Efficacy of empirical antibacterial treatment for severe sepsis. Algorithm for antimicrobial therapy of sepsis Modern treatment of sepsis

Treatment of septic patients should be carried out under constant clinical and laboratory monitoring, including assessment of general condition, pulse, blood pressure and central venous pressure, hourly diuresis, body temperature, respiratory rate, ECG, pulse oximetry. It should be mandatory to study general blood and urine tests, indicators of acid-base status, electrolyte metabolism, residual nitrogen, urea, creatinine, sugar, coagulogram (clotting time, fibrinogen content, platelets, etc.) in the blood. 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.

Comprehensive treatment of sepsis represents one of the most difficult tasks. Usually it consists of two main directions:

1.Active surgery primary and metastatic purulent foci.

2. General intensive treatment of a septic patient, the goal of which is rapid correction of homeostasis.

Surgical treatment of sepsis

Surgical treatment is aimed at removal of septic focus and is carried out for 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 pain relief method is gentle. Best conditions for inspection of the lesion, they are provided under intubation anesthesia (induction - seduxen, ketamine; main anesthesia - NLA, GHB, etc.).

Surgical treatment of a purulent focus must be carried out with mandatory compliance with a number of requirements:

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

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

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

By applying sutures under conditions of active drainage of the wound with its washing and vacuum aspiration or the “flow” method;

Treatment of the wound under a bandage with multicomponent ointments on a hydrophilic basis or draining sorbents;

Stitching the wound tightly (for limited indications);

Suturing in 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 neurotrophic effects, and tissue trauma.

When combining the suture of a purulent wound with active antibacterial drainage, washing the wound cavity with antiseptic solutions is carried out for 7-10 days every day for 6-12 hours, depending on the condition of the wound. The flow-aspiration drainage technique provides mechanical cleansing of the purulent focus from necrotic detritus and has a direct antimicrobial effect on the wound microflora. Rinsing usually requires 1-2 liters of solution (0.1% solution of dioxidin, 0.1% solution of furagin, 3% solution of boric acid, 0.02% solution of furatsilin, etc.). When treating purulent processes caused by clostridial microflora, solutions of hydrogen peroxide, potassium permanganate, and metrogil are used for rinsing. The washing method is accessible, technically simple, and applicable in any conditions. It should be noted that flushing drainage for anaerobic infection is less effective than for purulent infection, since it does not lead to a rapid reduction in excess tissue swelling.

Modern methods of actively influencing a purulent wound are aimed at sharply reducing the first and second phases of the wound process. The main objectives of wound treatment in the first (purulent-necrotic) stage of the wound process are suppression of infection, elimination of hyperosmia, acidosis, activation of the process of rejection of necrotic tissue, adsorption of toxic wound discharge. Thus, drugs for wound chemotherapy must 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 for 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.

Multicomponent ointments have been developed (levosin, levomikol, levonorsin, sulfamilon, dioxykol, sulfamekol), which include antimicrobials(levomycetin, norsulfazole, sulfadimethoxin, dioxidine), an activator of tissue metabolic processes (methyluracil), a local anesthetic (trimecaine), and the hydrophilic base of the ointment (polyethylene oxide) ensures its dehydrating effect in purulent wound. Due to hydrogen bonds, polyethylene oxide (PEO) forms complex compounds with water, and the connection between water and the polymer is not rigid: taking water from tissues, PEO relatively easily releases it into the gauze bandage. The ointment reduces interstitial hypertension and is capable of suppressing wound microflora after 3-5 days. The ointment lasts 16-18 hours, the bandage is usually changed daily.

In recent years, water-absorbing drainage sorbents such as “Sorbilex”, “Debrizan” (Sweden), “Galevin” (Russian Federation), and carbon adsorbents of granular and fibrous structure have found widespread use to influence the focus of purulent infection. Local application of drainage sorbents has an effective anti-inflammatory effect, accelerates wound healing processes and reduces treatment time. Dressings are performed daily; 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 at 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 lesions. The method is provided by a dialysis membrane drainage, in the cavity of which an osmoactive polymer gel is exchanged as a dialysis solution. Such drainage ensures dehydration of edematous inflammatory tissues and elimination of stagnation of wound exudate, has the ability to transmembranely absorb toxic substances from the wound (vasoactive mediators, toxic metabolites and polypeptides), and creates conditions for regional detoxification. At the same time, the introduction of antibacterial drugs into the dialysate ensures their entry and uniform diffusion from the drainage into the tissues of the pyaemic focus to suppress pathogenic microflora. The method simultaneously has antimicrobial, anti-inflammatory, anti-ischemic, detoxifying effects and creates optimal conditions for regenerative processes in the wound site.

Membrane dialysis drain functions like a miniature artificial kidney, and wound dialysis is essentially a method of intracorporeal regional detoxification, which prevents intoxication associated with a septic focus. There is a real opportunity to change the usual way 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 dialysing membrane drainage.

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

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

Intensive care of sepsis and septic shock

Based on 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 rehabilitation of a 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) Combating endotoxicosis and preventing MODS;

8) Correction of blood clotting disorders;

9) Suppression of the activity of mediators;

10) Immunotherapy;

11) Hormone therapy;

12) Nutritional support

13) General care for septic patients;

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 other infectious origins associated with fungi and viruses should not be missed. Most hospitals report cases of sepsis associated with Gr- and Gr+ bacteria, which are part of the normal microflora of the body.

Microbiological diagnostics sepsis is decisive in the selection of effective antibacterial therapy regimens. If the requirements for proper sampling of material are met, 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 adequate microbiological diagnosis of sepsis, the following rules should be observed.

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

2 . Blood for research is taken from a peripheral vein. Blood should not be drawn from the catheter unless catheter-associated sepsis is suspected.

3 . The required minimum 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 bottles with ready-made nutrient media, and not vials closed with cotton-gauze stoppers prepared in the laboratory.

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

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

Initial choice of starting imperial adequate therapy is one of the most significant factors determining the clinical outcome of the disease. Any delay in starting adequate antibacterial therapy increases the risk of complications and deaths. 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 antibacterial 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 susceptibility and situational assumption of infection (empirical treatment regimens). As mentioned above, strains of microorganisms in sepsis are often associated with hospital infection.

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

In most hospitals The use of broad-spectrum antibiotics and combinations of antibiotics is considered the rule, which ensures their high activity against a wide range of microorganisms before the results of microbiological testing become known (Table 1). Guaranteed broad spectrum infection suppression is the main reason for such antibacterial therapy. Another reason for using a combination of different types of antibiotics is the reduction in the likelihood of developing antibiotic resistance during treatment and the presence of synergism, which allows for rapid suppression of flora. The simultaneous use of several antibiotics in patients with threatened 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

Empirical therapy for sepsis

Characteristics of sepsis	Sepsis without PON	Severe sepsis with MODS
With an unknown primary focus In surgical departments In the RIT department For neutropenia	Cefotaxime 2 g 3-4 times a day (ceftriaxone 2 g 1 time 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 per 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 + aminoglycoside 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 daily 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; in the event of subsequent ineffectiveness, at the third stage, add antifungal drug(amphotericin B or fluconazole).

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. All of them have good effectiveness 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 in large daily doses. In patients with neutropenia, penicillin (mezlocillin) with increased activity against Pseudomonas aeruginosa in combination with aminoglycosides when administered several times a day are an effective remedy against hospital infections. Successfully used to treat sepsis imipenem and carbapenem.

Determining the optimal antibiotic regimen for patients with sepsis requires studies in large groups of patients. If Gr+ infection is suspected, vancomycin is often used. When determining the sensitivity of antibiotics, therapy may be changed.

Modern work focuses 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 are effective and safe in the treatment of severe bacterial infections.

There are a number of arguments in favor of choosing monotherapy. Its cost, as well as the frequency of adverse reactions, is lower. An alternative to combination therapy may 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 empiric therapy for severe sepsis with MODS are carbopenems (imipenem, meropenem) as drugs with the widest spectrum of activity, to which the lowest 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 the new class of oxazolidinones (linezolid) are not inferior to vancomecin in their activity against Gr+ microorganisms and have similar clinical efficacy.

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

table 2

Etiotropic therapy of sepsis

Microorganisms	1st line remedies	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 daily
Streptococcus pneumoniae	Cefotaxime 2 g 3 times a day Ceftriaxone 2 g once daily	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 daily	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 daily + amikacin 1 g daily 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 daily + amikacin 1 g daily Cefepime 2 g 3 times a day + amikacin 1 g daily
	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). When the lesion is on lower limbs, gives good results in the kidneys continuous arterial infusion antibiotics.

The drugs must be prescribed in courses of 2-3 weeks in medium and maximum doses, using 2-3 drugs simultaneously, administered in different ways (orally, intravenously, intra-arterially). The patient should not be prescribed an antibiotic that has already been used within 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 intratracheal through a bronchoscope or catheter.

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

They have proven themselves to be effective in the treatment of sepsis. sulfonamides drugs. It is advisable to use etazol sodium salt (1-2 g 2 times a day as a 10% solution intramuscularly or as a 3% solution 300 ml into a vein drip). However, their side and toxic effects are also known. In this regard, with the availability of modern highly effective antibiotics, sulfa drugs gradually lose their meaning. Drugs used to treat sepsis nitrofuran series- furodonin, furozolidone, and antiseptic dioxidin 1.0-2.0 g/day. Metronidazole has a wide spectrum of action against spore- and non-spore-forming anaerobes, as well as protozoa. However, its hepatotoxicity should be taken into account. It is prescribed intravenously at a dose 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, antikinin drugs should be included in therapy (contrical, trasylol 10-20 thousand units intravenously 2-3 times a day).

For prevention of superinfection(candidiasis , enterocolitis) must be used antimycotic drugs (nystatin, levorin, diflucan), eubiotics(mexase, mexaform). The destruction of normal intestinal microflora under the influence of antibiotics can lead to vitamin deficiency, because intestinal bacteria are producers of vitamins of group “B” and partly of group “K”. Therefore, along with antibiotics, they must be prescribed vitamins.

When taking antibiotic therapy, it is necessary to remember this possible complication, How exacerbation reaction, which is associated with increased breakdown of microbial bodies and the release of microbial endotoxins. Clinically, it is characterized by agitation, sometimes delirium, and increased temperature. Therefore, you should not start antibiotic treatment with so-called loading doses. Great importance To prevent these reactions, there is a 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

Progressive development of surgical infection with clinical point vision is, first of all, an increasing intoxication of the body, which is based on the development of severe microbial toxemia.

Under endogenous intoxication implies the entry from the source and accumulation in the body of various toxic substances, the nature and character of which is determined by the process. These are intermediate and final products of normal metabolism, but in elevated concentrations (lactate, pyruvate, urea, creatinine, bilirubin), products of unlimited proteolysis, hydrolysis of glycoproteins, lipoproteins, phospholipids, enzymes of the coagulation, fibrinolytic, kallikrikinin system, antibodies, inflammatory mediators, biogenic 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 severe in cases of septic multiple organ failure. in the stage of decompensation of the body’s internal detoxification mechanisms. Impaired liver function is associated with failure of the natural mechanisms of internal detoxification, renal failure implies 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 the entry of toxins from the primary affect. Intoxication is reduced as a result of opening and draining the purulent focus, due to the removal of pus along with microbial toxins, enzymes, tissue breakdown products, and biologically active chemical compounds.

However, practice shows that when in severe eudotoxemia, eliminating 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 when the primary source is completely eliminated. At the same time, traditional (routine) treatment methods are not able to break the pathogenetic links of severe endotoxicosis. The most pathogenetically justified in such a situation are methods of influence aimed at removing toxins from the body, which should be used against the backdrop of a full complex traditional therapy aimed at correcting all detected violations.

An integrated approach to the treatment of severe forms of surgical infection includes conservative and active surgical detoxification methods. Degree of endotoxemia 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.

Methods of complex detoxification for sepsis

IN early period Toxemia, with preserved diuresis, use conservative detoxification methods, including hemodilution, correction of acid-base balance, water-electrolyte metabolism, and forced diuresis.

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

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

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

Patients are usually administered 2000-2500 ml of various solutions per day. The amount of solutions administered intravenously and enterally is strictly controlled taking into account diuresis, fluid loss during vomiting, diarrhea, perspiration and hydration indicators (auscultation and radiography of the lungs, hematocrit, central venous pressure, bcc).

Enterosorption

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

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

Hyperbaric oxygenation

An effective method of combating local and general hypoxia in endotoxicosis is the use of hyperbaric oxygenation (HBO), which helps improve microcirculation in organs and tissues, as well as central and organ hemodynamics. At the core therapeutic effect HBOT is a significant increase in the oxygen capacity of body fluids, which allows you to quickly increase the oxygen content in cells that suffer from hypoxia as a result of severe endotoxicosis. HBOT increases the levels of humoral factors of nonspecific protection, stimulates an increase in the number of T- and B-lymphocytes, while the content of immunoglobulins significantly increases.

TO surgical detoxification methods All modern dialysis-filtration, sorption and plasmapheretic methods of extracorporeal hemocorrection for endotoxicosis should be included. All these methods are based on removing toxins and metabolites of various masses and properties directly from the blood, and allow for a reduction in endogenous intoxication. Surgical detoxification methods include:

1. Hemodialysis, ultrahemofiltration, hemodiafiltration.
2. Hemosorption, lymphosorption; immunosorption.
3. Therapeutic plasmapheresis.
4. Xenosplenperfusion.
5. Xenohepatic perfusion.
6. Flow ultraviolet irradiation of autologous blood.
7. Extracorporeal heme oxygenation.
8. Laser irradiation of autologous blood.
9. Peritoneal dialysis.

Main indication for use surgical methods detoxification is to determine the degree of toxicity of blood, lymph and urine with a high level 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 blood enzyme levels (ALT, AST, lactate dehydrogenase, cholinesterase, alkaline phosphatase, aldolase), metabolic or mixed acidosis, oligoanuria or anuria.

When planning extracorporeal hemocorrection for endotoxemia, 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 not enough to obtain a quick therapeutic effect. Hemodialysis removes electrolytes and low molecular weight substances. Ultrafiltration methods also remove liquid and medium-molecular toxins. The non-dialyzability of toxic substances through semi-permeable membranes serves as the basis for the use of sorption detoxification methods, which are aimed at removing mainly medium- and high-molecular substances. In case of high toxicity of blood plasma, the combination of hemodiafiltration and sorption methods with therapeutic plasmapheresis seems to be the most justified.

Hemodialysis (HD)

Hemodialysis is carried out using an artificial kidney machine. Dialysis is a process in which substances in solution are separated due to unequal diffusion rates through a membrane, since membranes have different permeability for substances with different molecular weights (membrane semi-permeability, dializability of substances).

In any embodiment, the “artificial kidney” includes the following elements: a semi-permeable membrane, on one side of which the patient’s blood flows, and on the other side - a saline dialysate solution. The heart of the “artificial kidney” is the dialyzer, a semi-permeable membrane in which plays the role of a “molecular sieve”, separating substances depending on their molecular sizes. The membranes used for dialysis have almost the same pore size of 5-10 nm and therefore can only pass through small molecules not associated with protein. To prevent blood clotting, anticoagulants are used in the device. In this case, thanks to transmembrane diffusion processes, the concentration of low molecular weight compounds (ions, urea, creatinine, glucose and other substances with low molecular weight) in the blood is equalized and dialysate, which ensures extrarenal blood purification. With an increase in the pore diameter of the semi-permeable membrane, the movement of substances with a higher molecular weight occurs. With the help of hemodialysis, it is possible to eliminate hyperkalemia, azotemia and acidosis.

The hemodialysis operation is very complex, requiring expensive and complex equipment, a sufficient number of trained medical personnel and the presence of special “kidney centers”.

It must be taken into account that in practice, with endotoxicosis, the situation often develops in such a way that toxins and cell breakdown products are mainly associated with proteins, forming a strong chemical complex that is difficult to remove. Hemodialysis alone in such cases, as a rule, cannot solve all problems.

Ultrafiltration (UV)

This is a 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 positive hydrostatic pressure in the dialyzer by partially compressing the venous line or by creating negative pressure on the outer surface of the membrane in the dialyzer. The filtration process under increased hydrostatic blood pressure simulates natural process glomerular filtration, since the renal glomeruli function as an elementary blood ultrafilter.

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 elimination of up to 2500 ml of ultrafiltrate. The resulting ultrafiltrate is replaced by Ringer's solution, glucose and plasma-substituting solutions.

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

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

Hemodiafiltration /GDF/

For enhanced detoxification, dehydration and correction of homeostasis, hemodiafiltration is used, combining simultaneous hemodialysis and hemofiltration. Dilution of blood using an 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. Clearance of urea, creatinine, and medium molecules is highest with this method of detoxification. The clinical effect consists of 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 is usually started by increasing the transmembrane pressure in the dialyzer without circulating the dialysate solution. 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, metabolites are thus removed 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 first scheme is most effective. With this method of hemodialysis it is usually possible to completely dehydrate the patient, reduce blood pressure and avoid collapse or hypertensive crisis at the end of dialysis.

"Artificial placenta"

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

Hemosorption

Hemoperfusion through activated carbon (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 (UAG-01, AGUP-1M, etc.) filled with a sterile sorbent. For this, uncoated activated carbons of the IGI and 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 carbon sorbents with blood-compatible materials significantly reduces injury shaped elements and reduces the absorption of blood proteins.

The column with the sorbent is connected to the patient’s circulatory system using an arteriovenous shunt. For external bypass surgery it is usually used radial artery and the most developed branch of the lateral and medial saphenous vein in the lower third of the forearm.

Heparinization is carried out at the rate of 500 units 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 (250 ml carbon volume) 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 within 45 minutes of hemocarboperfusion decreases from 8 to 5 meq/l, which significantly reduces the danger of the toxic effect of hyperkalemia on the heart and prevents intraventricular block and cardiac arrest in the diastole phase.

It is necessary to take into account that hemosorption is accompanied by injury to blood cells - the number of red blood cells, 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). The lymph is collected in a sterile vial and returned to the bloodstream by gravity, passing through a column with a sorbent (SKN carbon volume 400 ml), or a roller perfusion pump of the UAG-01 apparatus is used. Using the device allows you to quickly perform 2-3 times the perfusion of lymph through the sorbent in 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 new-generation sorbents, 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 an antigen (AG) or antibody (AT) fixed on an insoluble matrix as an affinity ligand. Upon contact with blood, the antigen fixed on the sorbents binds the corresponding antigens present in it; in the case of AT fixation, binding of complementary antigens occurs. The specificity of the interaction between AG and AT is extremely high and is realized at the level of correspondence of the active fragments of the AG molecule to a certain part of the AT macromolecule that 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 almost any compound that can be extracted from biological media. Low molecular weight substances that do not have antigenic properties are no exception.

Antibody immunosorbents are used for selective extraction of microbial toxins from the blood. The practical application of immunosorption will likely be extremely limited. high price immunosorbents.

Therapeutic plasmapheresis (TP)

The term "apheresis" (Greek) means removal, taking away, taking. Plasmapheresis ensures the separation of plasma from formed elements without injuring the latter and is today the most promising detoxification method 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 the blood plasma. Plasmapheresis allows only blood plasma to be subjected to detoxification treatment (sorption, ultraviolet irradiation, ILBI, sedimentation), returning formed blood cells to the patient.

Most often used discrete (fractional) centrifugal plasmapheresis. In this case, blood is exfused from the subclavian vein into a polymer container "Gemakon-500" with a preservative. The collected blood is centrifuged at 2000 rpm on a K-70 or TsL-4000 centrifuge for 10 minutes. The plasma is removed from the container. Red blood cells are washed twice in a 0.9% sodium chloride solution in a centrifuge for 5 minutes at 2000 rpm. The washed red blood cells are returned to the patient’s bloodstream. Plasma replacement is carried out with 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 plasma replaced must be greater than that removed. Fresh frozen plasma can quickly restore blood volume and oncotic pressure. It is a supplier of various blood coagulation factors, immunoglobulins, and is recognized as the most valuable physiological product. Typically, the patient undergoes 3-4 PF operations at intervals of 24 hours, with replacement not with saline solution, but with fresh frozen donor plasma.

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

Plasmapheresis using blood separators

Plasmapheresis is carried out on an Amnico device (USA) or other similar devices 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 a 10-20% albumin solution in an amount of 100-400 ml, a rheopolyglucin solution 400 ml, a 0.9% sodium chloride solution 400-1200. With good contouring of the peripheral veins, the cubital vein is punctured and the blood is returned to it.

Saccular plasmapheresis

It is produced using Gemakon-500/300 containers. Blood is withdrawn 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 an isotonic sodium chloride solution with 5000 IU of heparin is added to the cell suspension and injected into the patient. 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 a 10-20% albumin solution in an amount of 100-300 ml, a rheopolyglucin solution 400 ml , 0.9% sodium chloride solution 400-1200 ml.

Saccular cryoplasmpheresis

Plasma is collected in sterile 300 ml bags. Add 50 ml of isotonic sodium chloride solution to the remaining cell suspension and inject it into the patient.

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. The plasma is collected in 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.). During one procedure, 900-1500 ml of plasma is removed, which is replaced with the patient’s frozen plasma, prepared in the previous procedure.

Cryoplasmasorption

A cryoplasmapheresis procedure, in which the isolated plasma, cooled to 4 0 C, is passed through 2-3 columns with hemosorbent with a volume of 150-200 ml each, and then heated to 37 C and returned to the patient. Cryoproteins and other material adsorbed on activated carbon, deleted. In total, 2000-3500 ml of plasma is passed through the hemosorbent during the procedure.

The disadvantages of plasmapheresis are well known. Immunoglobulins, hormones and other biologically active compounds needed by the body are released along with the plasma. This must be taken into account in patients diagnosed with sepsis. But usually 2-4 sessions of plasmapheresis lead to a sustainable improvement in the patient’s condition.

Membrane plasmapheresis

Requires careful selection of the hemofilter dialysing membrane, namely the pore size. All toxic compounds have different molecular weights and require 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 makes it possible to preserve albumins and immunoglobulins in the body during plasmapheresis.

Xenosplenperfusion

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

This is a priority method of treating acute and chronic sepsis using short-term extracorporeal connection of the xenospleen to the patient’s blood vessels. Usually, in case of sepsis, complex detoxification (after sessions of hemosorption with membrane oxygenation, UV-autoblood, ILBI, plasmapheresis) to correct severe immunodeficiency includes ECPDS on days 4-6.

The pig spleen has found application as a powerful organ of immunological defense. Sterile, washed from the animal’s blood with saline, it not only actively absorbs microbes and toxins, but also releases biologically active substances into the purified blood of the patient, stimulating immune defense mechanisms.

The patient's blood is driven 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. Good effect The use of xenospleen is only possible in combination with conventional intensive therapy.

Extracorporeal perfusion of xenospleen slices

To avoid some complications during hemoperfusion through an organ (extravasation, blood loss, etc.), they resort to this method of immunocorrection and detoxification. The spleen is collected at a meat processing plant from healthy outbred pigs. In the operating room, under sterile conditions, sections 2-4 mm thick are made, followed by washing off 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 recirculation washing in 400 ml of physiological solution with the addition of 2000 IU of heparin. The perfusion system is then connected to the patient's blood vessels. The shunt is usually venovenous. The blood flow rate through the biosorbent is 80-100 ml/min for 0.5-1 hour.

Xenohepatic perfusion

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

An extracorporeal perfusion system is used using isolated living hepatocytes in an “auxiliary liver” device (AL). Isolated viable hepatocytes are obtained by the enzymatic-mechanical method from the liver of healthy piglets weighing 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. The plasma enters the oxygenator-heat exchanger, where it is saturated with oxygen and warmed to 37C; the plasma then 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 perfusion rate through the AVP for blood is 30-40 ml/min, for plasma 15-20 ml/min. Perfusion time is from 5 to 7.5 hours.

Hepatocytes in extracorporeal artificial perfusion support systems perform all liver functions; they are functionally active to well-known metabolites: ammonia, urea, glucose, bilirubin, “liver toxin”.

Flow ultraviolet irradiation of autologous blood

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

Using the devices "Isolda", FMK-1, FMR-10. BMR-120 irradiates the patient's blood with UV light for 5 minutes at a blood flow rate of 100-150 ml/min in a thin layer and sterile conditions. Blood is irradiated in a volume of 1-2 ml/kg. Typically, 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 FMC-1, one session is enough.

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

Extracorporeal membrane oxygenation (ECMO)

This is a method of assisted oxygenation 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 membrane oxygenators ("membrane lung") of a stationary type are used, which are connected to the arterial line of the heart-lung machine for the purpose of long-term auxiliary oxygenation.

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

Indications for starting ECMO are a decrease in PaO 2 levels below 50 mm Hg. Art. in patients with acute respiratory failure of polyetiological origin, and as a resuscitation measure in the treatment of terminal respiratory and circulatory disorders during hypoxic coma (PaO 2 below 33 mm Hg). In all patients, as a result of ECMO, PaO 2 can be significantly increased.

Low-flow membrane blood oxygenation (MO)

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

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

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

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

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 within 3 hours. In this situation, extracorporeal oxygenation of the liver portal system is very promising.

In this case, a capillary hemodialyzer of an artificial kidney is used to oxygenate the blood. Instead of dialysate fluid, oxygen gas is supplied to the column. The perfusion system with a dialyzer is connected to the patient’s vessels according to the scheme: superior vena cava - portal vein. The volumetric flow rate of blood in the system is maintained within 100-200 ml/min. The pO 2 level at the outlet of the oxygenator averages 300 mm Hg, art. The method allows you to support and restore impaired liver function.

Intravascular laser irradiation of autologous blood (ILBI)

For the purpose of nonspecific immunostimulation, laser irradiation of the patient's blood is performed (HNL - helium-neon laser). For ILBI, a physiotherapeutic laser unit 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, and increases the phagocytic activity of leukocytes.

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

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

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

Peritoneal dialysis (PD)

This is a method of accelerated detoxification of the body. The presence in the body of natural semi-permeable membranes, such as the peritoneum, pleura, pericardium, bladder, the basement membrane of the glomeruli of the kidneys and even the uterus, made it possible long ago to raise the question of the possibility and feasibility 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 of only historical interest, but the use of peritoneal dialysis for peritoneal dialysis, the so-called peritoneal dialysis, is successfully developing at the present time, sometimes competing in a number of parameters with hemodialysis or surpassing last.

However, this method is also not without significant drawbacks (primarily the possibility of developing peritonitis). Peritoneal dialysis is cheaper than hemodialysis, and many other detoxification methods. Exchange through the peritoneum is 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 capable of removing harmful toxic substances (protein-free nitrogen products, urea, potassium, phosphorus, etc.) from the body into the dialysate fluid introduced into the abdominal cavity. Peritoneal dipylysis 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 disturbances in water-salt metabolism, 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 (flowing) PD, performed through 2-4 rubber tubes inserted into the abdominal cavity. A sterile dialysate solution is continuously perfused through the peritoneal cavity at a flow rate of 1-2 L/hour;

2/ fractional (intermittent) PD - introduction of a portion of dialysate solution into the abdominal cavity with its change after 45-60 minutes.

Isotonic is used as a dialysate solution. saline solutions, balanced in blood plasma, with antibiotics and novocaine. To prevent fibrin deposition, 1000 units of heparin are added. The possibility of overhydration with cardiac overload and pulmonary edema due to the absorption of water into the blood is dangerous. Strict control over the amount of fluid introduced and removed is necessary.

The dialysate includes sodium bicarbonate or sodium acetate, which has buffering properties and allows you to maintain the pH within the required limits throughout 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 remove up to 1-1.5 liters of resorbed fluid. However, only 12-15% of toxic substances are removed.

The use of albumin in the dialysate significantly increases the effectiveness of PD. The process of nonspecific sorption of toxic substances on the protein macromolecule is activated, which makes it possible to maintain a significant concentration gradient between the plasma and the dialysate solution until the surface of the adsorbent is completely saturated (“protein dialysis”).

Dimethosmolarity of the dialysate fluid is of great importance for the successful implementation of PD. The osmotic pressure of 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 dialysate temperature should be 37-38C. 5000 units of heparin are injected into each liter of solution; to prevent infection, up to 10 million units of penicillin or other antibacterial agents are injected into the solution.

The use of extracorporeal detoxification methods is indicated against the background of hemodynamic stabilization. In the early stages of septic shock, it is possible to perform hemosorption or prolonged low-flow hemofiltration; in the future, it is possible to use plasmapheresis in combination with other methods of physiohemotherapy (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 repeatedly. Based on this, injections of killed bacteria have been used as vaccines for various types of fever. Apparently, this technique can be used for prevention 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 administration of endotoxin was noted.

At one time it was suggested that the use corticosteroids should be beneficial in sepsis as they may reduce the inflammatory response in cases of SIRS, which may improve outcome. However, these hopes were not realized. Careful clinical testing at two large centers found no beneficial effects of steroids in septic shock. This issue is highly controversial. It can be said that with our current state of provision medicinal substances we simply do not have other drugs to stabilize and reduce membrane permeability. TNF antagonists, monoclonal antibodies, IL-1 receptor antagonists, 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 a lot to be learned and put into practice.

Considering the hyperergic reaction of the sympatho-adrenal system and adrenal glands, the disruption of the body’s cytokine balance with the powerful release of a large number of mediators in response to aggression, and the resulting imbalance of all parts of homeostasis, it is necessary to use methods that allow blocking or compensating for the above processes. One such method is anti-stress therapy (AST).

It is fundamentally important to begin 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 preventable. The AST method we developed involves the combined use of an A2-adrenergic receptor agonist clonidine, neuropeptide dalargina and calcium antagonist isoptine. The use of AST is advisable in patients whose condition severity is more than 11 points according to APACHE 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 this background they efficiency increases).

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

An integral component of intensive care for sepsis is circulatory support 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 or vasoconstrictors(thromboxane A2, leukotrienes, catecholamines, angiotensin II , endothelin), or vasodilators(NO-relaxing factor, cytokinins, prostaglandins, platelet activating factor, fibronectins, lysosomal enzymes, serotonin, histamine).

In the 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 hepatorenal and splenic zone 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, sustained hypotension and MOF.

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

The first remedy in this situation is usually volume replenishment. If blood pressure continues to be low after volume replacement, blood pressure is used to increase cardiac output. dopamine or dobutamine If hypotension persists, correction can be made adrenaline. A decrease in the sensitivity of adrenergic receptors occurs when various forms 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), increased vascular resistance (alpha-adrenergic effect) and blood flow to the kidneys (dopaminergic effect). The adrenergic vasopressor effect of epinephrine may be required in patients with persistent hypotension on dopamine or in those who respond only to high doses of dopamine. For refractory hypotension, NO factor antagonists can be used. Methylene blue (3-4 mg/kg) has this effect.

It should be noted that the given treatment regimen for septic shock is not always effective. In this case, it is necessary again carefully evaluate objective hemodynamic parameters and volemia (cardiac output, stroke volume, central venous pressure, heart rate, blood volume, blood pressure, heart rate), accurately navigate the existing hemodynamic disorders (cardiac, vascular insufficiency, hypo- or hypervolemia, combined disorders) and carry out intensive care correction for a specific patient in a specific time period (inotropic drugs, vasoplegics, vasopressors, infusion media, etc.). Always consider reperfusion syndrome that arises during the treatment of 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, the successful recovery of patients from septic shock is facilitated by additional careful use of small doses of gangliolytics. Thus, usually fractional (2.2-5 mg) or drip administration of pentamine at a dose of 25-30 mg in the first hour significantly improves peripheral and central hemodynamics and eliminates hypotension. These positive effects additional therapy with gangliolytics are associated with an increase in the sensitivity of adrenergic receptors to endogenous and exogenous catecholamines and adrenergic agonists, improved microcirculation, inclusion of previously deposited blood in the active blood flow, a decrease in resistance to cardiac output, an increase in cardiac output 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 microcirculation normalizes, especially if its disturbances have been 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 has allowed us to more successfully cope with septic shock at various 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 indicators homeostasis. It is carried out in all patients with sepsis, taking into account the severity of intoxication, the degree of volemic disorders, disorders of protein, electrolyte and other types of metabolism, and the state of the immune system.

Main tasks infusion therapy are:

1 . Detoxification of the body using forced diuresis and hemodilution. For this purpose, 3000-4000 ml of Ringer's polyionic solution and 5% glucose are administered intravenously at the rate of 50-70 ml/kg per day. Daily diuresis is maintained within 3-4 liters. In this case, monitoring of central venous pressure, blood pressure, and diuresis is necessary.

2 . Maintaining the electrolyte and acid-base state of the blood. In sepsis, hypokalemia is usually observed due to the loss of potassium through the wound surface and in the urine (daily loss of potassium reaches 60-80 mmol). The acid-base state can change, both towards alkalosis and acidosis. The 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 (CBV).

4 . Correction of hypoproteinemia and anemia. Due to increased protein consumption and intoxication, the protein content in patients with sepsis is often reduced to 30-40 g/l, the number of erythrocytes to 2.0-2.5 x 10 12 / l, with the HB level below 40-50 g/l . Daily transfusion of high-grade protein preparations (native dried plasma, albumin, protein, amino acids), fresh heparinized blood, red blood cells, and washed red blood cells is necessary.

5 . Improving peripheral circulation, blood rheological parameters and preventing platelet aggregation in capillaries. For this purpose, it is advisable to transfuse intravenously rheopolyglucin, hemodez, and prescribe heparin 2500-5000 units 4-6 times a day; orally prescribed as a disaggregant - acetylsalicylic acid (1-2 g per day) together with vikalin or quamatel under the control of coagulogram, platelet count and their aggregation ability.

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

Approximate scheme of infusion-transfusion therapy in patients with sepsis (ITT volume - 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, KS1-1.5 g, NaCl- 1.0 g

6) Ringer's solution 500.0

7) Reambirin 400.0

II. Protein preparations:

8) solutions of amino acids (alvesin, aminon, etc.) - 500.0

9) protein 250.0

10) freshly citrated blood, erythrocyte suspension - 250-500.0 every other day

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

11) KS1 solution 1% - 300.0-450.0

12) sodium bicarbonate 4% solution (calculation based on base deficiency).

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

At anemia It is necessary to carry out regular transfusions of freshly preserved blood and erythroplasty. 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. Breathing support eases the load on the oxygen delivery system and reduces the oxygen cost of breathing. Gas exchange improves due to better oxygenation of the blood.

Enteral nutrition should be prescribed as early as possible (even before peristalsis is fully restored), in small portions (with 25-30 ml) or drip-flowing balanced humanized infant formula, or Spasokukkotsky’s mixture or special balanced nutritional mixtures (“Nutrizon”, “Nutridrink”, etc.). If it is impossible to swallow, administer mixtures through a nasogastric tube, incl. via NITK. The rationale for this may be: a) food, being a physiological irritant, triggers peristalsis; b) full parenteral compensation is impossible in principle; c) by triggering peristalsis, we reduce the chance of intestinal bacterial translocation.

Oral administration or tube administration should be carried out after 2-3 hours. If discharge through the tube increases or belching or feeling of fullness occurs, skip 1-2 injections; if not available, increase the volume to 50 - 100 ml. It is better to administer nutritional mixtures through a tube by drip, which increases the effectiveness of nutritional support and avoids these complications.

Balance and overall caloric intake should be checked daily; from the 3rd day after surgery it should be at least 2500 kcal. The deficiency in composition and caloric intake must be compensated by intravenous administration of solutions of glucose, albumin, and fat emulsions. It is possible to administer 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 " C" at least 1 g/day and the entire 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 outlet colon.

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

Immunity correction methods

Passive and active immunization occupies an important place in the treatment of patients with sepsis. Both nonspecific 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 a day), hyperimmune plasma (antistaphylococcal, antipseudomonas, anticolibacillary), whole blood or its fractions (plasma, serum, or leukocyte suspension) from immunized donors (100 -200ml).

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

Carrying out active specific immunization (with toxoid) in the acute period of sepsis should be considered unpromising, since it requires the production of antibodies. long time(20-30 days). In addition, it should be taken into account that the septic process develops against a background of extremely strained or already depleted immunity.

In chronic sepsis or during the recovery period in acute sepsis, the administration of active immunization agents - toxoids, autovaccines - is indicated. Anatoxin is administered in 0.5-1.0 ml doses at intervals of three days.

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

In case of sepsis, a differentiated approach to the correction of immune deficiency is necessary, depending on the severity of immune disorders and SIRS. Immunotherapy is necessary for patients in whom the need for intensive care arose against the background of a chronic inflammatory process, with a history of predisposition to various inflammatory diseases (probable chronic immunodeficiency) and with severe SIRS.

Regardless of the severity of the condition, nonspecific biogenic stimulants are indicated: metacil, mildronate or mumiyo. Normalizes the ratio of cells of the main classes of T-lymphocyte subpopulations, activates the early stages of antibody genesis and promotes maturation and differentiation immunocompetent cells extracorporeal immunopharmacotherapy with immunofan. 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 to a more early dates. The method of combined use of stress-protective, adaptagen therapy and efferent detoxification methods is as follows. After patients are admitted to the intensive care unit with the start of infusion therapy, the neuropeptide dalargin 30 mcg/kg/day or instenon 2 ml/day is administered intravenously.

When positive CVP values ​​are achieved, in order to reduce the hyperergic stress reaction, stabilize hemodynamics and correct metabolism, intensive care includes clonidine at a dose of 1.5 mcg/kg (0.36 mcg/kg/hour) intravenously 1 time per day, in parallel continuing infusion therapy. After patients recover from septic shock, to continue neurovegetative protection, pentamine is administered intramuscularly at a dose of 1.5 mg/kg/day, 4 times a day during the catabolic stage of sepsis. The bioprotector mildronate is prescribed intravenously from days 1 to 14 at a dose of 7 mg/kg/day once a day; actovegin - intravenous drip 1 time per day, 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 over 10 days. Plasmapheresis begins in patients with severe sepsis after stabilization of hemodynamics; in other cases in the presence of endotoxemia of II-III degree.

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

After blood collection, sodium hypochlorite is introduced 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 red blood cells, 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 administered in the same quantity.

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 this, the plasma is cooled to +4, +6 0 C 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 freezer at a temperature of -14 0 C. A day later, the patient undergoes 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. If there are positive blood cultures, it is better not to return the exfused plasma to the patient.

For the purpose of correcting secondary immunodeficiency, preventing bacterial and septic complications, it shows high effectiveness method of extracorporeal processing of leukocytes immunofan. The method of extracorporeal treatment of leukocytes with immunofan is as follows.

Donor blood is taken through the central venous collector in the morning in an amount of 200-400 ml. Heparin is used as an anticoagulant at a rate of 25 units/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. The buffy coat is collected in a sterile vial and diluted with 0.9% NaCl solution - 200-250 ml and "Media 199" 50-100 ml. At this time, the red blood cells were returned to the patient (scheme No. 1).

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

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 immunofan

Hormone therapy

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

In case of septic shock, prednisolone should be administered at a dose of 1000-1500 mg per day (1-2 days), and then, when the effect is achieved, switch to maintenance doses (200-300 mg) for 2-3 days. Progesterone is effective for sepsis, which unloads the RES and increases kidney function.

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

Symptomatic treatment of sepsis

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

Considering 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, contrical 150 thousand units per day, trasylol 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, sudden changes in the hemostatic 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 daily dose 30-60 thousand units intravenously, fraxiparine 0.3-0.6 ml 2 times a day, acetylsalicylic acid 1-2 g as a disaggregant.

If there are signs of activation of the anticoagulant fibrinolytic system, the use of protease inhibitors (contrical, trasylol, gordox) is indicated. Contrical is administered intravenously under the control of a coagulogram at the beginning of 40 thousand units per day, and then daily at 20 thousand units, the course of treatment lasts 5 days. Trasylol is administered intravenously in 500 ml of isotonic solution, 10-20 thousand units per day. Ambien is prescribed orally at 0.26 g 2-4 times a day or intramuscularly at 0.1 g once a day. Aminocaproic acid is used in the form of a 5% solution in an 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” (vol. 2).

To maintain cardiac activity (deterioration of coronary circulation and myocardial nutrition, as well as in case of septic lesions of the endo- and myocardium), cocarboxylase, riboxin, mildronate, preductal, ATP, isoptin, cardiac glycosides (strophanthin 0.05% - 1.0 ml) are administered , korglykon 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 (APV), 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 indicated.

If the symptoms of ARF persist, then the patient is transferred to mechanical ventilation (with vital capacity 15 ml/kg, PO 2 70 mm Hg, RSO 2 50 mm Hg). To synchronize breathing, you can use drugs (up to 60 mg of morphine). Mechanical ventilation with positive expiratory pressure is used, but before switching to it, it is necessary to compensate for the deficit of blood volume, because impaired venous return reduces cardiac output.

In case of sepsis, the prevention and treatment of intestinal paresis deserves serious attention, 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.). An effective infusion is a 30% sorbitol solution, which, in addition to stimulating intestinal motility, increases blood volume and has a diuretic and vitamin-saving effect. It is recommended to administer cerucal 2 ml 1-3 times a day intramuscularly or intravenously.

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

General care for patients with sepsis

Treatment of patients with sepsis is provided either in special intensive care wards equipped with resuscitation equipment, or in intensive care units. The doctor does not “manage” a patient with sepsis, but, as a rule, nurses him. Careful care of the skin and oral cavity, prevention of bedsores, and daily breathing exercises are provided.

A patient with sepsis should receive food every 2-3 hours. Food should be high in calories, easily digestible, varied, tasty, and containing a large amount of vitamins.

The diet includes milk, as well as various of its 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 liquids (up to 2-3 liters) in any form: tea, milk, fruit juice, coffee, vegetable and fruit juices, mineral water (Narzan, Borjomi). Preference should be given to enteral nutrition provided that the gastrointestinal tract is functioning normally.

They are being actively introduced into practice and should be used more widely scales for assessing the severity of the condition of patients. For the purpose of prognosis in the treatment of sepsis and septic shock, in our opinion, the APACHE II scale can be considered the most convenient for practical use. So, when assessed on the APACHE II scale - 22 points, mortality in septic shock is 50%, and against the background of APACHE II - 35 it is 93%.

It is not possible to present all the issues of such a capacious topic as sepsis in a short lecture. Certain 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. and others // Vestn. Intensive Ter.- 1995.-N 5.-C. 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. and others // Anest. and resuscitation - 1999.-N 1.-pp. 63-68.

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

16. Knauss W. A. ​​et. al., 1991.

17. Yakovlev S.V. Problems of optimizing antibacterial therapy for nosocomial sepsis //Consilium

INTRODUCTION: Inadequate initial antibiotic therapy, defined as the lack of in vitro effect of an antimicrobial against the isolated causative agent, is associated with increased morbidity and mortality in patients with neutropenic fever or severe sepsis. To reduce the likelihood of inappropriate antibiotic therapy, recent international guidelines for the treatment of sepsis have suggested empiric therapy targeting Gram-negative bacteria, especially in suspected cases. pseudomonas infection. However, the authors of this recommendation are aware that “there is not a single study or meta-analysis that would conclusively demonstrate superior clinical outcome of a combination of drugs in a specific group of patients for specific pathogens.”

Theoretical basis for prescribing combination therapy:

• increasing the likelihood that at least one drug will be active against the pathogen;
• preventing the occurrence of persistent superinfection;
• immunomodulatory non-antibacterial effect of the secondary agent;
• enhancing the antimicrobial effect based on synergistic activity.

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

Main goal this study was a comparison of 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 study in parallel groups. 600 patients with criteria for severe sepsis or septic shock participated.

298 people received monotherapy - the first group, and 302 people received combination therapy - the second group. The study was carried out from October 16, 2007 to March 23, 2010 in 44 intensive care units in Germany. The number of patients evaluated was 273 in the monotherapy group 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 moxifloxacin 400 mg was added to meropenem every 24 hours. The duration of treatment was 7 to 14 days from study entry or until discharge from the intensive care unit or death, whichever occurred first.

The main evaluation criterion was the degree of multiple organ failure according to the SOFA (Sepsis-related Organ Failure) scale, which is a scoring scale for patients with septic syndrome in intensive care. The scale is more intended for quick scoring and description of a number of complications than for predicting the outcome of the disease. Condition assessment: from 0 to 24 points, higher values ​​indicate more severe multiple organ failure. Also, the evaluation criterion was mortality from all causes at 28 and 90 days. Survivors were monitored for 90 days.

RESULTS: Among 551 patients evaluated, there was no statistically significant difference in mean SOFA score between the meropenem and moxifloxacin groups (8.3 points; 95% CI, 7.8 to 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).

At 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, combination treatment with meropenem and moxifloxacin, compared with meropenem monotherapy, does not reduce the severity of multiple organ failure and does not affect the 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 against the isolated causative agent, is associated with increased morbidity and mortality in patients with neutropenic fever or severe sepsis. To reduce the likelihood of inappropriate antibiotic therapy, recent international guidelines for the treatment of sepsis have suggested empirical therapy targeting Gram-negative bacteria, especially when pseudomonas infection is suspected. However, the authors of this recommendation are aware that “there is not a single study or meta-analysis that would conclusively demonstrate superior clinical outcome of a combination of drugs in a specific group of patients for specific pathogens.”

Theoretical basis for prescribing combination therapy:

• increasing the likelihood that at least one drug will be active against the pathogen;
• preventing the occurrence of persistent superinfection;
• immunomodulatory non-antibacterial effect of the secondary agent;
• enhancing the antimicrobial effect based on synergistic activity.

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

The essence of the study of empiric 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. 600 patients with criteria for severe sepsis or septic shock participated.

298 people received monotherapy in the first group, and 302 received combination therapy in the second group. The study was carried out from October 16, 2007 to March 23, 2010 in 44 intensive care units in Germany. The number of patients evaluated was 273 in the monotherapy group 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 moxifloxacin 400 mg was added to meropenem every 24 hours. The duration of treatment was 7–14 days from study entry or until discharge from the intensive care unit or death, whichever occurred first.

The main evaluation criterion was the degree of multiple organ failure according to the SOFA scale, which is a scoring scale for patients with septic syndrome. Condition assessment: from 0 to 24 points, higher values ​​indicate more severe multiple organ failure. Also, the evaluation criterion was mortality from all causes at 28 and 90 days. Survivors were monitored for 90 days.

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

At 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, combination treatment of meropenem with moxifloxacin compared with meropenem monotherapy does not reduce the severity of multiple organ failure and does not affect the outcome.

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The same large amount of literature is devoted to the issues of antibacterial therapy of sepsis as to the problem itself associated with the classification and definition of sepsis. Most newly developed antibiotics are necessarily recommended for use in the treatment of sepsis. Recommendations are given, as a rule, the most general (indication - septicemia!?), which introduces additional confusion into antibacterial therapy regimens. The situation is further aggravated by the lack of a single generally accepted classification of sepsis, and, accordingly, comparable treatment results.

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

The development of the principles of evidence-based medicine and their widespread implementation in everyday clinical practice has led to the need to evaluate various methods, used for the treatment of generalized inflammatory processes. The studies conducted suggest that the use of antibiotics in the treatment of sepsis is based on level I (the most reliable) evidence. 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 Consensus Conference, we can say that the appearance of two or more symptoms of systemic inflammatory response syndrome (SIRS) should serve as a compelling basis for raising the question of the qualitative nature of SIRS, and, consequently, 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 reaction. 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 injury
• Bleeding
• Pulmonary embolism
• Diabetic ketoacidosis
• Myocardial infarction
• Systemic vasculitis
• Systemic lupus erythematosus
• Massive aspiration

Carrying out differential diagnostics in order to verify the qualitative nature of SIRS becomes a completely non-academic issue, since prescribing antibiotics off-label can cause significant, sometimes irreparable, damage. In order to definitively establish the cause of the development of systemic inflammatory response syndrome, it is necessary to undertake all available measures. diagnostic measures, including dynamic assessment of blood tests (increasing leukocytosis, increasing “shift of the formula to the left”), use instrumental methods diagnostics (x-ray and ultrasound examinations, etc.). In a number of cases, radionuclide studies are effective, as well as a new method that has not yet received widespread clinical use in domestic medicine - determining the concentration of procalcitonin in blood serum.

Verification of the infectious nature of the systemic inflammatory reaction in accordance with the decisions of the Consensus Conference makes it possible to formulate a diagnosis of sepsis, which accordingly requires the prescription of antibacterial therapy.

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

The diagnosis of “sepsis” (in the interpretation of the 1991 Consensus Conference), indicating the appearance of systemic signs of an infectious process, allows us to consider various “first” line drugs to be sufficient both in the case of empirical therapy and in the case of a verified pathogen. Identification of signs of organ failure (2 or more points on the SOFA scale), which indicates “severe sepsis,” should force the doctor to remember the so-called “reserve” antibiotics and 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 the appropriate antibacterial drug. In addition to the 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 disintegration of the bacterial cell. These include lipopolysaccharide (endotoxin) of gram-negative microorganisms and teichoic acid - gram-positive microorganisms. Their release during the decay or lysis of microorganisms can significantly increase organ dysfunction (primarily affecting the cardiovascular system), which must be taken into account.

Of course, this remark applies to drugs that have a bactericidal effect. Please also keep 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

The properties of antibiotics to enhance or weaken the release of endotoxin

Regarding the choice of drug(s) for the treatment of septic shock, one must keep 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 select drugs with minimal 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 antibacterial therapy for sepsis is the following: the more severe and more pronounced the generalized inflammatory reaction (SIRS, sepsis, severe sepsis, septic shock), the more effective and safe the antibiotic should be used .

Antibacterial therapy for sepsis is overwhelmingly empirical, especially at the beginning of treatment. It must be immediately emphasized that the collection of material for microbiological examination (Gram staining of smears, various biological fluids and drainage discharge, 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 previous therapy and the patient’s condition, a new stage of treatment should begin with an assessment of the microbiological status.

The choice of drug for empirical therapy is based on the organ approach (in which organ or system the infectious process is localized), the most likely pathogen according to the data 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 tissues involved in the infectious process - osteotropic drugs for osteomyelitis, penetrating the blood-brain barrier during infectious processes in the central nervous system, etc. When choosing antibacterial drug, we must remember that it is the nature of the pathogen that caused the infectious process, complicated by generalization, that is the leading, determining factor. Having determined the group of drugs that act on a specific pathogen, a subsequent selection of drugs is made depending on the severity of the generalized inflammatory reaction.

When determining an antibacterial therapy regimen and choosing the appropriate antibiotic, we are always faced with the dilemma of what to choose: monotherapy with a broad-spectrum drug (cheaper, less toxic, etc.) or combination therapy (narrower spectrum, fewer resistant strains, etc.). d.)? In this regard, the following should be noted. To date, there is no reliable evidence base on the benefits of this or that method of therapy. Therefore, the choice of one or another therapy regimen (mono or combined) should probably remain a matter of the doctor’s experience and taste.

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

Developing signs of progression of the infectious process (persistent temperature, shift leukocyte formula etc.) must first of all direct the diagnostic process towards finding an answer to the question: where, at what stage did the infectious process begin to develop in a direction other than that which was predicted, and why did this become possible? It should be noted that instead of posing the question precisely in this plane, in the vast majority of cases, another task is posed - replacing one antibiotic with another due to the ineffectiveness of the first. And such replacements sometimes occur even several times a day.

Once again, I would like to remind you that the development (progression) of an infectious process against the background of an antibacterial therapy regimen chosen, taking into account all the factors influencing this process, overwhelmingly indicates inadequate surgical care or the development of an undiagnosed complication, and not the ineffectiveness of the antibiotic. On the contrary, if a change in antibacterial therapy leads to a positive result, this primarily indicates that a mistake was initially made. These are important general principles that every physician administering antibiotic therapy 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, culture of wound discharge, ascites, pleural and cerebrospinal fluid is necessary. The value of microbiological testing to clarify the diagnosis increases if samples are obtained before the start of antibiotic administration, but in some circumstances this is practically impossible. For example, in a patient with sepsis, suspected meningitis, and focal neurological impairment, it is advisable to perform a CT scan before a lumbar puncture, but do not delay antibiotic therapy while awaiting scan results. In such a situation it is better to start empirical therapy, even if it may delay or complicate microbiological diagnosis. However, in most other cases it is advisable to administer 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 syndrome or its associated mortality in the first few days of illness. Ultimately, however, ensuring adequate antibiotic coverage is important: patients with sepsis who do not receive microbiologically appropriate treatment have a 10% to 20% higher mortality rate than those who do. specific treatment. Failure of antibiotic therapy may be the result of localization of the infection in an undrained, closed cavity (for example, pleural empyema, abdominal abscess) where the antibiotic does not penetrate, a consequence of pathogen resistance, the creation of insufficient concentrations of antibiotics, or simply insufficient time for a reaction after initiation of therapy. Clearly, drainage of closed infected cavities is critical to cure.

Antibiotics should be selected based on the individual characteristics of the patient (for example, taking into account immunodeficiency, allergies and underlying chronic diseases), the expected “portal of infection”, the nature of resistance of the local (nosocomial) flora to antibiotics and the study of body environments. The pH of the environment at the site of infection is of great importance. If the causative agent is not identified with certainty, broad-spectrum antibiotics should be prescribed until the results of a microbiological study are obtained. 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 at present, the regimen of empirical antimicrobial therapy often requires the prescription of two or three, sometimes even four antibiotics.

When a clear source of infection cannot be found, therapy with a third-generation cephalosporin in combination with an aminoglycoside is probably warranted. In many cases, vancomycin should also be added to this initial therapy (if pathogens such as penicillin-resistant Streptococci pneumoniae or Staphylococci, especially methicillin-resistant Staphylococci, are common in the area).

Likewise, if an “atypical” pneumonia-causing organism is suspected, it is reasonable to add doxycycline or erythromycin. Finally, if anaerobic infection is strongly suspected, metronidazole or clindamycin should be added. It is advisable to start therapy for the patient at in serious condition antibiotics with the broadest spectrum of action, and then modify therapy as new clinical data become available. For the same reasons, appointments should be re-evaluated daily and promptly cancel those that have become unnecessary. Contrary to popular belief, antibiotic therapy is not harmless. Excessive use is costly, exposes patients 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 suspected "gateway of infection" probably provides the most useful information for antibiotic selection. Detailed discussion of relevant empirical treatment See Chapter 26, Infection in the Intensive Care Unit. The spectrum of action of antibiotics must correspond to the individual patient's medical 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 approximately as 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 doses must also be adjusted to the changing condition of the kidneys and liver.

RESPIRATORY SUPPORT

Because of the high incidence of hypoxemic respiratory failure, patients with sepsis usually require tracheal intubation, supplemental oxygen, and mechanical ventilation. Specific features of maintaining airway patency, principles and problems of mechanical ventilation are discussed in detail in Chapters 6-9; however, several unique features of sepsis-induced lung injury deserve additional 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 greater than 30/min) and insufficient oxygenation. Rapidly developing 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 withstand a respiratory rate of more than 30/min.

It is not possible to determine which method of ventilation is optimal for a patient with sepsis, but in the initial period of instability, it makes sense to provide full support (assisted, controlled, or intermittent mandatory ventilation [IMV] at 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 away from the respiratory muscles and toward other areas of the body. The effect of ventilatory support can be dramatic and in many cases increases systemic oxygen delivery relative to oxygen demand by 20%.

Sometimes the respiratory center is so active that sedation must be used to match the breathing efforts of the person and the machine. Fortunately, muscle relaxants are rarely necessary if appropriate sedation is achieved and the respirator is carefully adjusted. To ensure the best synchronization and comfort of the patient, you need to pay special attention to changes in the nature and speed of the inspiratory gas flow and tidal volume.

There is no single parameter that determines the frequency of barotrauma during mechanical ventilation, however, there is a clear connection between barotrauma and transalveolar pressure exceeding 30-35 cmH2O. Art. The near maximum alveolar pressure of the respiratory cycle is best assessed clinically by plateau pressure unless the chest wall is very rigid. Currently, there is enough data to justify limiting the plateau pressure to 35 cm of water. Art. in order to reduce the risk of lung overextension and barotrauma. This often requires a reduction 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.

To maintain acceptable arterial oxygen saturation (in most cases, SaO2 is above 88%), its content in the inspired gas should be increased. The actual immediate risk of hypoxemia greatly outweighs the potential future risk of oxygen toxicity. Lower saturation values ​​are acceptable in a young, otherwise healthy patient, whereas higher saturation values ​​may be required in patients with critical organ perfusion deficiency (eg, myocardial ischemia or recent stroke). There is much uncertainty about the potential for oxygen toxicity, but the most common goal is to reduce F,O2 to levels of 0.6 or less while providing sufficient SaO2. If more F,O2 is required, PEEP is usually increased gradually. Apparently, it is true that the best PEEP value is the smallest value that allows you to maintain full involvement of the lungs in ventilation and ensures acceptable O2 delivery at F, O2 below 0.6. Some minimum level of PEEP, by increasing lung FRC and minimizing damage caused by repetitive phasic opening and closing of the alveoli, is likely beneficial for all patients undergoing mechanical ventilation. In most cases, PEEP is 5-10 cm water. Art. sufficient to achieve the above, but the optimal level to prevent alveoli from reopening and collapsing is unknown. (The latest data suggest that PEEP above 5 cm of water column can provide better protection for patients with ARDS - see chapters 8 and 9.) Despite all the searches for the ideal combination of PEEP and F, O2, in practice, most patients with ARDS receive F, O2 between 40 and 60% and PEEP 7-15 cm H2O. Art.

CARDIOVASCULAR SUPPORT

Septic shock during generalized infection is usually defined as a decrease in systolic blood pressure to less than 90 mmHg. Art. or a decrease in normal systolic blood pressure by more than 40 mmHg. Art., despite fluid infusion. At the onset of septic shock syndrome, most patients experience a significant decrease in blood volume with varying degrees of dilatation peripheral vessels and myocardial dysfunction. Left ventricular filling pressures are usually low because patients with sepsis have been deprived of food for periods of time, have increased fluid loss (due to sweating, dyspnea, vomiting, or diarrhea), dilated vascular capacitance, and increased endothelial permeability. To optimize left ventricular filling, the average patient with sepsis needs to administer 4 to 6 liters of plasma-substituting crystalloids or a comparable amount of bcc-enhancing colloids. In terms of effectiveness, 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 small 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 initially administered empirically, but when volumes transfused exceed 2–3 L, a catheter is usually placed invasively into the pulmonary artery for monitoring. The only way to ensure adequate left ventricular preload is to directly measure wedge pressure. (A less desirable alternative is to administer fluid until pulmonary edema develops.) Because myocardial compliance and transmural pressure are highly variable, the optimal left ventricular filling pressure for each patient must be determined empirically and reassessed frequently. As a rule, this is done by measuring hemodynamic parameters several times a day to determine 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 pacemaker drugs are indicated for patients whose blood volume has been restored. In volume-depleted patients, vasopressors are often ineffective and may cause harm if used in doses that compromise vital organ perfusion. In practice, most clinicians begin drug circulatory support with a low dose of dopamine (less than 5 mcg/kg/min) and then gradually increase the infusion until the desired clinical response is achieved. The meaning of this technique is based on the pharmacodynamics of dopamine. Low doses of dopamine appear to have a P-adrenergic stimulatory effect, increasing cardiac output. In addition, some dopaminergic effect is achieved, possibly improving renal blood flow.

When doses are increased, the dopaminergic effect persists and at the same time the α-adrenergic effect is clinically manifested. Thus, dopamine can counteract septic myocardial depression and increase systemic vascular resistance that is too low.

Some clinicians empirically add dobutamine to or replace dopamine with an existing vasopressor regimen if cardiac output appears unacceptably low. When a profound decrease in systemic vascular resistance is responsible for hypotension and shock, it is also common practice to add an α-adrenergic stimulant (neosynephrine or norepinephrine) to the drug regimen. Contrary to the popular belief that the use of potent α-adrenergic drugs “guarantees” an unfavorable outcome, sometimes only after the start of norepinephrine administration does general peripheral vascular resistance (TPVR) increase, in turn increasing mean arterial pressure and organ perfusion. In some situations (eg, cor pulmonale), failure to raise systemic arterial pressure deprives the heart of the perfusion gradient required for pumping function.

Doctors and nurses sometimes become concerned if a patient requires a larger dose of a particular vasoactive drug than has been used in their past experience.

However, it should be borne in mind that individual sensitivity to vasopressors varies widely (possibly on a logarithmic scale), so in shock there are no absolute dosage limits, however, when very large quantities of vasoactive agents are required, several specific causes of persistent hypotension must be considered, in particular a decrease in volumetric volume , adrenal insufficiency, profound acidosis, constrictive pericarditis or cardiac tamponade, and tension pneumothorax. When trying to achieve a certain blood pressure level, it is important to take into account the patient's normal blood pressure, specific organ perfusion requirements, and clinical indicators of 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, wedge pressure, arterial pressure or cardiac output. These clinical goals are usually achieved when cardiac output is in the range of 7 to 10 L, arterial lactate concentrations are reduced, and oxygen transport rates are slightly above normal resting values.