropenem) as drugs with the widest spectrum of activity, to which the least level of resistance of nosocomial strains of gram-negative bacteria is noted. In some cases, cefepime and ciprofloxacin are adequate alternatives to carbopenems. In the case of catheter sepsis, the etiology of which is dominated by staphylococci, reliable results can be obtained from the use of glycopeptides (vancomycin). Drugs of a new class of oxazolidinones (linezolid) are not inferior to vancomecin in activity against Gr + microorganisms and have similar clinical efficacy.

In cases where it was possible to identify microflora, the choice of antimicrobial drug becomes direct(Table 2). It is possible to use monotherapy with antibiotics with a narrow spectrum of action, which increases the percentage of successful treatment.

table 2

Etiotropic therapy for sepsis

Microorganisms	1st row means	Alternative remedies
Gram-positive Staphylococcus aureus MS	Oxacillin 2 g 6 times a day Cefazolin 2 g 3 times a day	Lincomycin 0.6 g 3 times a day Amoxicillin / clavulanate 1.2 g 3 times a day
Staphylococcus aureus MR Staphylococcus epidermidis	Vancomycin 1 g 2 times a day	Rifampicin 0.3-0.45 g 2 times a day + co-trimoxazole 0.96 g 2 times a day (ciprofloxacin 0.4 g 2 times a day)
Staphylococcus viridans	Benzylpenicillin 3 million units 6 times a day	Ampicillin 2 g 4 times a day Cefotaxime 2 g 3 times a day Ceftriaxone 2 g once a day
Streptococcus pneumoniae	Cefotaxime 2 g 3 times a day Ceftriaxone 2 g once a day	Cefepime 2 g 2 times a day Imipenem 0.5 g 3 times a day
Enterococcus faecalis	Ampicillin 2 g 4 times a day + gentamicin 0.24 g per day	Vancomycin 1 g 2 times a day +/- gentamicin 0.24 g per day Linezolid 0.6 g 2 times a day
Gram-negative E.coli, P.mirabilis, H.influenzae	Cefotaxime 2 g 3 times a day Ceftriaxone 2 g once a day	Fluoroquinolone
	Imipenem 0.5 g 3 times a day Meropenem 0.5 g 3 times a day	Ciprofloxacin 0.4 g 2 times a day Cefepime 2 g 2 times a day
Enterobacter spp., Citrobacter spp.	Imipenem 0.5 g 3 times a day	Ciprofloxacin 0.4 g 2 times a day
P.vulgaris, Serratia spp.	Meropenem 0.5 g 3 times a day Cefepime 2 g 2 times a day	Amikacin 1 g per day
Acinetobacter spp.	Imipenem 0.5 g 3 times a day Meropenem 0.5 g 3 times a day	Cefepime 2 g 2 times a day Ciprofloxacin 0.4 g 2 times a day
	Ceftazidime 2 g 3 times a day + amikacin 1 g per day Ciprofloxacin 0.4 g 2-3 times a day + amikacin 1 g per day	Imipnem 1 g 3 times a day + amikacin 1 g per day Meropinem 1 g 3 times a day + amikacin 1 g per day Cefepime 2 g 3 times a day + amikacin 1 g day
	Amphotericin B 0.6-1 mg / kg per day	Fluconazole 0.4 g once a day

In most patients, it is advisable to use subclavian vein(especially with septic pneumonia). With a lesion focus on the lower extremities, in the kidneys, good results are obtained long-term arterial infusion antibiotics.

The drugs should be prescribed in courses of 2-3 weeks at medium and maximum doses, using simultaneously 2-3 drugs administered by different routes (orally, intravenously, intraarterially). The patient should not be given the same antibiotic that has already been used in the last two weeks. To maintain the required concentration of the drug in the body, it is usually administered several times a day (4-8 times). If the lungs are affected, it is advisable to administer antibiotics intratracheally through a bronchoscope or catheter.

Prescribing antibiotics for septic shock preference should be given to bactericidal drugs. In conditions of a sharp weakening of the body's defenses, bacteriostatic agents (tetracycline, chloramphenicol, oleandomycin, etc.) will not be effective.

Worked well in the treatment of sepsis sulfa drugs. It is advisable to use the sodium salt of etazole (1-2 g 2 times a day in the form of a 10% solution intramuscularly or in the form of a 3% solution of 300 ml in a vein drip). However, their side and toxic effects are also known. In this regard, in the presence of modern highly effective antibiotics, sulfa drugs are gradually losing their importance. In the treatment of sepsis, drugs are used nitrofuran series- furodonin, furozolidone, and antiseptic dioxidin 1.0-2.0 g / day. Metronidazole possesses a wide spectrum of action against spore- and non-spore-forming anaerobes, as well as protozoa. However, one should take into account its hepatotoxicity. Prescribe it intravenously drip of 0.5 g every 6-8 hours.

When carrying out long-term antibiotic therapy, it is necessary to take it into account. negative effects- activation of the kinin system, impaired blood clotting (due to the formation of antibodies to coagulation factors) and immunosuppression (due to inhibition of phagocytosis), the occurrence of superinfection. Therefore, the therapy should include antikinin drugs (contrikal, trasilol 10-20 thousand units intravenously 2-3 times a day).

For prevention of superinfection(candidiasis , enterocolitis) must be applied antimycotic agents (nystatin, levorin, diflucan), eubiotics(mexase, mexaform). Destruction of normal intestinal microflora under the influence of antibiotics can lead to vitamin deficiency. intestinal bacteria are producers of vitamins of the "B" group and partly of the "K" group. Therefore, simultaneously with antibiotics, they must be prescribed vitamins.

With antibiotic therapy, it is necessary to remember about such a possible complication as exacerbation reaction, which is associated with increased breakdown of microbial bodies and the release of microbial endotoxins. Clinically, it is characterized by excitement, sometimes delirium, fever. Therefore, antibiotic treatment should not be started with so-called shock doses. Of great importance for the prevention of these reactions is the combination of antibiotics with sulfonamides, which adsorb microbial toxins well. In severe cases of endotoxemia, it is necessary to resort to extracorporeal (outside the patient's body) detoxification.

Detoxification (detoxification) therapy

The progressive development of surgical infection from a clinical point of view is, first of all, the growing intoxication of the body, which is based on the development of severe microbial toxemia.

Under endogenous intoxication it means the receipt from the focus and accumulation in the body of various toxic substances, the nature and nature of which is determined by the process. These are intermediate and final products of normal metabolism, but in increased concentrations (lactate, pyruvate, urea, creatinine, bilirubin), products of unlimited proteolysis, hydrolysis of glycoproteins, lipoproteins, phospholipids, enzymes of the coagulation, fibrinolytic, kallikriinkinin inflammation system, antibodies, mediators amines, waste products and decay of normal, opportunistic and pathogenic microflora.

From the pathological focus, these substances enter the blood, lymph, interstitial fluid and spread their influence to all organs and tissues of the body. Endotoxicosis is especially difficult with septic multiple organ failure. in the stage of decompensation of the internal detoxification mechanisms of the body's defense. Dysfunction of the liver is associated with the failure of the natural mechanisms of internal detoxification, renal failure implies the failure of the excretory system, etc.

There is no doubt that the primary measure in the treatment of endotoxicosis should be the sanitation of the source and the prevention of toxins from the primary affect. Intoxication decreases already as a result of opening and draining a purulent focus, due to the removal of pus along with microbial toxins, enzymes, tissue breakdown products, biologically active chemical compounds.

However, practice shows that for severe eudotoxicosis, elimination of the etiological factor does not solve the problem, since autocatalytic processes, including more and more vicious circles, contribute to the progression of endogenous intoxication even with a completely eliminated primary source. At the same time, traditional (routine) methods of treatment are not able to break the pathogenetic links of severe endotoxicosis. The most pathogenetically substantiated in such a situation are methods of influence aimed at elimination of toxins from the body, which should be used against the background of a full range of traditional therapy aimed at correcting all detected disorders.

A comprehensive approach to the treatment of severe forms of surgical infection includes conservative and active surgical detoxification methods. Endotoxemia grade is determined, including the clinical picture, by monitoring changes in metabolism - the content of blood electrolytes, residual nitrogen, urea, creatinine, bilirubin and its fractions, enzymes. Toxemia is usually characterized by: hyperazotemia, hypercreatinemia, bilirubinemia, hyperkalemia, hyperenzymemia, acidemia, renal failure.

Comprehensive detoxification methods for sepsis

In the early period of toxemia, with preserved diuresis, conservative methods of detoxification are used, including hemodilution, correction of acid base balance, water-electrolyte metabolism, forced diuresis.

Hemodilution carried out by infusion of 10% albumin solution 3 ml / kg, protein 5-6 ml / kg , rheopolyglucin or neohemodesis 6-8 ml / kg, as well as solutions of crystalloids and glucose 5-10-20% - 10-15 ml / kg with the inclusion of antiplatelet agents that simultaneously improve microcirculation by reducing peripheral vascular resistance (heparin, curantil, trental). Hemodilution should be considered safe to a hematocrit of 27-28%.

It should be noted that a decrease in the concentration and excretory function of the kidneys limits the possibilities of conservative detoxification methods, because with inadequate diuresis, overhydration may occur. Hemodilution is usually carried out in the oliguric stage.

Against the background of hemodilution, to enhance the effectiveness of detoxification of the patient's blood, forced diuresis. Stimulation of diuresis is carried out using a water load using 10-20% glucose solutions, alkalizing blood by introducing 200-300 ml of a 4% sodium bicarbonate solution and lasix up to 200-300 mg per day. With preserved diuresis, manitol 1 g / kg, 2.4% solution of eufilin up to 20 ml, dalargin up to 2-4 ml are used. In order to reduce blood clotting, increase hepatic blood flow and prevent platelet aggregation, patients are prescribed papaverine, trental, instenon, courantil, no-shpu, nicotinic acid; for the prevention and elimination of capillary permeability disorders - ascorbic acid, diphenhydramine.

During the day, patients are usually injected with 2000-2500 ml of various solutions. The number of solutions administered intravenously and enterally is strictly controlled taking into account diuresis, fluid loss during vomiting, diarrhea, perspiration and indicators of hydration (auscultation and radiography of the lungs, hematocrit, CVP, BCC).

Enterosorption

Based on an oral dosage of sorbent 1 tablespoon 3-4 times a day. The most active means of enterosorption include enterodesis, enterosorb, and various brands of coal. Their use with preserved bowel function provides an artificial enhancement of the processes of elimination of low and medium molecular weight substances from the circulating blood, which helps to neutralize and reduce the absorption of toxins from the gastrointestinal tract. The greatest detoxification effect is achieved with the combined use of enterodesis and intravenous neohemodesis.

Of great importance for reducing toxicosis is the strengthening of the destruction of toxins in the body, which is achieved by the activation of oxidative processes (oxygen therapy, hyperbaric oxygenation). Local hypothermia significantly weakens the resorption of toxins from the pyemic focus.

Hyperbaric oxygenation

An effective method of combating local and general hypoxia in endotoxicosis is the use of hyperbaric oxygenation (HBO), which improves microcirculation in organs and tissues, as well as central and organ hemodynamics. The therapeutic effect of HBO is based on a significant increase in the oxygen capacity of body fluids, which makes it possible to quickly increase the oxygen content in cells that suffer from hypoxia as a result of severe endotoxicosis. HBO increases the indices of humoral factors of nonspecific defense, stimulates an increase in the number of T- and B-lymphocytes, while the content of immunoglobulins significantly increases.

TO surgical detoxification methods should include all modern dialysis-filtration, sorption and plasmapheresis methods of extracorporeal hemocorrection in endotoxicosis. All these methods are based on the removal of toxins and metabolites of various masses and properties directly from the blood, and allow to reduce endogenous intoxication. Surgical detoxification techniques include:

1. Hemodialysis, ultrahemofiltration, hemodiafiltration.
2. Hemisorption, lymphosorption; immunosorption.
3. Therapeutic plasmapheresis.
4. Xenosplenoperfusion.
5. Xenohepatoperfusion.
6. Flowing ultraviolet irradiation of autologous blood.
7. Extracorporeal hemooxygenation.
8. Laser irradiation of autologous blood.
9. Peritoneal dialysis.

The main indication for the use of surgical methods of detoxification is to determine the degree of toxicity of blood, lymph and urine with a high content of substances with an average molecular weight (over 0.800 conventional units), as well as the level of urea up to 27.6 nmol / l, creatinine up to 232.4 nmol / l, a sharp increase in the content of blood enzymes (ALT, AST, lactate dehydrogenase, cholinesterase, alkaline phosphatase, aldolase), metabolic or mixed acidosis, oligoanuria or anuria.

When planning extracorporeal hemocorrection for endotoxicosis, it is necessary to take into account that different methods of extracorporeal detoxification have different directions of action. This is the basis for their combined use, when the capabilities of one of them are insufficient to obtain a quick therapeutic effect. Hemodialysis removes electrolytes and low molecular weight substances. Ultrafiltration methods also remove fluid and medium molecular weight toxins. The non-dialyzability of toxic substances through semipermeable membranes is the basis for the use of sorption methods of detoxification, which are aimed at removing mainly medium- and high-molecular substances. With high toxicity of blood plasma, the most reasonable is the combination of hemodiafiltration and sorption methods with therapeutic plasmapheresis.

Hemodialysis (HD)

Hemodialysis is performed using an artificial kidney apparatus. Dialysis is a process in which substances in solution are separated due to unequal diffusion rates through a membrane, since membranes have different permeabilities for substances with different molecular weights (semipermeability of membranes, dialyzability of substances).

In any case, the "artificial kidney" includes the following elements: a semipermeable membrane, on one side of which the patient's blood flows, and on the other side, a saline dialysis solution. The heart of the "artificial kidney" is a "dialyzer, in which a semipermeable membrane plays the role of a" molecular sieve "that separates substances depending on their molecular size. The membranes used for dialysis have practically the same pore size 5-10 nm and therefore only small molecules not associated with protein. To prevent blood clotting in the apparatus, anticoagulants are used. In this case, due to transmembrane diffusion processes, the concentration of low molecular weight compounds (ions, urea, creatinine, glucose and other substances with a small molecular weight) in the blood is equalized and dialysate, which provides extrarenal cleansing of the blood.With an increase in the pore diameter of the semipermeable membrane, movement of substances with a higher molecular weight occurs.With the help of hemodialysis, it is possible to eliminate hyperkalemia, azotemia and acidosis.

The operation of hemodialysis is very complex, requires expensive and complex equipment, a sufficient number of trained medical personnel and the presence of special "renal centers".

It should be borne in mind that in practice, in endotoxicosis, the situation often develops in such a way that toxins and cellular degradation products mainly bind to proteins, forming a strong chemical complex that is difficult to remove. Hemodialysis alone in such cases, as a rule, cannot solve all the problems.

Ultrafiltration (UV)

This is the process of separation and fractionation of solutions, in which macromolecules are separated from the solution and low molecular weight compounds by filtration through membranes. Blood filtration, performed as an emergency measure for pulmonary and cerebral edema, allows you to quickly remove up to 2000-2500 ml of fluid from the body. With UV, fluid is removed from the blood by creating a positive hydrostatic pressure in the dialyzer by partially clamping the venous line or by creating negative pressure on the outer surface of the membrane in the dialyzer. The filtration process under increased hydrostatic pressure of the blood mimics the natural process of glomerular filtration, since the renal glomeruli function as an elementary ultrafilter of blood.

Hemofiltration (HF)

It is carried out against the background of intravenous administration of various solutions for 3-5 hours. In a short period of time (up to 60 minutes), it is possible to carry out active dehydration of the body through the excretion pathways of up to 2500 ml of ultrafiltrate. The resulting ultrafiltrate is replaced by Ringer's solution, glucose and plasma-substituting solutions.

Indications for GF are uremic intoxication, unstable hemodynamics, severe overhydration. For health reasons (collapse, anuria), GF is sometimes carried out continuously for 48 hours or more with a fluid deficit of up to 1-2 liters. In the process of continuous long-term GF, the activity of blood flow through the hemofilter is from 50 to 100 ml / min. The rate of blood filtration and displacement ranges from 500 to 2000 ml per hour.

UF and GF methods are most often used as resuscitation measures in patients with endotoxic shock in a state of severe overhydration.

Hemodiafiltration / HDF /

With enhanced detoxification, dehydration and correction of homeostasis, hemodiafiltration is used, which combines both hemodialysis and hemofiltration. Dilution of blood with isotonic glucose-saline solution, followed by ultrafiltration reconcentration to the same volume, makes it possible to reduce the concentration of plasma impurities, regardless of molecular size. The clearance for urea, creatinine, medium molecules is the highest with this method of detoxification. The clinical effect consists in the most pronounced detoxification and dehydration of the body, correction of the water-electrolyte composition of the blood, acid base balance, normalization of gas exchange, the system of regulation of the aggregate state of the blood, indicators of central and peripheral hemodynamics and the central nervous system.

"Dry dialysis"

In this case, hemodialysis usually begins with increasing the transmembrane pressure in the dialyzer without circulating dialysate fluid. After the required amount of fluid has been removed from the patient, the transmembrane pressure is reduced to a minimum and the dialysate supply is turned on. In the remaining time, thus, the metabolites are excreted from the body without removing water. Isolated ultrafiltration can also be performed at the end of dialysis or in the middle of the procedure, but the former is most effective. With this method of conducting hemodialysis, it is usually possible to fully dehydrate the patient, lower blood pressure and avoid collapse or hypertensive crisis at the end of dialysis.

"Artificial placenta"

This is a method of hemodialysis in which blood from one patient flows to one side of the membrane, while another patient sends his blood to the same membrane, only from the opposite side. Any low molecular weight toxins or metabolites can be transferred between subjects, one of which is a patient, without crossing the elements of the immuno-chemical system of each patient. In this way, a patient with acute reversible failure can be supported during the critical period by dialysis blood from a healthy donor with well-functioning natural mechanisms of internal detoxification (for example, a healthy mother can support her child).

Hemosorption

Hemoperfusion through activated charcoal (hemocarboperfusion) is an effective method of detoxification of the body, imitating the antitoxic function of the liver.

Blood perfusion is usually carried out using a roller-type pump through a column (devices UAG-01, AGUP-1M, etc.) filled with a sterile sorbent. For this, uncoated activated carbons of the IGI, ADB brands are used; BAU, AR-3, GSU, SKN, SKN-1K, SKN-2K, SKN-4M; sorbents with synthetic coating SUTS, SKN-90, SKT-6, FAS, fibrous sorbent "Aktilen" and others.

Hemosorbents have a high absorption capacity for a wide range of toxic products. They absorb and selectively remove bilirubin, residual nitrogen, uric acid, ammonia, bile acids, phenols, creatinine, potassium and ammonium from the body. Coating the carbon sorbents with materials compatible with blood significantly reduces the trauma of the formed elements and reduces the sorption of blood proteins.

The column with the sorbent is connected to the patient's circulatory system using an arterio-venous shunt. For external bypass surgery, the radial artery and the most developed branch of the lateral and medial saphenous veins in the lower third of the forearm are usually used.

Heparinization is carried out at the rate of 500 IU of heparin per 1 kg of patient weight with neutralization of residual heparin with protamine sulfate.

One hemosorption session usually lasts from 45 minutes to two hours. The rate of hemoperfusion through a column with a sorbent (volume 250 ml) is 80-100 ml / min, the volume of perfused blood is 1-2 BCC (10-12 liters) for 30-40 minutes. The interval between hemosorption sessions is 7 days or more.

Bile acids, phonols, amino acids, and enzymes are also sorbed. The potassium level during 45 minutes of hemocarboperfusion decreases from 8 to 5 meq / l, which significantly reduces the risk of the toxic effect of hyperkalemia on the heart and prevents intraventricular blockade, cardiac arrest in the diastole phase.

It should be borne in mind that hemosorption is accompanied by trauma to the blood cells - the number of erythrocytes, leukocytes and especially platelets decreases. Other complications of hemosorption are also possible. For critically ill patients, this is a risky procedure.

Lymphosorption

The thoracic lymphatic duct is drained (lymphatic drainage). Lymph is collected in a sterile vial and returned to the bloodstream by gravity, passing through a column with a sorbent (volume of "SKN" coal 400 ml), or a roller perfusion pump of the "UAG-01" apparatus is used. The use of the device allows in a short time to perform 2-3-fold perfusion of lymph through a sorbent along a closed circulation circuit and thereby increase the detoxification effect of lymphosorption. Usually 2-3 sessions of lymphosorption are performed.

Immunosorption

Immunosorption refers to extracorporeal methods of immunocorrection and detoxification.

We are talking about sorbents of a new generation, the development of which has just begun, but their capabilities are extremely wide. With this type of hemosorption, blood is purified from pathological proteins in an extracorporeal circuit containing an immunosorbent (selective sorption). Activated carbon, porous silicas, glass and other granular macroporous polymers are used as carriers for binding biologically active substances.

Immunosorbents are antigen (AG) or antibody (AB) fixed on an insoluble matrix as an affinity ligand. Upon contact with blood, AG fixed on sorbents binds the corresponding AT in it; in the case of AT fixation, the binding of complementary AGs occurs. The specificity of the interaction between AG and AT is extremely high and is realized at the level of the correspondence of the active fragments of the AG molecule to a certain part of the AT macromolecule, which is included in it like a key in a lock. A specific AG-AT complex is formed.

Modern technology makes it possible to obtain antibodies against practically any compound that must be extracted from biological media. At the same time, low molecular weight substances that do not possess antigenic properties are no exception.

Antibody immunosorbents are used for the selective extraction of microbial toxins from the blood. The extremely high cost of immunosorbents is likely to limit the practical application of immunosorption.

Therapeutic plasmapheresis (PF)

The term "apheresis" (Greek) means - removal, taking away, taking. Plasmapheresis ensures the separation of plasma from the corpuscles without injuring the latter and is currently the most promising method of detoxification in the treatment of critical conditions. The method allows you to remove pathogens and toxins from the blood, which are protein macromolecules, as well as other toxic compounds dissolved in blood plasma. Plasmapheresis allows only blood plasma to be detoxified (sorption, UFO, ILBI, sedimentation), returning the formed blood cells to the patient.

Most commonly used discrete (fractional) centrifugal plasmapheresis. At the same time, blood is exfused from the subclavian vein into a polymer container "Gemakon-500" with a preservative. The taken blood is centrifuged at 2000 rpm in a K-70 or TsL-4000 centrifuge for 10 minutes. Plasma is removed from the container. Erythrocytes are washed twice in 0.9% sodium chloride solution in a centrifuge for 5 minutes at 2000 rpm. The washed erythrocytes return to the patient's bloodstream. Plasma substitution is carried out by hemodez, rheopolyglucin, native donor single-group plasma and other infusion media.

During the procedure, up to 1200-2000 ml of plasma is removed in 2-2.5 hours, i.e. 0.7-1.0 bcc. The volume of the replaced plasma must be greater than that of the removed. Fresh frozen plasma is able to quickly restore BCC and oncotic pressure. It is a supplier of various blood coagulation factors, immunoglobulins, and is recognized as the most valuable physiological product. Usually, the patient undergoes 3-4 PF operations with an interval of every other day, with replacement not with saline, but with freshly frozen donor plasma.

The clinical effect of PP consists in a detoxification effect - toxic metabolites, medium and large molecular toxins, microbial bodies, creatinine, urea and others are eliminated from the body (excreted, extracted).

Plasmapheresis using blood separators

Plasmapheresis is carried out on the "Amnico" apparatus (USA) or other similar apparatus for 2-3 hours. Blood is taken from the subclavian vein. The optimal blood withdrawal rate is 50-70 ml / min. Centrifugation speed 800-900 rpm. In one procedure, 500-2000 ml of plasma is removed. The isolated plasma is replaced with 10-20% albumin solution in the amount of 100-400 ml, 400 ml rheopolyglucin solution, 0.9% sodium chloride 400-1200 solution. With good contouring of the peripheral veins, the cubital vein is punctured and blood is returned to it.

Saccular plasmapheresis

It is produced using containers "Gemakon-500/300". Withdrawal of blood is carried out from the cubital vein into a plastic container with a volume of 530-560 ml. Blood centrifugation is carried out at 2000 rpm for 30 minutes. Then the plasma is removed, and 50 ml of isotonic sodium chloride solution with 5000 U of heparin is added to the cell suspension and the patient is injected with a jet. During the procedure, 900-1500 ml of plasma is removed from the patient, which is replaced fractionally at the time of centrifugation of the blood with 10-20% albumin solution in the amount of 100-300 ml, 400 ml rheopolyglucin solution , 0.9% sodium chloride solution 400-1200 ml.

Saccular cryoplasmapheresis

Plasma is collected in sterile 300 ml bags. 50 ml of isotonic sodium chloride solution is added to the remaining cell suspension and injected into the patient in a stream.

The separated plasma is stored at a temperature of 4C for 24 hours, and then the cryoproteins (cryogel) formed in it in the presence of heparin and with a decrease in temperature are precipitated at 3000 rpm for 20 minutes also at a temperature of 4C. Plasma is taken into sterile vials and frozen at -18C until the next procedure, when it will be returned to the patient without cryoproteins and other pathological products (fibronectin, cryoprecipitins, fibrinogen, immune complexes, etc.). In one procedure, 900-1500 ml of plasma is removed, which is replaced with frozen plasma of the patient, harvested in the previous procedure.

Cryoplasma sorption

Cryoplasmapheresis procedure, in which the isolated plasma, cooled to 4 ° C, is passed through 2-3 columns with hemosorbent with a volume of 150-200 ml each, and then heated to 3 ° C and returned to the patient. Cryoproteins and other activated carbon sorbed material are removed. In total, 2000-3500 ml of plasma is passed through the hemosorbent during the procedure.

The disadvantages of plasmapheresis are well known. Together with plasma, immunoglobulins, hormones and other biologically active compounds necessary for the body are given. This should be taken into account in patients diagnosed with sepsis. But usually 2-4 sessions of plasmapheresis lead to a steady improvement in the patient's condition.

Membrane plasmapheresis

Requires careful selection of the dialysis membrane of the hemofilter, namely the pore size. All toxic compounds have different molecular weights and require a sufficient pore size in the membrane for their elimination. Membranes for plasmapheresis have pores from 0.2 to 0.65 μm , which ensures the passage of water, electrolytes and all plasma proteins and at the same time prevents the passage of cellular elements. The use of membranes with pores of 0.07 microns allows the body to preserve albumins and immunoglobulins during plasmapheresis.

Xenosplenoperfusion

Refers to extracorporeal methods of immunocorrection and detoxification. In the scientific literature, the method has various names - extracorporeal donor / porcine / spleen connection (ECPDS), biosorption, xenosorption, splenosorption ,. hemosorption on the spleen, detoxification therapy by the xenosepleen and others.

This is a priority method for the treatment of acute and chronic sepsis using a short-term extracorporeal connection of the xenospleen to the patient's blood vessels. Usually, in case of sepsis, complex detoxification (after hemosorption sessions with membrane oxygenation, ultraviolet irradiation of autologous blood, ILBI, plasmapheresis) for the correction of severe immunodeficiency on 4-6 days include EKPDS.

The spleen of the pig has found application as a powerful organ of immunological protection. Sterile, washed from the blood of the animal with a physiological solution, it not only actively absorbs microbes and toxins, but also throws biologically active substances into the patient's blood to be purified that stimulate the mechanisms of immune defense.

The patient's blood is pumped by a perfusion pump through the vessels of the xenospleen for 40 minutes through a veno-venous shunt (subclavian vein - ulnar vein). The rate of hemoperfusion through a biological filter is usually 30-40 ml / min. A good effect of using xenospleen is provided only in combination with conventional intensive therapy.

Extracorporeal perfusion of xenospleen slices

To avoid some complications during hemoperfusion through the organ (extravasates, blood loss, etc.), they resort to this method of immunocorrection and detoxification. The spleen is taken at a meat-packing plant from healthy outbred pigs. In the operating room, under sterile conditions, sections with a thickness of 2-4 mm are made, followed by washing from the blood in 1.5-2 liters of saline at a temperature of 18-20C. The sections are placed in a bottle with two droppers for recirculating washing in 400 ml of saline with the addition of 2000 U of heparin. Then the perfusion system is connected to the patient's vessels. The shunt is usually veno-venous. The blood flow rate through the biosorbent is 80-100 ml / min for 0.5-1 hours.

Xenohepatoperfusion

The method is indicated for acute liver failure to maintain disturbed liver function and detoxify the body.

An extracorporeal perfusion system is used using isolated live hepatocytes in an auxiliary liver device (AVP). Isolated viable hepatocytes are obtained by the enzymatic-mechanical method from the liver of healthy pigs with a body weight of 18-20 kg in an amount of up to 400 ml of dense suspension.

The AVP is connected to the catheterized subclavian veins. The PF-0.5 rotor separates whole blood into plasma and cellular fraction. Plasma enters the oxygenator-heat exchanger, where it is saturated with oxygen and warmed up to 37C; then the plasma contacts the hepatocytes. After contact with isolated hepatocytes, the plasma combines with the cellular fraction of the blood and returns to the patient's body. The rate of perfusion through the AVP for blood is 30-40 ml / min, for plasma 15-20 ml / min. Perfume time from 5 to 7.5 hours.

Hepatocytes in extracorporeal artificial perfusion support systems perform all hepatic functions, they are functionally active towards well-known metabolites: ammonia, urea, glucose, bilirubin, "hepatic toxin".

Flowing ultraviolet irradiation of autologous blood

An effective transfusion operation (autotransfusion of photomodified blood - AUFOK) is used to reduce endotoxicosis and stimulate the body's protective forces.

With the help of "Isolde", FMK-1, FMR-10 apparatuses. ВМР-120 for 5 minutes at a blood flow rate of 100-150 ml / min irradiate the patient's blood with UV light in a thin layer and sterile conditions. Blood is irradiated in a volume of 1-2 ml / kg. Usually, the course of treatment includes 3-5 sessions, depending on the severity of the patient's condition and the severity of the therapeutic effect. In the conditions of FMK-1, one session is sufficient.

Reinfusion of photomodified blood is a powerful factor affecting the body and its immune homeostasis. The effect of irradiated with UV light autologous blood on the body is being intensively studied. The existing experience has shown that UV autologous blood stimulates an increase in the number of lymphocytes, activates redox processes, immune cellular and humoral defense reactions; has a bactericidal, detoxifying and anti-inflammatory effect. It is the positive effect on the indicators of cellular immunity that predetermines the inclusion of the autologous blood ultraviolet irradiation method in the complex treatment of sepsis.

Extracorporeal membrane oxygenation (ECMO)

This is an assisted oxygenation method based on partial replacement of natural lung function. It is used as a method of intensive treatment of acute respiratory failure (ARF), with hypercapnia under conditions of intensive mechanical ventilation, and with multiple organ failure.

Various stationary membrane oxygenators ("membrane lung") are used, which are connected to the arterial line of the heart-lung machine for long-term auxiliary oxygenation.

The principle of the membrane oxygenator (MO) device is based on the diffusion of oxygen through a gas-permeable membrane into the patient's blood. The blood is perfused through thin-walled membrane tubes, which are fixed in plastic cylinders, which are purged with oxygen according to the counterflow principle.

Indications for the beginning of ECMO are a decrease in RaO 2 indicators below 50 mm Hg. Art. in patients with ARF of polyetiological genesis, and as a resuscitation measure in the treatment of terminal respiratory and circulatory disorders in hypoxic coma (PaO 2 below 33 mm Hg). In all patients, as a result of ECMO, it is possible to significantly increase PaO 2.

Low-flow membrane oxygenation of blood (MO)

Currently, in addition to the treatment of ARF, the field of application of blood oxygenation with small volumes is being formed and in other very diverse situations. Short-term perfusion with low blood volume MO can be used:

1.as an independent method for improving the rheological characteristics of blood, activating phagocytosis, detoxification, immunocorrection, nonspecific stimulation of the body;

2. in combination with other perfusion methods - improvement of oxygen transport during hemosorption, oxygenation of erythrocytes and improvement of their rheological properties during plasmapheresis, oxygenation of plasma, lymph and hepatocytes in the "auxiliary liver" apparatus; oxygenation of blood and plasma by connecting isolated donor organs, for example, xenospleen, activation of ultraviolet irradiation of blood, etc .;

3. regional IMO - lung perfusion in ARF, liver perfusion in acute liver failure (ARF).

In the clinic, MMO is successfully used to combat endotoxicosis. It is known that hypoxia impairs hepatic circulation and reduces the detoxifying function of the liver. With blood pressure not exceeding 80 mm Hg. Art., necrosis of hepatocytes occurs after 3 hours. In this situation, extracorporeal oxygenation of the liver portal system is very promising.

For oxygenation of blood in this case, a capillary hemodialyzer of an artificial kidney is used. Oxygen gas is introduced into the column instead of dialysis fluid. The perfusion system with a dialyzer is connected to the patient's vessels according to the scheme: superior vena cava - portal vein. The volumetric blood flow rate in the system is maintained within the range of 100-200 ml / min. The pO 2 level at the outlet of the oxygenator is on average 300 mm Hg, Art. The method allows you to maintain and restore the disturbed liver function.

Intravascular laser irradiation of autologous blood (ILBI)

For the purpose of non-specific immunostimulation, laser irradiation of the patient's blood is carried out (HNL - helium-neon laser). For ILBI, a physiotherapeutic laser device ULF-01 is used, which has an active element GL-109 and an optical attachment with a thin monofilament light guide inserted into the subclavian catheter or through an injection needle after venipuncture. The duration of the first and last sessions is 30 minutes, the rest - 45 minutes (usually 5-10 sessions per course of treatment).

ILBI promotes the activation of the immune response, gives a pronounced analgesic, anti-inflammatory and hypocoagulant effect, increases the phagocytic activity of leukocytes.

Thus, the existing methods of extracorporeal hemocorrection are able to temporarily replace the functions of the most important body systems - respiratory (oxygenation), excretory (dialysis, filtration), detoxification (sorption, apheresis, xenohepatoperfusion), immunocompetent (xenosplenoperfusion). mononuclear macrophage (immunosorption).

Considering the multicomponent nature of severe endotoxicosis, with generalized severe sepsis and, especially, with septic shock, only the combined use of existing detoxification methods can be the most pathogenetically justified.

It must be remembered that dialysis, sorption, plasmapheresis methods of extracorporeal detoxification affect only one of the components of endotoxicosis - toxemia, and with the centralization of blood circulation limited to correction of circulating, but not deposited and sequestered blood... The latter problem is partially solved by performing before detoxification hemocorrection pharmacological decentralization of blood circulation or sequential use of ILBI, UFO autologous blood and methods of extracorporeal detoxification (see the lecture "Thermal trauma", in volume 1 of this monograph).

Peritoneal dialysis (PD)

This is a method of accelerated detoxification of the body. The presence of natural semi-permeable membranes in the body, such as the peritoneum, pleura, pericardium, bladder, basement membrane of the glomeruli of the kidneys, and even the uterus, made it possible for a long time to raise the question of the possibility and expediency of their use for extrarenal cleansing of the body. Various methods of cleansing the body by washing the stomach and intestines are also based on the principle of dialysis and are well known.

Of course, many of the methods listed above (pleurodialysis, uterine dialysis, etc.) are only of historical interest, but the use of peritoneal dialysis, the so-called peritoneal dialysis, is successfully developing at the present time, sometimes competing in a number of parameters with hemodialysis or exceeding last.

However, this method is also not devoid of significant drawbacks (first of all, the possibility of developing peritonitis). Peritoneal dialysis is cheaper than hemodialysis and many other detoxification methods. The exchange through the peritoneum is also more effective in the sense of removing a wider range of metabolites from the patient's body than is the case with other methods of extrarenal cleansing. The peritoneum is able to remove harmful toxic substances (products of protein-free nitrogen, urea, potassium, phosphorus, etc.) from the body into the dialysis fluid injected into the abdominal cavity. Peritoneal dipalysis also makes it possible to introduce the necessary salt solutions and medicinal substances into the body.

In recent years, peritoneal dialysis has been widely used in surgical practice in the treatment of diffuse purulent peritonitis, i.e. local dialysis directly in the septic focus. The method of directed abdominal dialysis makes it possible to correct violations of water-salt metabolism, to dramatically reduce intoxication by removing toxins from the abdominal cavity, washing out bacteria, removing bacterial enzymes, and removing exudate.

There are two types of PD:

I / continuous (flow) PD, performed through 2-4 rubber tubes inserted into the abdominal cavity. Sterile dialysis fluid is continuously perfused through the abdominal cavity at a flow rate of 1–2 L / h;

2 / fractional (intermittent) PD - introduction of a portion of dialysis fluid into the abdominal cavity with a change in it after 45-60 minutes.

As a dialysis solution, isotonic saline solutions, balanced in blood plasma, with antibiotics and novocaine are used. To prevent fibrin deposition, 1000 U of heparin is added. The possibility of overhydration with overload of the heart and pulmonary edema due to the absorption of water into the blood is dangerous. We need strict control over the amount of injected and removed fluid.

The dialysate includes sodium bicarbonate or sodium acetate, characterized by buffering properties, and allowing to maintain the pH within the required range throughout the dialysis, ensuring the regulation of acid-base balance. Adding 20-50 g of glucose with insulin to the solution makes it possible to carry out dehydration. It is possible to withdraw up to 1-1.5 liters of resorbed liquid. However, this removes only 12-15% of toxic substances.

The use of albumin in the dialysate significantly increases the efficiency of PD. The process of nonspecific sorption of toxic substances on the protein macromolecule is switched on, which allows maintaining a significant concentration gradient between the plasma and the dialysis solution until the adsorbent surface is completely saturated ("protein dialysis").

Of great importance for the successful conduct of PD is the metosmolarity of the dialysis fluid. The osmotic pressure of the extracellular fluid and blood plasma is 290-310 mosm / l, so the osmotic pressure of the dialysate should be at least 370-410 mosm / l. The temperature of the dialysate should be 37 -38C. Each liter of solution is injected with 5000 U of heparin, to prevent infection, up to 10 million U of penicillin or other antibacterial agents are injected into the solution.

The use of extracorporeal detoxification methods is shown against the background of hemodynamic stabilization. In the early stages of septic shock, it is possible to carry out hemosorption or prolonged low-flow hemofiltration; in the future, it is possible to use plasmapheresis in combination with other methods of physiotherapy (ILBI).

The main goal in the treatment of SIRS is control of the inflammatory response... Almost 100 years ago, doctors discovered that it was possible to weaken the body's response to certain foreign substances by reintroducing them. Based on this, injections of killed bacteria were used as vaccines with various types of fever. Apparently, this technique can be used for prophylaxis in patients at risk of developing SIRS. For example, there are recommendations to use injections of monophosphoryl lipid-A (MPL), a derivative of Gr-endotoxin, as one of the methods of prevention. When using this technique in an experiment in animals, a decrease in hemodynamic effects in response to the introduction of endotoxin was noted.

At one time it was suggested that the use of corticosteroids should be beneficial in sepsis, as they are able to reduce the inflammatory response in cases of SIRS, which may improve outcome. However, these hopes did not materialize. In careful clinical testing in two large centers, the beneficial effects of steroids in septic shock were not found. This issue is highly controversial. We can say that with our current state of providing drugs, we simply do not have other drugs to stabilize and reduce membrane permeability. Antagonists of TNF, monoclonal antibodies, antagonists to IL-1 receptors, etc. are being tested and put into practice. However, control over the activity of mediators is probably a matter of the future. There is still much to be learned and put into practice here.

Taking into account the hyperergic reaction of the sympatho-adrenal system and the adrenal glands, the violation of the cytokine balance of the body with a powerful release of a large number of mediators in response to aggression, and, as a consequence, the imbalance of all links of homeostasis, it is necessary to use methods that allow blocking or compensating for the above processes. One such method is antistress therapy (AST).

It is fundamentally important to start the use of AST in septic patients as early as possible, before the development of cytokine cascade reactions and refractory hypotension, then these extreme manifestations of the body's reaction to aggression may be prevented. The AST method developed by us involves the combined use of an A 2 -adrenoreceptor agonist clonidine, neuropeptide dalargin and calcium antagonist isoptine... The use of AST is advisable in patients whose condition severity is more than 11 points according to ARASNA II, as well as with concomitant ulcerative lesions of the gastrointestinal tract, hyperacid gastritis, repeated sanitation of the abdominal cavity (it does not replace antibacterial, immunocorrective, detoxification and other therapy; however, against its background, they efficiency increases).

It should be started as early as possible: with intramuscular premedication, if the patient enters the operating room, or with the beginning of intensive care in the ward. The patient is sequentially injected with A 2 -adrenomimetic clonidine - 150 - 300 mcg / day, or ganglion blocker pentamine - 100 mg / day, the neurotransmitter dalargin - 4 mg / day, calcium antagonist - isoptin (nimotop, dilzem) - 15 mg / day ...

An integral component of the intensive care of sepsis is circulatory supportive therapy, especially with the development of septic shock syndrome. The pathogenesis of arterial hypotension in septic shock continues to be studied. First of all, it is associated with the development of the phenomenon of mosaic tissue perfusion and accumulation in various organs and tissues, either vasoconstrictors(thromboxane A2, leukotrienes, catecholamines, angiotensin II , endothelin), or vasodilators(NO-relaxing factor, cytokinins, prostaglandins, platelet activating factor, fibronectins, lysosomal enzymes, serotonin, histamine).

Early stages of development septic shock(hyperdynamic stage), the effects of vasodilators prevail in the vessels of the skin and skeletal muscles, which is manifested by high cardiac output, reduced vascular resistance, hypotension with warm skin. However, already in this situation, vasoconstriction of the hepatic-renal and splenic zones begins to develop. The hypodynamic stage of septic shock is associated with the prevalence of vasoconstriction in all vascular zones, which leads to a sharp increase in vascular resistance, a decrease in cardiac output, a total decrease in tissue perfusion, persistent hypotension and MOF.

Attempts to correct circulatory disorders must be made as early as possible under strict control for the parameters of central, peripheral hemodynamics and volemia.

The first remedy in this situation is usually volume replenishment... If pressure continues to be low after volume replenishment, dopamine or dobutamine. If hypotension persists, correction can be made adrenaline. A decrease in the sensitivity of adrenergic receptors occurs in various forms of shock, therefore, optimal doses of sympathomimetics should be used. As a result of stimulation of alpha- and beta-adrenergic and dopaminergic receptors, there is an increase in cardiac output (beta-adrenergic effect), an increase in vascular resistance (alpha-adrenergic effect) and blood flow to the kidneys (dopaminergic effect). The adrenergic vasopressor effect of adrenaline may be required in patients with persistent hypotension while using dopamine or in those who respond only to high doses. With refractory hypotension, it is possible to use NO-factor antagonists. Methylene blue (3-4 mg / kg) has this effect.

It should be noted that the above treatment regimen for septic shock is not always effective. In this case, you need to carefully evaluate the objective indicators of hemodynamics and volemia (cardiac output, SV, CVP, PSS, BCC, blood pressure, heart rate), accurately navigate the existing hemodynamic disorders (cardiac, vascular failure, hypo- or hypervolemia, combined disorders) and correct intensive therapy in a particular patient in a specific time period (inotropic drugs, vasoplegics, vasopressors, infusion media, etc.). Always consider reperfusion syndrome arising in the process of treating a septic patient and it is imperative to use inhibitors of biologically active substances (BAS) and methods of neutralizing or removing endotoxins (sodium bicarbonate, proteolysis inhibitors, extracorporeal detoxification methods, etc.).

In many cases, additional cautious the use of small doses of gangliolytics. So, usually fractional (2.2-5 mg) or drip pentamine in a dose of 25-30 mg in the first hour significantly improves peripheral and central hemodynamics, eliminates hypotension. These positive effects of additional therapy with gangliolytics are associated with an increase in the sensitivity of adrenergic receptors to endogenous and exogenous catecholamines and adrenergic agonists, an improvement in microcirculation, the inclusion of previously deposited blood into active blood flow, a decrease in cardiac output resistance, an increase in cardiac SV and BCC. In this case, one should take into account the possibility of increasing the concentration of biologically active substances, toxins and metabolic products in the blood as the microcirculation normalizes, especially if its disturbances were long-term. Due to this, in parallel, it is necessary to carry out active therapy for reperfusion syndrome. Careful adherence to these rules over the past 20 years allows us to more successfully cope with septic shock at different stages of its development. Similar results in patients with obstetric-gynecological sepsis were obtained by Dr. N.I. Terekhov.

Infusion-transfusion therapy for sepsis

Infusion therapy is aimed at correcting metabolic and circulatory disorders, restoring normal homeostasis indicators. It is carried out in all patients with sepsis, taking into account the severity of intoxication, the degree of volemic disorders, violations of protein, electrolyte and other types of metabolism, the state of the immune system.

The main tasks infusion therapy are:

1 ... Detoxification of the body by the method of forced diuresis and hemodilution. For this purpose, 3000-4000 ml of polyionic Ringer's solution and 5% glucose are injected intravenously at the rate of 50-70 ml / kg per day. Daily urine output is maintained within 3-4 liters. In this case, control over CVP, blood pressure, diuresis is necessary.

2 ... Maintaining the electrolyte and acid-base state of the blood. With sepsis, hypokalemia is usually noted due to the loss of potassium through the wound surface and with urine (daily potassium loss reaches 60-80 mmol). The acid-base state can change, both towards alkalosis and acidosis. Correction is carried out according to the generally accepted method (1% potassium chloride solution for alkalosis or 4% sodium bicarbonate solution for acidosis).

3 ... Maintaining circulating blood volume (BCC).

4 ... Correction of hypoproteinemia and anemia. Due to the increased consumption of bulk and intoxication, the protein content in patients with sepsis is often reduced to 30-40 g / l, the number of erythrocytes is up to 2.0-2.5 x 10 12 / l, with an HB level below 40-50 g / l ... A daily transfusion of complete protein preparations (native and dry plasma, albumin, protein, amino acids), fresh heparinized blood, erythromass, washed erythrocytes is required.

5 ... Improvement of peripheral blood circulation, rheological parameters of blood and prevention of platelet aggregation in capillaries. For this purpose, it is advisable to infuse intravenous rheopolyglucin, hemodez, prescribe heparin 2500-5000 IU 4-6 times a day; orally administer as a disaggregant - acetylsalicylic acid (1-2 g per day) together with vicalin or quamatel under the control of a coagulogram, the number of platelets and their aggregation ability.

Intensive infusion therapy should be carried out for a long time until stable stabilization of all indicators of homeostasis. Therapy requires catheterization of the subclavian vein. It is convenient, since it allows not only to administer drugs, but also to take blood samples repeatedly, measure CVP, and monitor the adequacy of treatment.

An approximate scheme of infusion-transfusion therapy in patients with sepsis (volume of ITT - 3.5-5 l / day):

I. Colloidal solutions:

1) polyglucin 400.0

2) hemodez 200.0 x 2 times a day

3) rheopolyglucin 400.0

B. Crystalloid solutions:

4) glucose 5% - 500.0 "

5) glucose 10-20% -500.0 x 2 times a day with insulin, KC1-1.5 g, NaC1- 1.0 g

6) Ringer's solution 500.0

7) Reambirin 400.0

II. Protein preparations:

8) solutions of amino acids (alvezin, aminone, etc.) - 500.0

9) protein 250.0

10) fresh citrated blood, erythro-suspension - 250-500.0 every other day

III. Solutions that correct acid base balance and electrolyte balance disorders:

11) KC1 solution 1% - 300.0-450.0

12) sodium bicarbonate 4% solution (calculation by base deficit).

1U. If necessary, preparations for parenteral nutrition (1500-2000 calories), fat emulsions (intralipid, lipofundin, etc.) in combination with amino acid solutions (aminone, aminosol), as well as intravenous administration of concentrated glucose solutions (20-50%) with insulin and solution of 1% potassium chloride.

At anemia it is necessary to carry out regular transfusions of freshly preserved blood, erythro-suspension. The use of dextrans against the background of oliguria should be limited due to the risk of developing osmotic nephrosis. Large doses of dextrans increase hemorrhagic disorders.

Usage respiratory support may be required in patients with SIRS or MOF. Respiratory support relieves stress on the oxygen delivery system and lowers the oxygen price of respiration. Gas exchange is improved due to better oxygenation of the blood.

Enteral nutrition should be prescribed as early as possible (still additional recovery of peristalsis), in small portions (from 25-30 ml) or drip-pouring balanced humanized infant formula, or a mixture of Spasokukotsky or special balanced nutritional mixtures ("Nutrizon", "Nutridrink", etc.). If it is impossible to swallow, inject the mixture through a nasogastric tube, incl. through NITK. This can be justified by: a) food, being a physiological stimulus, triggers peristalsis; b) full parenteral compensation is impossible in principle; c) by starting peristalsis, we reduce the chance of intestinal bacterial translocation.

Oral administration or tube administration should be carried out after 2-3 hours. With an increase in the discharge through the probe or the appearance of an eructation, a feeling of bursting -1-2, skip the injection; in the absence - increase the volume up to 50 - 100 ml. It is better to inject nutrient mixtures through a tube drip, which makes it possible to increase the effectiveness of nutritional support and to avoid these complications.

Balance and total calorie intake should be checked daily; from the 3rd day after the operation, it should be at least 2500 kcal. Deficiency in composition and calorie should be compensated for by intravenous administration of glucose solutions, albumin, fat emulsions. Perhaps the introduction of 33% alcohol, if there are no contraindications - cerebral edema, intracranial hypertension, severe metabolic acidosis. Correct the "mineral" composition of the serum, introduce a full set of vitamins (regardless of oral nutrition " With "not less than 1 g / day. And the whole group" B "). In the presence of a formed intestinal fistula, it is desirable to collect and return the discharge through a nasogastric tube or into the discharge intestine.

Contraindications to oral or tube feeding are: acute pancreatitis, nasogastric tube discharge> 500 ml, NITC discharge> 1000 ml.

Immunity correction methods

An important place in the treatment of patients with sepsis is occupied by passive and active immunization. Both non-specific and specific immunotherapy should be used.

In acute sepsis, passive immunization is indicated. Specific immunotherapy should include the administration of immune globulins (gamma globulin 4 doses 6 times every other day), hyperimmune plasma (antistaphylococcal, antipseudomonal, anticolibacillary), whole blood or its fractions (plasma, serum, or leukocyte suspension) from 100 immunized donors -200ml).

A decrease in the number of T-lymphocytes responsible for cellular immunity indicates the need to replenish the leukocyte mass or fresh blood from an immunized donor or reconvalescent. A decrease in B-lymphocytes indicates a lack of humoral immunity. In this case, it is advisable to transfuse immunoglobulin or immune plasma.

Carrying out active specific immunization (toxoid) in the acute period of sepsis should be considered unpromising, since it takes a long time (20-30 days) to produce antibodies. In addition, it should be borne in mind that the septic process develops against the background of an extremely tense or already depleted immunity.

In chronic sepsis or during the recovery period in acute sepsis, the appointment of active immunization agents - toxoids, autovaccines is indicated. Toxoid is injected at 0.5-1.0 ml with an interval of three days.

To increase immunity and increase the body's adaptive abilities, immunocorrectors and immunostimulants are used: polyoxidonium, thymazine, thymalin, T-activin, immunofan in I ml 1 time for 2-5 days (increase the content of T- and B-lymphocytes, improve the functional activity of lymphocytes) , lysozyme, prodigiosan, pentoxil, levamisole and other drugs.

In sepsis, a differentiated approach to the correction of immune deficiency is required, depending on the severity of immunity disorders and SIRS. Immunotherapy is necessary for patients in whom the need for intensive therapy has arisen against the background of a chronic inflammatory process, with a history of a tendency to various inflammatory diseases (chronic immunodeficiency is likely) and with severe SIRS.

Regardless of the severity of the condition, nonspecific biogenic stimulants are shown: metacil, mildronate or mummy. Extracorporeal immunopharmacotherapy with immunophan normalizes the ratio of cells of the main classes of subpopulations of T-lymphocytes, activates the early stages of antitelogenesis and promotes the maturation and differentiation of immunocompetent cells. The use of recombinant IL-2 (roncoleukin) is promising.

Considering that one of the starting points in the development of secondary immunodeficiency is a hyperergic stress reaction, the use of stress-protective therapy makes it possible to correct immunity at an earlier date. The combined use of stress-protective, adaptive therapy and efferent methods of detoxification is as follows. After the admission of patients to the intensive care unit with the start of infusion therapy, neuropeptide dalargin 30 μg / kg / day or instenon 2 ml / day is injected intravenously.

When positive numbers of CVP are reached, in order to reduce the hyperergic stress reaction, stabilize hemodynamics and correct metabolism, clonidine is included in the intensive care at a dose of 1.5 μg / kg (0.36 μg / kg / hour) intravenously drip once a day, in parallel continuing infusion therapy. After patients recover from septic shock, pentamine is injected intramuscularly at a dose of 1.5 mg / kg / day, 4 times a day during the catabolic stage of sepsis to continue neurovegetative protection. Bioprotector mildronate is prescribed intravenously from 1 to 14 days at a dose of 7 mg / kg / day 1 time per day; Actovegin - intravenous drip once a day at 15-20 mg / kg / day.

ILBI sessions(0.71-0.633 microns, power at the output of the light guide 2 mW, exposure 30 minutes) is carried out from the first day (6 hours after the start of ITT), 5-7 sessions within 10 days. Plasmapheresis is started in patients with severe sepsis after hemodynamic stabilization; in other cases, in the presence of grade II-III endotoxicosis.

The procedure for programmed plasmapheresis is carried out as follows. 4 hours before PF, pentamine 5% - 0.5 ml is injected intramuscularly. The ILBI session (according to the method described above) is carried out in 30 minutes. before plasmapheresis (PF). Preloading is carried out by infusion of rheopolyglucin (5-6 ml / kg) with trental (1.5 mg / kg). After preloading, 5 mg pentamine is administered intravenously every 3-5 minutes in a total dose of 25-30 mg. Blood sampling is carried out in vials with sodium citrate at the rate of 1/5 of the BCC, after which the infusion of 5% glucose solution (5-7 ml / kg) with protease inhibitors (counterkal 150-300 U / kg) is started. During glucose infusion, intravenously administered: CaCl 2 solution - 15 mg / kg, diphenhydramine - 0.15 mg / kg, pyridoxine hydrochloride solution (vitamin B 6) - 1.5 mg / kg.

After blood sampling, sodium hypochlorite is injected into the vials at a concentration of 600 mg / l, the sodium hypochlorite / blood ratio is 1.0-0.5 ml / 10 ml. The blood is centrifuged for 15 minutes. at a speed of 2000 rpm. Subsequently, the plasma is exfused into a sterile vial, and the erythrocytes, after dilution with a 1: 1 Disol solution, are returned to the patient.

Instead of the removed plasma, donor plasma (70% of the volume) and albumin (protein) - 30% of the volume are injected in the same amount.

Sodium hypochlorite is injected into the exfused plasma at a concentration of 600 mg / l, the sodium hypochlorite / blood ratio is 2.0-1.0 ml / 10 ml (193). After that, the plasma is cooled to +4, +6 0 С in a household refrigerator with an exposure time of 2-16 hours. The plasma is then centrifuged for 15 minutes. at a speed of 2000 rpm. The precipitated cryogel is removed, the plasma is frozen in a freezer at a temperature of -14 ° C. A day later, the patient is given the next PF session: the exfused plasma is replaced with thawed autoplasma. The number of PF sessions is determined by clinical and laboratory indicators of toxemia and ranges from 1 to 5. In the presence of positive blood cultures, it is better not to return the exfused plasma to the patient.

In order to correct secondary immunodeficiency, prevent bacterial and septic complications, high efficiency shows method of extracorporeal processing of leukocytes immunophan... The method of extracorporeal processing of leukocytes with immunofan is as follows.

Donated blood is taken through the central venous collector in the morning in the amount of 200-400 ml. As an anticoagulant, heparin is used at the rate of 25 U / ml of blood. After collection, vials with exfused and heparinized blood are centrifuged for 15 minutes at a speed of 1500 rpm, after which the plasma is exfused. A buffy coat is collected in a sterile vial and diluted with a solution of NaCl 0.9% - 200-250 ml and "Environment 199" 50-100 ml. At this time, the erythrocytes returned to the patient (scheme No. 1).

Immunofan 75-125 μg per 1x10 9 leukocytes is added to a vial with a leukocyte suspension. The resulting solution is incubated for 90 minutes at t 0 = 37 0 C in a thermostat, then re-centrifuged for 15 minutes at 1500 rpm. After centrifugation, the solution is removed from the vial to a buffy coat, the leukocytes are washed 3 times with a sterile saline solution of 200-300 ml, the washed leukocytes are diluted with 0.9% NaCl 50-100 ml and transfused into the patient intravenously.

We also provide more detailed information on the correction of immunity and new effective techniques in other sections of the monograph.

Extracorporeal treatment of leukocytes with immunophan

Hormone therapy

Corticosteroids are usually prescribed when septic shock is at risk. In such cases, prednisone 30-40 mg should be prescribed 4-6 times a day. When the clinical effect is achieved, the dose of the drug is gradually reduced.

In case of septic shock, prednisone should be administered at a dose of 1000-1500 mg per day (1-2 days), and then, when the effect is achieved, they switch to maintenance doses (200-300 mg) for 2-3 days. Effective in sepsis progesterone, which relieves the RES, increases renal function.

The introduction of anabolic hormones should be considered indicated, provided there is sufficient intake of energy and plastic materials in the body. The most applicable is retabolil (1 ml intramuscularly I-2 times a week).

Symptomatic therapy for sepsis

Symptomatic treatment includes the use of cardiac, vascular, analgesics, narcotic drugs, anticoagulants.

Given the high level of kininogens in sepsis and the role of kinins in microcirculation disorders, proteolysis inhibitors are included in the complex treatment of sepsis: gordox 300-500 thousand units, counterkal 150 thousand units per day, trasilol 200-250 thousand units, pantrikin 240-320 units (maintenance doses are 2-3 times less).

For pain - drugs, for insomnia or agitation - sleeping pills and sedatives.

With sepsis, abrupt changes in the hemostasis system (hemocoagulation) can be observed - hyper- and hypocoagulation, fibrinolysis, disseminated intravascular coagulation (DIC), consumption coagulopathy. If signs of increased intravascular coagulation are detected, it is advisable to use heparin in a daily dose of 30-60 thousand units intravenously, fraxiparin 0.3-0.6 ml 2 times a day, acetylsalicylic acid 1-2 g as a disaggregant.

In the presence of signs of activation of the anticoagulant fibrinolytic system, the use of protease inhibitors (contrycal, trasilol, gordox) is indicated. Contrikal is administered intravenously under the control of coagulogram at the beginning of 40 thousand units per day, and then daily for 20 thousand units, the course of treatment lasts 5 days. Trasilol is administered intravenously in 500 ml of isotonic solution at 10-20 thousand units per day. Inside appoint amben 0.26 g 2-4 times a day or intramuscularly 0.1 once a day. Aminocaproic acid is used in the form of a 5% solution in isotonic sodium chloride solution up to 100 ml. Other information on the correction of hemostasis is presented in the lecture "Hemostasis. Disseminated intravascular coagulation syndrome" (v.2).

To maintain cardiac activity (deterioration of coronary circulation and myocardial nutrition, as well as in septic lesions of the endo- and myocardium), cocarboxylase, riboxin, mildronate, preductal, ATP, isoptin, cardiac glycosides (strophanthin 0.05% - 1.0 ml , korglikon 0.06% -2.0 ml per day), large doses of vitamins (Vit. C 1000 mg per day, Vit. B 12 500 mcg 2 times a day).

In case of insufficient pulmonary ventilation (ARV), oxygen inhalation is used through nasopharyngeal catheters, and the tracheobronchial tree is sanitized. Measures are being taken to increase the airiness of the lung tissue and the activity of the surfactant: breathing under high pressure with a mixture of O 2 + air + phytancides, mucolytics. Vibration massage is shown.

If the phenomena of ARF persist, then the patient is transferred to mechanical ventilation (with VC 15 ml / kg, PO 2 70 mm Hg, PCO 2 50 mm Hg). Drugs (up to 60 mg of morphine) can be used to synchronize breathing. Ventilation with positive expiratory pressure is used, but before switching to it, it is imperative to compensate for the BCC deficit, because impaired venous return decreases cardiac output.

Serious attention in sepsis deserves the prevention and treatment of intestinal paresis, which is achieved by normalizing the water-electrolyte balance, rheological properties of the blood, as well as the use of pharmacological stimulation of the intestine (anticholinesterase drugs, adrenogangliolytics, potassium chloride, etc.). Effective is the infusion of 30% sorbitol solution, which, in addition to the stimulating effect on intestinal motility, increases the BCC, has a diuretic and vitamin-saving effect. It is recommended to introduce cerucal 2 ml 1-3 times a day intramuscularly or intravenously.

As our studies have shown, an effective treatment for intestinal paresis is prolonged ganglionic blockade with normotonia (pentamin 5% -0.5 ml intramuscularly 3-4 times a day for 5-10 days). Sympatholytics (ornid, britilium tosylate) and alpha-adrenolytics (pyrroxan, butyroxan, phentolamine) have a similar effect.

General patient care for sepsis

Treatment of patients with sepsis is carried out either in special intensive care wards equipped with resuscitation equipment, or in intensive care units. The doctor does not "lead" a patient with sepsis, but, as a rule, takes care of it. Thorough care of the skin and oral cavity, prevention of bedsores, daily breathing exercises are carried out.

A person with sepsis should receive food every 2-3 hours. Food should be high-calorie, easily digestible, varied, tasty, and high in vitamins.

The diet includes milk, as well as its various products (fresh cottage cheese, sour cream, kefir, yogurt), eggs, boiled meat, fresh fish, white bread, etc.

To combat dehydration and intoxication, septic patients should receive a large amount of fluids (up to 2-3 liters) in any form: tea, milk, fruit drink, coffee, vegetable and fruit juices, mineral water (narzan, borjomi). Enteral nutrition should be preferred if the gastrointestinal tract is functioning normally.

Are actively introduced into practice and should be used more widely a scale for assessing the severity of the patient's condition... For the purpose of prognosis in the treatment of sepsis and septic shock, in our opinion, the ARACNE II scale can be considered the most convenient for practical use. Thus, when assessed on the ARASNE II scale - 22 points, the mortality rate in septic shock is 50%, and against the background of ARASNE II - 35 it is 93%.

In a short lecture, it is not possible to present all the questions of such a capacious topic as sepsis. Some aspects of this problem are also given in other lectures mentioned above. There the reader will also find some sources of literature on this topic.

Main literature:

1. ACCP /SCCM.Consensus Conference on Definitions of Sepsis and MOF. Chicago, 1991.

2. Yudina S.M. Gapanov A.M. et al. // Vestn. Intensive Ter. - 1995.-N 5.-P. 23.

3. Anderson B. O., Bensard D. D., Harken A.N. // Surg. Gynec. Obstet. - 1991. - Vol. 172.- P. 415-424.

4. Zilber A. P. Medicine of critical conditions .- 1995.- Petrozavodsk, 1995.-359C.

5. Berg R. D., Garlington A.W. // Infect. and Immun. 1979 Vol. 23.- P. 403-411.

6. Ficher E. et al. // Amer. J. Physiol. 1991. Vol. 261.- P. 442-452.

7. Butler R. R. Jr. Et. Al. // Advans. Shock Res. 1982. Vol. 7.- P. 133-145.

8. // 9. // 10. Camussi G. et. al. // Diagn. Immunol. 1985 Vol. 3.- P. 109-188.

11. Brigham K. L. // Vascular Endothelium Physiological Basis of Clinical Problems // Ed. J. D. Catrovas. 1991. P. 3-11.

12. // 13. Palmer R. M. J., Ferrige A. G., Moncada S. Nitric oxide release accounts for the biological activity of endothelium - derived relaxing factor // Nature, 1987. - Vol. 327.-P. 524-526.

14. Nazarov I.P., Protopopov B, V. et al. // Anest. and reanimatol. - 1999.-N 1.-S. 63-68.

15. Kolesnichenko A.P., Gritsan A.I., Ermakov E.I. and others. Septic shock: aspects of pathogenesis, diagnosis and intensive care // Actual problems of sepsis.- Krasnoyarsk.-1997.

16. Knauss W. A. ​​et. al., 1991.

17. Yakovlev S.V. Problems of optimization of antibiotic therapy of nosocomial sepsis //Consilium

INTRODUCTION: Inadequate initial antibiotic therapy, defined as the lack of in vitro effect of an antimicrobial agent against an isolated pathogen responsible for the development of an infectious disease, is associated with an increase in morbidity and mortality in patients with neutropenic fever or severe sepsis. To reduce the likelihood of prescribing inadequate antibiotic therapy, recent international guidelines for the treatment of sepsis have suggested empiric therapy targeting gram-negative bacteria, especially when suspected pseudomonas infection. However, the authors of this recommendation are aware that "there is no study or meta-analysis that has convincingly demonstrated an excellent clinical result of a combination of drugs in a certain group of patients with individual pathogens."

Theoretical basis for prescribing combination therapy:

• an increase in the likelihood that at least one drug will be active against the pathogen;
• prevention of persistent superinfection;
• immunomodulatory non-antibacterial effect of the secondary agent;
• enhancement of antimicrobial action based on synergistic activity.

Unlike patients with febrile neutropenia, which has been repeatedly and well studied, no randomized studies of severe septic patients with increased capillary permeability syndrome and multiple organ failure have been conducted, in which the mechanisms of distribution and metabolism of antibiotics may be impaired.

The main objective of this study was to compare the effectiveness of combination therapy with two broad-spectrum antibiotics moxifloxacin and meropenem with meropenem monotherapy for multiple organ failure caused by sepsis.

METHODS: This was a parallel group, randomized, open-label study. There were 600 patients with criteria for severe sepsis or septic shock.

Monotherapy received 298 people - the first group, and combination therapy 302 - the second group. The study was conducted from October 16, 2007 to March 23, 2010 in 44 intensive care units in Germany. The number of patients evaluated in the monotherapy group was 273 and 278 in the combination therapy group.

In the first group, patients were prescribed intravenous administration of meropenem 1 g every 8 hours, in the second group, 400 mg moxifloxacin was added to meropenem every 24 hours. The duration of treatment was 7-14 days from inclusion in the study or until discharge from the intensive care unit or death, whichever happened first.

The main assessment criterion was the degree of multiple organ failure according to the SOFA (Sepsis-related Organ Failure) scale, which is a point scale in patients with septic syndrome who are in intensive care. The scale is more designed to quickly score and describe a range of complications than to predict the outcome of the disease. Condition score: from 0 to 24 points, higher values ​​indicate more pronounced multiple organ failure. Also, the evaluation criterion was mortality from all causes on days 28 and 90. The survivors were followed up for 90 days.

RESULTS: Among the 551 evaluated patients, there was no statistically significant difference in the mean SOFA score between the groups receiving meropenem and moxifloxacin (8.3 points at 95% CI, 7.8-8.8 points) and meropenem alone (7.9 points; 95% CI 7.5 - 8.4 points) ( R = 0,36).

There was also no statistically significant difference in mortality at 28 and 90 days.

By day 28, there were 66 deaths (23.9%, 95% CI 19.0% -29.4%) in the combination therapy group compared with 59 patients (21.9%, 95% CI 17.1% -27 , 4%) in the monotherapy group ( P = 0,58).

By day 90, there were 96 deaths (35.3%, 95% CI 29.6% -41.3%) in the combination therapy group compared to 84 (32.1%, 95% CI 26.5% -38, 1%) in the monotherapy group ( P = 0,43).

CONCLUSIONS: In adult patients with severe sepsis, combined treatment with meropenem with moxifloxacin compared with meropenem alone does not reduce the severity of multiple organ failure and does not affect outcome.

The material was prepared by Ilyich E.A.

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Inadequate initial antibiotic therapy, defined as the lack of in vitro effect of an antimicrobial agent against an isolated pathogen responsible for the development of an infectious disease, is associated with an increase in morbidity and mortality in patients with neutropenic fever or severe sepsis. To reduce the likelihood of prescribing inadequate antibiotic therapy, recent international guidelines for the treatment of sepsis have suggested empiric therapy targeting gram-negative bacteria, especially when pseudomonas infection is suspected. However, the authors of this recommendation are aware that "there is no study or meta-analysis that has convincingly demonstrated an excellent clinical result of a combination of drugs in a certain group of patients with individual pathogens."

Theoretical basis for prescribing combination therapy:

• an increase in the likelihood that at least one drug will be active against the pathogen;
• prevention of persistent superinfection;
• immunomodulatory non-antibacterial effect of the secondary agent;
• enhancement of antimicrobial action based on synergistic activity.

Unlike patients with febrile neutropenia, which has been repeatedly and well studied, no randomized studies of severe septic patients with increased capillary permeability syndrome and multiple organ failure have been conducted, in which the mechanisms of distribution and metabolism of antibiotics may be impaired.

The essence of research on the empirical treatment of sepsis

The main objective of this study was to compare the effectiveness of combination therapy with two broad-spectrum antibiotics moxifloxacin and meropenem with meropenem monotherapy for multiple organ failure caused by sepsis.

METHODS: A randomized, open-label, parallel group study was conducted. There were 600 patients with criteria for severe sepsis or septic shock.

Monotherapy received 298 people - the first group, and combination therapy 302 - the second group. The study was conducted from October 16, 2007 to March 23, 2010 in 44 intensive care units in Germany. The number of patients evaluated in the monotherapy group was 273 and 278 in the combination therapy group.

In the first group, patients were prescribed intravenous administration of meropenem 1 g every 8 hours, in the second group, 400 mg moxifloxacin was added to meropenem every 24 hours. The duration of treatment was 7-14 days from enrollment in the study or until discharge from the intensive care unit or death, whichever came first.

The main criterion for assessment was the degree of multiple organ failure according to the SOFA scale, which is a point scale in patients with septic syndrome. Condition score: from 0 to 24 points, higher values ​​indicate more pronounced multiple organ failure. Also, the evaluation criterion was mortality from all causes on days 28 and 90. The survivors were followed up for 90 days.

RESULTS: Among the 551 evaluated patients, there was no statistically significant difference in the mean SOFA score between the groups receiving meropenem and moxifloxacin (8.3 points at 95% CI, 7.8-8.8 points) and meropenem alone (7.9 points - 95% CI 7 , 5 - 8.4 points) (P = 0.36).

There was also no statistically significant difference in mortality at 28 and 90 days.

By day 28, there were 66 deaths (23.9%, 95% CI 19.0% -29.4%) in the combination therapy group compared with 59 patients (21.9%, 95% CI 17.1% -27 , 4%) in the monotherapy group (P = 0.58).

By day 90, there were 96 deaths (35.3%, 95% CI 29.6% -41.3%) in the combination therapy group compared with 84 (32.1%, 95% CI 26.5% -38, 1%) in the monotherapy group (P = 0.43).

CONCLUSIONS: In adult patients with severe sepsis, combined treatment with meropenem with moxifloxacin compared with meropenem alone does not lead to a decrease in the severity of multiple organ failure and does not affect the outcome.

Video:

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As much literature is devoted to antibiotic therapy of sepsis as to the problem itself related to the classification and definition of sepsis. Most of the newly developed antibiotics are definitely recommended for use in the treatment of sepsis. Recommendations are given, as a rule, the most general (the indication is septicemia !?), which introduces additional confusion in the antibiotic therapy regimens. The situation is further aggravated by the lack of a unified generally accepted classification of sepsis, and, accordingly, comparable treatment results.

The situation has changed dramatically over the past 10 years in connection with the introduction into clinical practice of the final documents of the Conciliation Conference, which have become widespread in practice. The use of terms such as systemic inflammatory response (SVR), sepsis, severe sepsis and septic shock made it possible to outline certain groups of conditions (quite conditional, of course, but nevertheless certain!) That require different approaches for their treatment, including including the differentiated use of antibiotic therapy regimens. Researchers were able to develop more or less general principles of antibiotic therapy for generalized inflammatory reactions in relation to its forms / phases (SVR, sepsis, severe sepsis, septic shock), to compare the effectiveness of therapy using different antibiotic regimens, to evaluate the results of treatment.

The development of the principles of evidence-based medicine and their widespread introduction into everyday clinical practice has led to the need to evaluate the various methods used to treat generalized inflammatory processes. The conducted studies suggest that the use of antibiotics in the treatment of sepsis is based on evidence of the I (most reliable) level. This allows us to consider the use of antibiotics in the treatment of sepsis, severe sepsis and septic shock as a necessary component, the effectiveness of which is not questioned.

Based on the definitions of sepsis adopted at the Conciliation Conference, we can say that the appearance of two or more symptoms of systemic inflammatory response syndrome (SIRS) should serve as a good reason for raising the question of the qualitative nature of SIRR, and, consequently, about the possible initiation of antibiotic therapy if there is an infectious process. ... First of all, it is necessary to prove (or exclude) the infectious nature of the systemic inflammatory response. This is often not an easy task. An approximate, far from complete, list of the main conditions that can lead to the development of clinical signs of a systemic inflammatory response is given below.

• Acute pancreatitis
• Spinal trauma
• Bleeding
• Lung embolism
• Diabetic ketoacidosis
• Myocardial infarction
• Systemic vasculitis
• Systemic lupus erythematosus
• Massive aspiration

Differential diagnostics in order to verify the qualitative nature of SSVR is becoming a matter of not at all academic sense, since the prescription of antibiotics not according to indications can cause significant, sometimes irreparable, damage. In order to finally establish the cause of the development of the systemic inflammatory reaction syndrome, it is necessary to take all available diagnostic measures, including a dynamic assessment of the blood test (an increase in leukocytosis, an increase in the "shift of the formula to the left"), the use of instrumental diagnostic methods (X-ray and ultrasound studies, etc.). In a number of cases, radionuclide studies turn out to be effective, as well as a new method that has not yet received wide clinical use in domestic medicine - the determination of the concentration of procalcitonin in the blood serum.

Verification of the infectious nature of the systemic inflammatory reaction in accordance with the decisions of the Conciliation Conference makes it possible to formulate a diagnosis of "sepsis", which accordingly requires the appointment of antibiotic therapy.

What principles should a doctor follow when choosing antibiotic therapy regimens?

The diagnosis "sepsis" (as interpreted by the 1991 Conciliation Conference), indicating the appearance of systemic signs of an infectious process, allows us to consider as sufficient various drugs of the "first" line both in the case of empirical therapy and with a verified pathogen. Identification of signs of organ failure (2 or more points on the SOFA scale), which indicates "severe sepsis", should make the doctor remember about antibiotics of the so-called "reserve", modern principles of "de-escalation therapy".

The development of multiple organ failure indicates an extremely severe violation of organ functions and body defense factors, which must be taken into account when choosing an appropriate antibacterial drug. In addition to the direct direct toxic effect on certain organs (aminoglycosides - kidneys, rifamycin - liver, etc.), this is directly related to the fact of the release of mediatosis inducers, which are the structural elements of the bacterial wall released during the decay of a bacterial cell. These include lipopolysaccharide (endotoxin) gram-negative and teichoic acid - gram-positive microorganisms. Their release during the decay or lysis of microorganisms can significantly increase organ dysfunction (primarily by affecting the cardiovascular system), which must be taken into account.

Of course, this remark applies to drugs that have a bactericidal effect. It should also be borne in mind that different antibacterial drugs have different effects on the release of lipopolysaccharide. This should also be taken into account when choosing a drug (Table 1).

Table 1

Antibiotic properties to increase or decrease the release of endotoxin

Regarding the choice of drug (s) in the treatment of septic shock, one must bear in mind everything that has already been said about "severe sepsis". It is only necessary to take into account even more the need to start immediately with "de-escalation therapy", as well as to select drugs with a minimum release of endotoxin. Currently, it can be considered that the only group of drugs that meet this requirement can be considered only carbapenems (imipenem, meropenem).

Thus, we can say that one of the main and most important principles of antibiotic therapy for sepsis is as follows: the more severe and more pronounced the generalized inflammatory response (SSWR, sepsis, severe sepsis, septic shock), the more effective and safe antibiotic should be used ...

Antibiotic therapy for sepsis is overwhelmingly empirical, especially at the beginning of treatment. It should be emphasized right away that the sampling of material for microbiological research (Gram staining of smears, various biological fluids and discharge from drains, etc.) should be carried out before the start of antibacterial therapy. Unfortunately, this is not always possible, especially when patients are transferred from one hospital to another. However, regardless of the previous therapy and the patient's condition, a new stage of treatment should begin with an assessment of the microbiological status.

The choice of a drug for empiric therapy is based on the organ approach (in which organ or system the infectious process is localized), the most likely causative agent according to clinical examination, as well as on the usual resident flora present in the affected organ. Based on the first principle, a drug is selected that has the highest tropism for the tissues involved in the infectious process - osteotropic drugs for osteomyelitis that penetrate the blood-brain barrier during infectious processes in the central nervous system, etc. the causative agent that caused the infectious process, complicated by generalization, is the leading determining factor. Having determined the group of drugs acting on a specific pathogen, a subsequent selection of drugs is performed depending on the severity of the generalized inflammatory reaction.

Determining the scheme of antibiotic therapy and making the choice of the appropriate antibiotic, we are always faced with the dilemma of what to choose, the option of monotherapy with a broad-spectrum drug (cheaper, less toxic, etc.) or combination therapy (narrower spectrum, fewer resistant strains, etc.). etc.)? In this regard, the following should be noted. Until now, there is no reliable evidence base on the benefits of a particular method of therapy. Therefore, it is likely that the choice of a particular therapy regimen (mono or combined) should remain the lot of the physician's experience and taste.

Thus, the choice of the drug for the therapy is carried out. We can say that the choice of a drug is the most crucial moment after the indications for antibiotic therapy have been formulated. This stage must be treated with extreme attention. Only taking into account all the factors affecting the course and effectiveness of antibiotic therapy will minimize its side effects and reduce the risk of failure.

The developing signs of the progression of the infectious process (persistent temperature, a shift in the leukocyte formula, etc.) should first of all direct the diagnostic process towards finding an answer to the question: where, at what stage, the infectious process began to develop in the wrong direction, which was predicted, and why is it possible? It should be noted that instead of posing the question in such a plane, in the overwhelming majority of cases, another task is posed - replacing one antibiotic with another due to the ineffectiveness of the first. And such replacements sometimes even take place several times a day.

Once again, I would like to remind you that the development (progression) of the infectious process against the background of the antibiotic therapy regimen selected taking into account all factors affecting this process in the overwhelming majority indicates inadequate surgical aid or the development of an undiagnosed complication, and not the ineffectiveness of the antibiotic. On the contrary, if a change in antibiotic therapy leads to a positive result, this indicates, first of all, that a mistake was made initially. These are important general principles that every antibiotic therapist should keep in mind.

Since there is no specific treatment for sepsis, therapy for all patients includes similar basic elements: replacement therapy for multiple organ failure, drainage of closed infected cavities, and appropriate antibiotic therapy.

ANTIMICROBIAL THERAPY

From the very beginning, it is necessary to send blood, urine and sputum for microbiological analysis. Based on the history and clinical data, sowing of discharge from wounds, ascitic, pleural and cerebrospinal fluid is necessary. The importance of microbiological testing for clarifying the diagnosis increases if samples are obtained before antibiotics are given, but in some circumstances this is almost impossible. For example, in a patient with sepsis, suspected meningitis, and focal neurologic abnormalities, it is desirable to have a CT scan before a lumbar puncture, but do not delay antibiotic therapy while waiting for the scan results. In such a situation, it is better to start empirical therapy, even if it may delay or complicate microbiological diagnosis. At the same time, in most other cases, it is advisable to introduce antibiotics in a timely manner outside of a critical situation. In fact, there is little to suggest an effect of antibiotics on the incidence of sepsis or the resulting mortality in the first few days of illness. Ultimately, however, ensuring adequate antibiotic coverage is important: among patients with sepsis who have not received adequate microbiological treatment, mortality is 10–20% higher than among those who have received specific treatment. Failure in antibiotic therapy may be the result of localization of the infection in an undrained, closed cavity (for example, with pleural empyema, abscess in the abdominal cavity), where the antibiotic does not penetrate, due to the resistance of the pathogen, the creation of an insufficient concentration of antibiotics, or simply insufficient time for reaction after the start of therapy. Clearly, drainage of closed, infected cavities is critical to healing.

Antibiotics should be selected based on the individual characteristics of the patient (for example, taking into account immunodeficiency, allergies and major chronic diseases), the expected "gateway of infection", the nature of the resistance of the local (nosocomial) flora to antibiotics and the study of the body's environments. The pH of the environment at the site of infection is of great importance. If the pathogen has not been identified with certainty, broad-spectrum antibiotics should be prescribed pending the results of the microbiological study. Unfortunately, the asymptomatic and widespread use of antibiotics in the past has led to an increase in the resistance of microorganisms to the prescribed drugs, so nowadays, the empirical antimicrobial therapy regimen often requires the appointment of two to three, sometimes even four antibiotics.

When no clear source of infection can be found, therapy with third-generation cephalosporins in combination with aminoglycosides is probably warranted. In many cases, vancomycin must also be added to this initial therapy (if pathogens such as penicillin-resistant Streptococci pneumoniae or Staphylococci, especially methicillin-resistant pathogens are common in the region).

Likewise, if there is a suspicion of the presence of an "atypical" organism causing pneumonia, it is prudent to add doxycycline or erythromycin. Finally, if there is a strong suspicion of the presence of anaerobic infection, metronidazole or clindamycin should be added. It is advisable to start therapy for a patient in serious condition with antibiotics with the widest spectrum of action, and then, as new clinical data become available, modify the therapy. For the same reasons, appointments should be re-analyzed daily and those that have become unnecessary should be promptly canceled. Contrary to popular belief, antibiotic therapy is not harmless. Excessive use is costly, exposes the patient to allergic reactions and drug toxicity and, perhaps more importantly, leads to the emergence of highly resistant strains of pathogens.

In the absence of diagnostic clinical data, the putative gateway of infection is probably the most useful information for antibiotic selection. For a detailed discussion of appropriate empirical treatment, see Chapter 26 Infection in the Intensive Care Unit. The spectrum of action of antibiotics should correspond to the individual patient's history. In 50-60% of patients with sepsis, the lungs are identified as the primary source of infection. They are followed by sources of intra-abdominal or pelvic localization (25-30% of patients), and about the same often the "gate of infection" cannot be established. The urinary tract, skin and central nervous system are somewhat less likely to serve as sites of primary localization. Obviously, when antibiotics are selected, their dosages must also be adjusted to suit the changing conditions of the kidneys and liver.

RESPIRATORY SUPPORT

Because of the high incidence of hypoxemic respiratory failure, a patient with sepsis usually requires tracheal intubation, supplemental oxygen, and mechanical ventilation. The specific features of maintaining airway patency, principles and problems of mechanical ventilation are discussed in detail in chapters 6-9; however, some unique features of sepsis-induced lung damage deserve further mention. More than 80% of patients eventually develop respiratory failure and require mechanical ventilation, and almost all patients require supplemental oxygen. Therefore, intubation should be planned for patients with sepsis, tachypnea (respiratory rate above 30 / min) and insufficient oxygenation. Rapid tachypnea and desaturation should not be expected to resolve on their own. Such tactics often end in emergency intubation of a patient with apnea, and few are able to maintain a breathing rate of more than 30 / min.

It is impossible to determine which ventilation method is optimal for a patient with sepsis, however, in the initial period of an unstable state, it makes sense to provide full support (assisted, controlled or intermittent mandatory ventilation [PPVL] with a frequency sufficient to provide more than 75% of the required minute ventilation) 1

Full support, especially for patients in shock, provides mechanical assistance that redistributes cardiac output from the respiratory muscles to other areas of the body. The result of ventilation support can be significant and in many cases increases the systemic oxygen delivery by 20% relative to the need for it.

Sometimes the respiratory center is so active that sedation has to be applied in order to coordinate the respiratory efforts of the person and the apparatus. Fortunately, muscle relaxants are rarely needed if adequate sedation is achieved and the respirator is carefully adjusted. To ensure the best synchronization and patient comfort, special attention should be paid to changes in the nature and speed of inspiratory gas flow and tidal volume.

There is no single parameter that determines the frequency of barotrauma during mechanical ventilation, but there is a pronounced relationship between barotrauma and transalveolar pressure exceeding 30-35 cm of water. Art. The near-maximum alveolar pressure of the respiratory cycle is best assessed clinically by plateau pressure if the chest wall is not very rigid. At present, there are enough data to justify the limitation of plateau pressure to 35 cmH2O. Art. in order to reduce the risk of overstretching of the lungs and the occurrence of barotrauma. This often requires a decrease in tidal volume to 5-6 ml / kg, which usually results in some hypercapnia.

1 This means that the characteristics of these modes are adjusted by the operator so that 75-80% of the required minute ventilation is provided by the ventilator.

In order to maintain acceptable arterial oxygen saturation (in most cases SaO2 above 88%), its content in the inhaled gas should be increased. The actual immediate risk of hypoxemia far outweighs the potential future risk of oxygen toxicity. Lower saturation values ​​are acceptable for a young, otherwise healthy patient, while higher saturation values ​​may be required in patients with critical organ perfusion deficiencies (eg, myocardial ischemia or recent stroke). Much is unclear about the problem of the potential toxicity of oxygen, but most often the goal is to reduce F, O2 to 0.6 or less while ensuring sufficient SaO2. If more F, O2 is required, PEEP is usually gradually increased. Apparently, it is true that the best value of PEEP is the lowest value that allows you to maintain full involvement of the lungs in ventilation and provides an acceptable delivery of O2 when F, O2 is below 0.6. Some minimal level of PEEP, increasing the FRU of the lungs and> minimizing damage caused by repeated phase opening and closing of the alveoli, is probably beneficial for all ventilated patients. In most cases, PEEP is 5-10 cm of water. Art. sufficient to achieve the above, but the optimal level to prevent reopening and collapse of the alveoli is unknown. (Recent evidence suggests that PEEP above 5 cm H2O may provide better protection for patients with ARDS - see Chapters 8 and 9.) F, O2 between 40 and 60% and PEEP 7-15 cm H2O. Art.

CARDIOVASCULAR SUPPORT

Septic shock in generalized infection is usually defined as a decrease in systolic blood pressure to less than 90 mm Hg. Art. or a decrease in normal systolic blood pressure by more than 40 mm Hg. Art., despite the infusion of fluid. At the onset of septic shock syndrome, most patients show a significant decrease in BCC with varying degrees of peripheral vascular dilatation and myocardial dysfunction. Left ventricular filling pressure is usually low because patients with sepsis have been deprived of food for some time, have increased fluid loss (due to sweating, shortness of breath, vomiting, or diarrhea), vasodilatation, and increased endothelial permeability. To optimize the filling of the left ventricle in an average patient with sepsis, it is required to inject from 4 to 6 liters of plasma-substituting crystalloids or a comparable amount of colloids that increase the BCC. In terms of efficiency, crystalloids and colloids are the same in this case. Obviously, less colloid is required, although in sepsis neither colloids nor crystalloids are completely retained in the vascular space. An increase in BCC with a low consumption of colloids is achieved at a higher cost; they cause allergic reactions, and the price is sometimes 20-100 times higher than the cost of an equivalent dose of crystalloids. Fluid is often given empirically initially, but when volumes have exceeded 2–3 L, a catheter is usually inserted into the pulmonary artery for monitoring. The only way to ensure adequate left ventricular preload is to directly measure the wedge pressure. (A less desirable alternative is to administer fluid until pulmonary edema develops.) Since myocardial compliance and transmural pressure are highly variable, the optimal left ventricular filling pressure for each patient must be empirically determined and often reassessed. As a rule, for this, hemodynamic parameters are measured several times a day, determining the response to sequential fluid administration.

The issue of cardiovascular support is discussed in detail in Chapter 3 (Treatment of Circulatory Failure), but several points deserve additional coverage. As a rule, vasopressor or cardiac stimulating agents are indicated for patients in whom the BCC is restored. In patients with insufficient volume, vasopressors are often ineffective and can be harmful if used in doses that compromise the perfusion of vital organs. In practice, most clinicians begin circulatory medication with a low dose of dopamine (less than 5 mcg / kg / min) and then gradually increase the infusion until the desired clinical result is achieved. The rationale behind this technique is based on the pharmacodynamics of dopamine. Low doses of dopamine are likely to have a P-adrenergic stimulating effect, increasing cardiac output. In addition, some dopaminergic effect is achieved, possibly improving renal blood flow.

When the doses are increased, the dopaminergic effect persists and at the same time the a-adrenergic effect is clinically manifested. Thus, dopamine can counteract septic suppression of the myocardium and increase too low systemic vascular resistance.

Some clinicians empirically add dobutamine to an existing vasopressor regimen, or substitute it for dopamine if cardiac output seems unacceptably low. When a deep decrease in systemic vascular resistance is responsible for hypotension and shock, it is also common practice to add an a-adrenergic stimulant (neosinephrine or norepinephrine) to the drug regimen. Contrary to the widespread belief that the use of powerful a-adrenergic agents "guarantees" an unfavorable outcome, sometimes only after the initiation of norepinephrine administration, the general peripheral vascular resistance (OPSR) increases, in turn increasing mean arterial pressure and organ perfusion. In some situations (for example, cor pulmonale), the inability to raise systemic blood pressure deprives the heart of the perfusion gradient that is required for pumping function.

Doctors and nurses sometimes have anxiety if a patient requires a higher dose of a particular vasoactive drug than was used in their past experience.

However, it should be borne in mind that individual sensitivity to vasopressors varies widely (possibly on a logarithmic scale), therefore, in shock, there are no absolute dose restrictions, however, when a very large number of vasoactive agents is required, several specific causes of persistent hypotension should be considered, in particular, a decrease in BCC. , adrenal insufficiency, profound acidosis, constrictive pericarditis or cardiac tamponade, and tension pneumothorax. In an effort to achieve a certain level of blood pressure, it is important to take into account the normal blood pressure for a given patient, the specific needs of the organs for perfusion and the clinical response to therapy.

Shock therapy should be aimed at ensuring normal brain activity, adequate diuresis (more than 0.5 ml / kg / h), sufficient blood supply to the skin and fingers and a reasonable level of oxygenation, and not at obtaining certain indicators of oxygen delivery, seizure pressure, arterial pressure or cardiac output. These clinical goals are usually achieved when cardiac output is in the range from 7 to 10 liters, the concentration of lactate in arterial blood decreases, and the oxygen transport rates are slightly higher than those for a healthy patient at rest.