Effectiveness of empirical antibiotic treatment for severe sepsis. Antibiotic therapy Initial empiric antibiotic therapy for sepsis

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

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

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

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

Surgical treatment of sepsis

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

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

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

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

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

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

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

Sewing up the wound tightly (for limited indications);

Suturing under conditions of transmembrane wound dialysis.

4. In all cases, after surgical treatment, it is necessary to create conditions of rest in the area of \u200b\u200bthe wound by immobilization to eliminate pain impulses, negative neuro-trophic influences, and tissue trauma.

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

Modern methods of active exposure to a purulent wound are aimed at a sharp reduction in the first and second phase of the early process. The main tasks of treating wounds in the first (purulent-necrotic) stage of the wound process are suppression of infection, elimination of hyperosmia, acidosis, activation of the process of rejection of necrotic tissues, adsorption of toxic wound discharge. Thus, drugs for chemotherapy of a wound 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 in the treatment of purulent wounds; Any hypertonic solutions have an extremely short-term effect on a purulent wound (no more than 2-8 hours), since they are quickly diluted with wound secretions and lose their osmotic activity. In addition, these solutions (antiseptics, antibiotics) have a certain damaging effect on the tissues and cells of the macroorganism.

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

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

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

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

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

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

Intensive care for sepsis and septic shock

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

1) Early diagnosis and sanitation of the septic focus;

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

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

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

6) Intestinal decontamination;

7) Fight against endotoxicosis and prevention of PON;

8) Correction of blood clotting disorders;

9) Suppression of the activity of mediators;

10) Immunotherapy;

11) Hormone therapy;

12) Nutritional Support

13) General care of a septic patient;

14) Symptomatic therapy.

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

Microbiological diagnostics sepsis is decisive in the choice of effective antibiotic therapy regimens. If the requirements for the correct 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 in another 24-48 hours to obtain an accurate identification of the pathogen.

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

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

2 ... Blood for research is taken from a peripheral vein. Blood sampling from a catheter is not allowed, except in cases where 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 vials with ready-made culture media, rather than vials closed with cotton-gauze stoppers prepared in the laboratory.

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

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

The initial choice of starting imperial adequate therapy is one of the most significant factors determining the clinical outcome of the disease. Any delay in initiating adequate antibiotic therapy increases the risk of complications and 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 antibiotic therapy in patients with severe sepsis should be carried out at the earliest stage of treatment (J. Cohen, W. Lynn. Sepsis, 1998; 2: 101)

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

Correct choice antimicrobial agents usually determined by the following factors: and) probable pathogen and its sensitivity to antibiotics , b) the underlying disease and the patient's immune status, in) pharmacokinetics of antibiotics , g) the severity of the disease, e) evaluation of the cost / effectiveness ratio.

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

Table 1

Empiric therapy for sepsis

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

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

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

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

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

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

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

table 2

Etiotropic therapy for sepsis

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

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

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

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

Worked well in the treatment of sepsis sulfonamide drugs. It is advisable to use the sodium salt of etazole (1-2 g 2 times a day in the form of a 10% solution intramuscularly or in the form of a 3% solution of 300 ml in a vein drip). However, their side and toxic effects are also known. In this regard, in the presence of modern highly effective antibiotics, sulfa drugs are gradually losing their importance. In the treatment of sepsis, drugs are used nitrofuran series - furodonin, furozolidone, and antiseptic dioxidine 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 considered. Prescribe it intravenously drip of 0.5 g every 6-8 hours.

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

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

With antibiotic therapy, it is necessary to remember about such a possible complication as exacerbation reaction, which is associated with increased breakdown of microbial bodies and the release of microbial endotoxins. Clinically, it is characterized by agitation, sometimes delirium, fever. Therefore, antibiotic treatment should not be started with so-called shock doses. Great importance to prevent these reactions has 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

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

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

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

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

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

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

Comprehensive detoxification methods for sepsis

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

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

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

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

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

Enterosorption

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

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

Hyperbaric oxygenation

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

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

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

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

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

Hemodialysis (HD)

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

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

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

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

Ultrafiltration (UV)

It is a process of separation and fractionation of solutions, in which macromolecules are separated from 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, the removal of fluid from the blood is carried out by creating a positive hydrostatic pressure in the dialyzer by partially clamping the venous line or creating negative pressure on the outer surface of the membrane in the dialyzer. The filtration process under increased hydrostatic blood pressure mimics the natural glomerular filtration process, since the 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 actively dehydrate the body of the excretion pathways up to 2500 ml of ultrafiltrate. The resulting ultrafiltrate is replaced by Ringer's solution, glucose and plasma-substituting solutions.

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

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

Hemodiafiltration / HDF /

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

"Dry dialysis"

In this case, hemodialysis usually begins with increasing the transmembrane pressure in the dialyzer without circulating dialysate fluid. After the required amount of fluid has been removed from the patient, the transmembrane pressure is reduced to a minimum and the dialysate supply is turned on. In the remaining time, thus, the metabolites are excreted from the body without removing water. Isolated ultrafiltration can also be performed at the end of dialysis or mid-treatment, but the former is most effective. With this method of hemodialysis, it is usually possible to fully 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 blood from one patient flows to one side of the membrane, while another patient sends his blood to the same membrane, only from the opposite side. Any low molecular weight toxins or metabolites can be transferred between subjects, one of which is a patient, without crossing the elements of the immuno-chemical system of each patient. In this way, a patient with acute reversible failure can be supported during the critical period by dialysis blood from a healthy donor with well-functioning natural mechanisms of internal detoxification (for example, a healthy mother can support her child).

Hemosorption

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

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

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

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

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

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

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

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

Lymphosorption

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

Immunosorption

Immunosorption refers to extracorporeal methods of immunocorrection and detoxification.

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

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

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

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

Therapeutic plasmapheresis (PF)

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

Most commonly 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 taken blood is centrifuged at 2000 rpm in a K-70 or TsL-4000 centrifuge for 10 minutes. Plasma is removed from the container. Erythrocytes are washed twice in 0.9% sodium chloride solution in a centrifuge for 5 minutes at 2000 rpm. The washed erythrocytes return to the patient's bloodstream. Plasma substitution is carried out by hemodez, rheopolyglucin, native donor single-group plasma and other infusion media.

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

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

Plasmapheresis using blood separators

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

Saccular plasmapheresis

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

Saccular cryoplasmapheresis

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

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

Cryoplasma sorption

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

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

Membrane plasmapheresis

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

Xenosplenoperfusion

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

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

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

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

Extracorporeal perfusion of xenospleen slices

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

Xenohepatoperfusion

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

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

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

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

Flowing ultraviolet irradiation of autologous blood

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

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

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

Extracorporeal membrane oxygenation (ECMO)

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

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

The principle of a 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 fixed in plastic cylinders that are blown with oxygen according to the counterflow principle.

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

Low-flow membrane oxygenation of blood (MO)

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

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

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

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

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

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

Intravascular laser irradiation of autologous blood (ILBI)

For the purpose of non-specific immunostimulation, laser irradiation of the patient's blood is 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 activation of the immune response, gives a pronounced analgesic, anti-inflammatory and hypocoagulant effect, increases the phagocytic activity of leukocytes.

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

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

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

Peritoneal dialysis (PD)

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

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

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

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

There are two types of PD:

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

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

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

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

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

Of great importance for the successful conduct of PD is the metosmolarity of the dialysis fluid. The osmotic pressure of the extracellular fluid and blood plasma is 290-310 mosm / l, so the osmotic pressure of the dialysate should be at least 370-410 mosm / l. The temperature of the dialysate should be 37 -38C. In each liter of solution, 5,000 U of heparin is injected, to prevent infection, up to 10 million U of penicillin or other antibacterial agents are injected into the solution.

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

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

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

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

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

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

An integral component of 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, either vasoconstrictors (thromboxane A2, leukotrienes, catecholamines, angiotensin II , endothelin), or vasodilators (NO-relaxing factor, cytokinins, prostaglandins, platelet activating factor, fibronectins, lysosomal enzymes, serotonin, histamine).

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

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

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

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

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

Infusion-transfusion therapy for sepsis

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

The main tasks infusion therapy are:

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

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

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

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

5 ... Improvement of peripheral blood circulation, rheological parameters of blood and prevention of platelet aggregation in capillaries. For this purpose, it is advisable to infuse intravenously rheopolyglucin, hemodez, prescribe heparin at 2500-5000 IU 4-6 times a day; orally appoint as a disaggregant - acetylsalicylic acid (1-2 g per day) together with vicalin 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 indicators of homeostasis. Therapy requires catheterization of the subclavian vein. It is convenient, as it allows not only to administer drugs, but also to take blood samples repeatedly, measure CVP, and monitor the adequacy of treatment.

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

I. Colloidal solutions:

1) polyglucin 400.0

2) hemodez 200.0 x 2 times a day

3) rheopolyglucin 400.0

B. Crystalloid solutions:

4) glucose 5% - 500.0 "

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

6) Ringer's solution 500.0

7) Reambirin 400.0

II. Protein preparations:

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

9) protein 250.0

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

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

11) KC1 solution 1% - 300.0-450.0

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

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

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

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

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

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

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

Contraindications to oral or tube feeding are: acute pancreatitis, nasogastric tube discharge\u003e 500 ml, NITC discharge\u003e 1000 ml.

Immunity correction methods

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Immunofan 75-125 μg per 1x10 9 leukocytes is added to a vial with a leukocyte suspension. The resulting solution is incubated for 90 minutes at t 0 \u003d 37 0 C in a thermostat, then re-centrifuged for 15 minutes at 1500 rpm. After centrifugation, the solution is removed from the vial to a buffy coat, the leukocytes are washed 3 times with a sterile saline solution of 200-300 ml, the washed leukocytes are diluted with 0.9% NaCl 50-100 ml and intravenously transfused into 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 immunophan

Hormone therapy

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

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

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

Symptomatic therapy for sepsis

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

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

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

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

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

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

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

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

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

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

General patient care for sepsis

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

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

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

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

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

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

Main literature:

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

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

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

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

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

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

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

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

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

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

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

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

16. Knauss W. A. \u200b\u200bet. al., 1991.

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

Send your good work in the knowledge base is simple. Use the form below

Students, graduate students, young scientists using the knowledge base in their studies and work will be very grateful to you.

Posted on http://www.allbest.ru/

Justification of regimens of empirical antimicrobial therapy for sepsis

The empirical choice of antibacterial drugs dictates the need to use antibiotics with a fairly wide spectrum of activity already at the first stage of treatment, sometimes in combination, given the extensive list of potential pathogens with varying sensitivity. With the localization of the primary focus in the abdominal cavity and oropharynx, one should also imply the participation of anaerobic microorganisms in the infectious process. A more definite judgment about the etiology of sepsis is possible in cases of bacteremia after splenectomy and catheter-associated bacteremia.

Another important parameter that determines the program of initial empiric therapy for sepsis is the severity of the disease. Severe sepsis, characterized by the presence of multiple organ failure (MOF), has a higher mortality rate and more often leads to the development of terminal septic shock. The results of antibiotic therapy for severe sepsis with PON are significantly worse compared to sepsis without PON, therefore, the use of the maximum regimen of antibiotic therapy in patients with severe sepsis should be carried out at the earliest stage of treatment (evidence category C).

Since the earliest possible use of adequate antibiotic therapy reduces the risk of death, therefore, the efficacy factor should dominate the cost factor.

§ the spectrum of suspected pathogens depending on the localization of the primary focus (see Table 7 on p. 50);

§ the level of resistance of nosocomial pathogens according to microbiological monitoring data1;

§ conditions for the onset of sepsis - community-acquired or nosocomial;

§ the severity of the infection, assessed by the presence of multiple organ failure or the APACHE II scale.

In the treatment programs below, antibacterial drugs are ranked into two tiers - 1st line (optimal) and alternative drugs.

Means of the 1st row are antibiotic therapy regimens, the use of which, from the standpoint of evidence-based medicine and according to experts, allows achieving a clinical effect with the highest probability. This also took into account the principle of reasonable sufficiency, i.e. whenever possible, antibiotics with a narrower spectrum of antimicrobial activity were recommended as the means of choice.

Antibacterial agents are classified as alternatives, the effectiveness of which in this pathology has also been established, but they are recommended in the second place for various reasons (cost, tolerance, level of resistance) and are prescribed if the first line agents are unavailable or intolerant.

Sepsis with an unidentified focus of infection

The rational choice of the regimen of antibiotic therapy for sepsis is determined not only by the localization of the source (focus) of the infection, but also by the conditions of infection (community-acquired or nosocomial). If there is reason to assume the out-of-hospital nature of the infection, then the drugs of choice may be third-generation cephalosporins (cefotaxime, ceftriaxone) or fluoroquinolones. Among the latter, drugs of a new generation (levofloxacin, moxifloxacin), which have a higher activity against gram-positive bacteria, have an advantage. It is also permissible to use second generation cephalosporins or protected aminopenicillins (amoxicillin / clavanate, ampicillin / sulbactam) in combination with aminoglycosides (gentamicin, netilmicin). Given the high probability of abdominal sources of infection, it is advisable to combine cephalosporins and levofloxacin with metronidazole. In severe community-acquired sepsis with PON and the patient's critical condition (APACHE II more than 15 points), the most effective therapy regimen will be with the maximum broad spectrum: carbapenem (imipenem, meropenem, ertapenem), or IV generation cephalosporin cephapim in combination with metronidazole, or fluoroquinolones last generation (levofloxacin + metronidazole or moxifloxacin).

When choosing an adequate treatment regimen for nosocomial sepsis, it is necessary to plan not only the coverage of all potential pathogens, but also the possibility of participation in the infectious process of multi-resistant hospital strains of microorganisms. It is necessary to take into account the wide distribution in medical institutions of our country (especially in multidisciplinary emergency hospitals, ICU) of methicillin-resistant staphylococci, some enterobacteria (Klebsiella spp., E. colt) - producers of extended-spectrum p-lactamases (which is accompanied by a decrease in the effectiveness of cephalosporins and often aminogli and fluoroquinolones), Pseudomonas aeruginosa, resistant to gentamicin, ciprofloxacin, inhibitor-protected penicillins. At present, we must admit that carbapenems (imipenem, meropenem) are the optimal mode of empiric therapy for severe nosocomial sepsis with PON as drugs with the widest spectrum of activity, to which the lowest level of resistance among nosocomial strains of gram-negative bacteria is noted. In some situations, cefepime, protected antipseudomonadia | 3-lactams (cefoperazone / sulbactam, piperacillin / tazobactam), and ciprofloxacin in adequate doses are a worthy alternative to carbapenems. In case of ineffectiveness of these regimens of therapy, the advisability of additional administration of vancomycin or linezolid, as well as systemic antimycotics (fluconazole, am-photericin B), should be assessed.

1 In severe sepsis with PON or a critical condition of the patient, the greatest clinical effect is expected with the appointment of carbapenem (imipenem, meropenem, ertapenem), or cefepime with metronidazole, or new fluoroquinolones (levofloxacin, moxifloxacin).

2 If the risk of MRSA is high, the advisability of adding vancomycin or linezolid to any regimen should be discussed.

Sepsis with an established primary focus of infection

sepsis antibiotic therapy cephalosporin

The programs of empiric antibiotic therapy for sepsis do not differ significantly from the approaches to the treatment of infections of the localization where the primary focus of generalized infection is determined (Table 2). At the same time, in severe sepsis with PON, by adequate antibiotic therapy we mean the use of the most effective antibiotic already at the first stage of empirical therapy, given the extremely poor prognosis and the possibility of a rapid progression of the process to septic shock.

In the case of angiogenic (catheter) sepsis, the etiology of which is dominated by staphylococci, vancomycin and linezolid are the most reliable therapy regimens.

Table 4

Doses of intravenous antibiotics for empiric treatment of sepsis

Penicillins

Benzylpenicillin 1-2 million units 6 times a day

(streptococcal infections) Ampicillin 4 million units 6-8 times a day

(gas gangrene, meningitis)

Oxacillin 2 g 4-6 times a day

Generation I-III cephalosporins without antipseudomonal activity

Cefazolin 2 g 2-3 times a day

Cefotaxime 2 g 3-4 times a day1

Ceftriaxone 2 g once a day1

Cefuroxime 1.5 g 3 times a day

III-IV generation cephalosporins with antipseudomonal activity

Cefepime 2 g 2 times a day

Ceftazidime 2 g 3 times a day

Cefoperazone 2-3 g 3 times a day

Carbapenems
Imipenem 0.5 g 4 times a day or 1 g 3 times a day

Meropenem 0.5 g 4 times a day or 1 g 3 times a day

Ertapenem 1 g once a day

Combinations of p-lactams with inhibitorsb- lactamase

Amoxicillin / clavulanate 1.2 g 3-4 times a day

Ampicillin / sulbactam 1.5 g 3-4 times a day

Ticarcillin / clavulanate 3.2 g 3-4 times a day

Cefoperazone / sulbactam 4 g 2 times a day

Aminoglycosides

Amikacin 15 mg / kg per day 2

Gentamicin 5 mg / kg per day 2

Netilmicin 4-6 mg / kg per day 2

Fluoroquinolones

Levofloxacin 500-1000 mg once a day

Moxifloxacin 400 mg once a day

Ofloxacin 400 mg 2 times a day

Pefloxacin 400 mg 2 times a day

Ciprofloxacin 400-600 mg 2 times a day

Preparations with antistaphylococcal activity

Vancomycin 1 g 2 times a day

Linezolid 600 mg 2 times a day

Rifampicin 300-450 mg 2 times a day

Fusidic acid 500 mg 4 times a day

Preparations with anti-anaerobic activity

Clindamycin 600-900 mg 3 times a day

Lincomycin 600 mg 3 times a day

Metronidazole 500 mg 3-4 times a day

Antifungal drugs

Fluconazole 6-12 mg / kg / day - intravenous infusion at a rate not exceeding 10 ml / min

Amphotericin B 0.6-1.0 mg / kg / day - intravenous infusion in 400 ml of 5% glucose solution at a rate of 0.2-0.4 mg / kg / h

Amphotericin B liposomal 3 mg / kg 1 time per day

Caspofungin the first day - 70 mg once a day, then - 50 mg once a day

1 For CNS infections, the daily dose should be doubled

2 The daily dose can be administered in one or 2-3 administrations

Route of administration of antimicrobial agents

For sepsis, intravenous antibacterial agents are preferred. There is no convincing evidence in favor of intra-arterial or endolymphatic administration of antibiotics.

Combined use of antibacterial drugs

There is no convincing evidence for the routine administration of antibacterial drug combinations. The latest published meta-analysis shows that in sepsis, the combination of (3-lactams with aminoglycosides has no advantages over monotherapy (5-lactams in terms of both clinical efficacy and the development of resistance. The same clinical efficacy of monotherapy and combination therapy is shown for sepsis caused by Enterobacteriaceae and P. aeruginosa.

Duration of antibiotic therapy

Antibiotic therapy for sepsis is carried out until a stable positive dynamics of the patient's condition is achieved and the main symptoms of infection disappear. Due to the absence of pathognomonic signs of bacterial infection, it is difficult to establish absolute criteria for stopping antibiotic therapy. Usually, the question of stopping antibiotic therapy is decided individually based on a comprehensive assessment of the dynamics of the patient's condition. In general terms, the criteria for the adequacy of antibiotic therapy for sepsis can be presented as follows:

§ positive dynamics of the main symptoms of infection;

§ absence of signs of a systemic inflammatory reaction;

§ normalization of the function of the gastrointestinal tract;

§ normalization of the number of leukocytes in blood and leukocyte formula;

§ negative blood culture.

Persistence of only one sign of bacterial infection (fever or leukocytosis) is not absolute indication to continue antibiotic therapy. Isolated subfebrile fever (maximum daytime body temperature within 37.9 ° C) without chills and changes in peripheral blood can be a manifestation of post-infectious asthenia or non-bacterial inflammation after surgery and does not require continuation of antibiotic therapy, as well as persistence of moderate leukocytosis (9 - 12x10 ^ / l) in the absence of a shift to the left and other signs of bacterial infection.

The usual terms of antibiotic therapy for surgical infections of various localization (skin and soft tissues, peritonitis, NPVL) are from 5 to 10 days. Longer antibiotic therapy is not desirable due to the development possible complications treatment, the risk of selection of resistant strains and the development of superinfection. Recently published results of a controlled double-blind study showed the same clinical and bacteriological efficacy of 8- and 15-day NSVL therapy, with the risk of selection of resistant strains being higher with a longer course of treatment.

In the absence of a persistent clinical and laboratory response to adequate antibiotic therapy within 5-7 days, additional examination (ultrasound, computed tomography, etc.) is necessary to identify complications or an infection focus of another localization.

In certain clinical situations, longer regimens of antibiotic therapy are required. This is usually recommended for infections localized in organs and tissues in which therapeutic concentrations of antibiotics are difficult to achieve, therefore, there is a higher risk of persistence of pathogens and recurrence of infection. This applies primarily to osteomyelitis, infective endocarditis, secondary purulent meningitis. In addition, for S. aureus infections, longer courses of antibiotic therapy, 2 to 3 weeks, are usually also recommended. The developed recommendations for antibiotic therapy of sepsis are among the most typical and frequent in surgical practice community-acquired and nosocomial bacterial infections. However, some complex clinical situations are not considered in these guidelines, since they are difficult to standardize. In this case, the question of treatment tactics should be decided in conjunction with a specialist in antimicrobial chemotherapy.

Posted on Allbest.ru

...

Similar documents

Terminology and theories of the causes of sepsis, criteria for the classification of its types. Forms clinical course and diagnostic criteria for sepsis, surgical and general management. General provisions of antimicrobial therapy, criteria for its effectiveness.

presentation added on 05/11/2017


Risk factors for neonatal sepsis, types and methods of classification. Prevalence, etiology and predisposing factors of infection. Features of the clinical development of sepsis. Specific complications. Laboratory data, methods of treatment.

presentation added 02/14/2016


Basic hematological and biochemical parameters, as well as homeostasis parameters. Mathematical and statistical patterns of sepsis with different outcomes. Pathogenesis of sepsis and its influence on internal organs, methods of its diagnosis.

thesis, added 07/18/2014


The reasons for the constant or periodic entry into the bloodstream of microorganisms and their toxins from the local focus of infection. Mechanisms of obstetric sepsis. Diagnosis of severe sepsis and septic shock. Infusion therapy.

presentation added 01/25/2015


Familiarization with the criteria for the diagnosis of sepsis. Determination of causative agents of sepsis: bacteria, fungi, protozoa. Characteristics of the clinic of septic shock. Research and analysis of the features of infusion therapy. Study of the pathogenesis of septic shock.

presentation added on 11/12/2017


Characteristics of three periods of otogenic sepsis: conservative-therapeutic, surgical, prophylactic. Etiology, pathogenesis, clinical picture, symptoms of sepsis. Diagnostics and treatment of sepsis in a patient with chronic suppurative otitis media.

term paper, added 10/21/2014


Diagnostic criteria and signs of sepsis, stages of its development and the procedure for establishing an accurate diagnosis. Criteria for organ dysfunction in severe sepsis and its classification. Therapeutic and surgical treatment of sepsis, prevention of complications.

abstract, added 10/29/2009


The essence and factors contributing to the development of sepsis. The nature of the infectious agent. Modern classification and types of this pathological process, clinical picture and markers. Intensive care and the main antibiotics used in it.

presentation added on 05/13/2015


The concept and general characteristics of sepsis, its main causes and provoking factors of development. Classification and types, clinical picture, etiology and pathogenesis. Septic shock and its treatment. Symptoms and principles for diagnosing this disease.

presentation added 03/27/2014


The mechanism of development and micro-pathogens of sepsis - severe pathological condition, which is characterized by the same type of reaction of the body and the clinical picture. Basic principles of sepsis treatment. Nursing care for sepsis. Features of diagnostics.

The cause of sepsis	Dominant microbes	AB of the first line	Alternative AB
Intra-abdominal	Enterobacter, Enterococci, Anaerobes	IV imipinem 1 g 3 r / d or piperacillin	Antipseudomonal penicillins (ASPs): piperacillin IV, 3 g every 6 hours, carbecillin or azlocillin IV, 50 mg / kg every 4 hours)
Urosepsis (urinary tract)	Gr (¾) sticks, Enterobacter	Ciprofloxacin IV, 0.4 g 2 r / d	3rd generation cephalosporins (ceftriaxone, cefotaxin) or ASP with aminoglycosides (AMG) (gentamicin i.v. at 1.5 mg / kg after 8 hours or amikacin at 5 mg / kg after 8 hours)
Odontogenic	Streptococci, staphylococci, anaerobes of the oral cavity	Clindamycin IV, 0.6 g every 8 hours	Vancomycin (in a daily dose of 2 g) or 1st generation cephalosporins (cefazolin), unazine, amoxiclav with metronidazole

Table 11

End of work -

This topic belongs to the section:

Selected Lectures on Internal Medicine

On the site read: "selected lectures on internal medicine"

If you need additional material on this topic, or you did not find what you were looking for, we recommend using the search in our work base:

What will we do with the received material:

If this material turned out to be useful for you, you can save it to your page on social networks:

Tweet

All topics in this section:

Stages of diagnostic search for LNG
Stage 1 ¾ additional clinical and laboratory symptoms are revealed based on routine examination methods (OAC, OAM, LHC, radiography chest, ECG) and carefully collected

LNG (+) joint-muscle syndrome
Disease Clinical and laboratory symptoms Examination methods

LNG (+) skin lesions
Drug allergic reaction Drug rash: urticaria, mucosal ulceration, Quincke's edema, arthralgia, eosinophilia, drug-related relationship and disappearance of l

LNG (+) enlarged spleen
Sepsis (IE) Soft, enlarged spleen, tremendous chills, severe sweating and intoxication, hemorrhagic syndrome, anemia, changes in urine, may be present

Diagnostic search in patients with isolated LNG
The reasons for this LNG: sepsis, TJS, lymphogranulomatosis, IE, hypernephroma, DBST (SLE), cholangitis, leukemia, drug disease and artificial L. So, if the patient has a combination of LNG and repeated os

Arrhythmias of the heart
Cardiac arrhythmias are a change in the normal heart rate, regularity and source of exposure to the heart, as well as a disruption in the connection or sequence between activation of the atria and stomach

Rapid rhythm
Sinus tachycardia (ST) with a heart rate of more than 100 per minute (rarely more than 140 per minute). ST ¾ is not a rhythm disturbance, but a normal physiological response to increased sympathetic tone.

Arrhythmias as a disease syndrome
Pathology ST SB ES PZhT SPT TP MA A-B blockade II degree. OI

The effectiveness of various antiarrhythmics in rhythm disturbances
Drug ST Supraventricular ES Ventricular ES SPT PZhT Paroxysm MA Ia, novocaine

Obviously wrong rhythm
Extrasystole (ES) is the most frequent rhythm disturbance that a doctor has to deal with. This is a premature (early) contraction of a part or the whole heart

Cordaron, Rhythmilen, Aymalin, Etacizin are effective both for atrial ES and for ventricular ES
In case of ES and a tendency to tachycardia (heart rate over 100), it is better to administer: b-AB, cordarone or isoptin (2-4 ml of 0.25% solution, that is, 5-10 mg); In ES with bradycardia, rhythm is preferable

MA etiology
Organic heart diseases dominate (in 80% of cases) with the presence of hypoxia, hypercapnia, metabolic and hemodynamic disorders: rheumatic mitral heart disease and coronary artery disease with

Algorithm for stopping TP
Symptoms of acute cardiovascular failure (systolic blood pressure less than 90 mm Hg, CA, AL, fainting or angina attacks) ß ß no yes ß & szli

Bowel disease
Diseases of the intestines (small and large) develop in humans much more often than they are detected clinically. Chronic bowel diseases have always been and remain difficult to diagnose and

HCV treatment
Therapy for CVD, especially of severe forms, often presents significant difficulties, primarily due to the lack of etiotropic therapy (the etiology of CVD is unknown). BKr treatment is based on

Glomerulonephritis
The clinic of glomerulonephritis (synonym: nephritis), as an inflammatory lesion of the glomeruli, was described in detail in 1827 by the English physician Bright. Glomerulonephritis (GN) is a non-specific

The pathogenesis of opgn
An important feature of OPGN is the presence of a latent period between the manifestations of infection and the subsequent appearance of symptoms of nephritis. So, with infection of the pharynx, the latency period is 7-10

OPGN clinic
The number of cases of asymptomatic course of OPGN is 3-4 times higher than the number of cases of OPGN with obvious clinical symptoms. OPGN can occur in the form of endemic outbreaks or in the form of sporadic cases

Clinic HGN
CGN is characterized by a variety of symptoms and proceeds with periods of exacerbations and remissions. Often, CGN is detected only by random detection of abnormalities in urine tests or hypertension during different observational

Non-pharmacological therapy of CGN
Compliance with strict bed rest (for 2-4 weeks, sometimes up to 2-3 months), especially with hypertensive or mixed forms of chronic hepatitis. FN can increase renal ischemia, hematuria and proteinuria.

Chronic pyelonephritis and chronic renal failure
Chronic pyelonephritis (chronic tubulo-interstitial bacterial nephritis) is a nonspecific infectious and inflammatory process in the mucous membrane urinary tract (pelvis,

Clinic HP
A latent course (with a minimum number of symptoms) occurs in every fifth patient with CP. Most of these patients have no subjective symptoms: no complaints (and if the EU

Prognosis and outcomes of CP
CP accompanies a person all his life: it usually begins in childhood, then relapses of exacerbations occur, which eventually leads to chronic renal failure. In the elderly, the prognosis of CP is always serious due to atypical

The use of AB depending on the type of microbe
Microbe AB first line Reserve funds E. coli Ampicillin, amoxiclav, unazine, cephalosporins of the 1st and 2nd generation

CRF treatment
Secondary prevention of CRF is important, achieved by a rational diet, adequate treatment of kidney disease with correction of hypertension, kidney and urinary tract infections, and their obstruction (ICD, BPH). Treatment of chronic renal failure pato

List of abbreviations
AB ¾ antibiotics AB В atrioventricular hypertension ¾ arterial hypertension

36240 0

Sepsis is treated in an intensive care unit. It includes surgical treatment, antibiotic therapy, detoxification therapy and immunotherapy, elimination of water-electrolyte and protein disorders, restoration of impaired functions of organs and systems, balanced high-calorie nutrition, symptomatic treatment.

An integrated approach to the treatment of sepsis involves not only a combination of means and methods, but also their parallel, simultaneous use. Multifactorial changes in the body with sepsis, the characteristics of the primary focus of infection, the initial state of the body, concomitant diseases determine an individual approach to the treatment of a patient with sepsis.

Surgery

Pathogenetic and etiotropic therapy for sepsis involves the elimination of the source of infection and the use of antibacterial drugs.

Surgical intervention is performed on an emergency or urgent basis. After the stabilization of the basic functions of the body, primarily hemodynamics. Intensive therapy in these cases should be short-term and effective, and the operation is performed as quickly as possible with adequate pain relief.

Surgical intervention can be primary when it is performed with the threat of generalization of the infection or with sepsis, which complicated the course of purulent diseases. Repeated surgical interventions are performed when sepsis develops into postoperative period or primary surgery did not improve the sepsis patient.

During surgery, the source of infection is removed, if the state of the focus permits with a limited purulent process (breast abscess, post-injection abscess), or an organ with an abscess (pyosalpinx, purulent endometritis, spleen abscess, kidney carbuncle). More often, surgical treatment consists in opening an abscess, phlegmon, removing non-viable tissues, opening purulent streaks, pockets, and drainage.

With purulent peritonitis, the task of surgical treatment is to eliminate the cause, adequate sanitation of the abdominal cavity (if indicated, repeated sanitization); with osteomyelitis - opening of intraosseous abscesses and drainage.

Repeated surgical interventions are performed not only with the development of complications in the postoperative period, the appearance of purulent metastases, and suppuration of wounds. Operations include opening and draining purulent streaks, pockets, changing drainages, overdraining purulent foci, cavities, repeated necrectomy, secondary surgical treatment of purulent wounds, opening and draining metastatic purulent foci.

Sanitation of purulent foci by closed methods (puncture, drainage) is performed with formed abscesses. These are intra-abdominal and intrahepatic abscesses, suppurating pancreatic cysts, non-draining lung abscesses, pleural empyema, purulent arthritis.

Infected implants, foreign bodies that caused the generalization of the infection, must be removed (metal structures during osteosynthesis, vascular and joint prostheses, heart valves, mesh implants for plastic surgery of abdominal and chest wall defects). Infected venous catheters must also be removed.

Antibacterial therapy

The importance of etiotropic therapy for sepsis is undeniable, it is started as early as possible. The fight against microflora is carried out as in the focus of infection - local antibacterial therapy - adequate drainage, staged necrectomies, flow-washing drainage, the use of antiseptics: sodium hypochlorite, chlorhexidine, dioxidine, ultrasonic cavitation, etc.

Antibiotics are the basis of general antibiotic therapy. Antibiotic therapy can be in two versions - the primary choice of drugs or a change in the antibiotic therapy regimen. Most often, with sepsis, antibiotic therapy is empirical: drugs are chosen taking into account the alleged pathogen and depending on the primary source. For example, wound sepsis most often has a staphylococcal nature, abdominal sepsis is mixed, mainly gram-negative, including anaerobic.

The high risk of serious complications and death, when a delay in effective antibiotic therapy, even for a day, is fraught with unpredictable consequences, makes treatment begin with combination therapy, and in severe sepsis, with reserve antibiotics.

The drugs of choice for the empiric treatment of severe sepsis are third-fourth generation cephalosporins, fluoroquinolones in combination with clindomycin or dioxidine or metrojil, and carbopenems for monotherapy.

IN modern conditions the role of nosocomial infection in the development of sepsis is extremely high, and with the development of multiple organ failure (MOF), the choice of an antibiotic for empiric therapy is important, if not decisive. Under such conditions, carbopenems (imipenem, meropenem) play a primary role.

The advantage of these drugs is a wide spectrum of action on the aerobic and anaerobic flora (the drug is used in a monovariant). Microflora is highly sensitive to antibiotics of this group. The drugs are characterized by high tropism for different tissues, and the tropism for the peritoneum is higher than that of all other antibiotics.

In choosing an antibiotic for empiric therapy, it is important to establish not only the presumptive causative agent of the infection, but also the primary source (skin and subcutaneous tissue, bones and joints, pancreas, peritonitis with colon perforation or appendicitis). The selection of antibiotics, taking into account their organotropy, is one of the most important components of rational antibiotic therapy. The organotoxicity of drugs is also taken into account, especially in the conditions of MOF.

When carrying out antibiotic therapy, one should take into account the possibility of massive release of bacterial endotoxins during the bactericidal action of drugs. When the shell of gram-negative bacteria is destroyed, a polysaccharide (endotoxin) is released, gram-positive bacteria - teichoic acid with the development of Yarish-Herxheimer's syndrome. The toxic effect of these substances on the cardiovascular system is especially pronounced.

After isolating the pathogen from the focus and blood, antibiotic therapy is adjusted.

For staphylococcal sepsis caused by methicillin-sensitive staphylococcus, oxacillin is used, for intraosseous foci of infection - in combination with gentamicin.

If sepsis is caused by methicillin-resistant strains of staphylococcus, vancomycin or rifampicin is indicated. The latter is rapidly developing resistance of microflora, which determines the need to combine it with ciprofloxacin.

In streptococcal sepsis, the antibiotics of choice, taking into account the sensitivity of the microbial flora, are ampicillin, cefotoxin, vancomycin, imipenem, meropenem.

Pneumococcal sepsis determines the use of third-fourth generation cephalosporins, carbopenems, vancomycin.

Among the gram-negative flora, enterobacteriaceae, multi-resistant to antibiotics, predominate: E. coli, P. mirabien, P. vulgaris, Klebs.spp., Citrobacterfreundis. The main antibiotics in the treatment of diseases caused by these microorganisms are carbopenems. When isolating Pseudomonas spp., Acinetobacter spp., Which are usually multidrug-resistant, carbopenems or ceftazidine in combination with amikacin are the antibiotics of choice.

Abdominal sepsis caused by anaerobic pathogens (bacteroids) or wound clostridial sepsis determine the need for combination therapy (cephalosporins, fluoroquinolones in combination with clindamycin, dioxidine, metronidazole), and with abdominal sepsis, carbopenems.

With fungal (candidal) sepsis, antibiotic therapy includes caspofungin, amphotericin B, fluconazole.

The basic principles of antibiotic therapy for sepsis are as follows.

Empiric therapy begins with the use of the maximum therapeutic doses of third-fourth generation cephalosporins, semi-synthetic aminoglycosides; if ineffective, they quickly switch to fluoroquinolones or carbopenems. Correction of antibiotic therapy is carried out according to the results of bacteriological studies of the contents of a purulent focus, blood. If the drugs are effective, treatment is continued.

If necessary, a combination of two antibiotics with a different spectrum of action or an antibiotic with one of the chemical antiseptics (nitrofurans, dioxidine, metronidazole) is used.

Antibacterial drugs are administered in a variety of ways. Antiseptics are used locally (intrapleurally, endotracheally, intraosseously into the joint cavity, etc., depending on the localization of the focus), and antibiotics are administered intramuscularly, intravenously, intraarterially.

The duration of the course of antibiotic therapy is individual and depends on the patient's condition (treatment is continued until the signs of SSVR are eliminated: body temperature normalizes or decreases to subfebrile numbers, the number of leukocytes is normalized or moderate leukocytosis with a normal blood count).

With osteomyelitis, the remaining cavity in the liver, lung after sanitation of an abscess, residual pleural cavity with empyema, with sepsis caused by S. aureus, antibiotic therapy is continued for 1-2 weeks after clinical recovery and two negative blood cultures.

The response to adequate antibiotic therapy appears within 4-6 days. The lack of effect determines the search for complications - the formation of metastatic foci, purulent streaks, the appearance of foci of necrosis.

Hypovolemia with shock, especially infectious-toxic, is always present and it is determined not only by fluid loss, but also by its redistribution in the body (intravascular, interstitial, intracellular). Violations of the BCC are caused both by the developed sepsis and by the initial level of changes in the water-electrolyte balance associated with the underlying disease (abscess, phlegmon, pleural empyema, festering wound, burns, peritonitis, osteomyelitis, etc.).

The desire to restore the BCC to normovolemia is due to the need to stabilize hemodynamics, microcirculation, oncotic and osmotic blood pressure, and normalize all three water basins.

Restoring the water-electrolyte balance is a matter of paramount importance and is provided with colloidal and crystalloid solutions. From colloidal solutions, preference is given to dextrans and hydroxyethylated starch. For the restoration of the oncotic properties of blood, correction of hypoalbuminemia (hypoproteinemia) in an acute situation, albumin in concentrated solutions, native, freshly frozen donor plasma remain ideal means.

To correct violations of the acid-base state, a 1% solution of potassium chloride for alkalosis or a 5% solution of sodium bicarbonate for acidosis is used. To restore the protein balance, amino acid mixtures (aminone, aminosol, alvezin), protein, albumin, dry and native plasma of donor blood are injected. To combat anemia, regular transfusions of freshly preserved blood, erythrocyte mass are shown. Minimum concentration hemoglobin in sepsis 80-90 g / l.

Detoxification therapy

Detoxification therapy is carried out according to general principles, it includes the use of infusion media, saline solutions, as well as forced diuresis. The amount of injected liquid (polyionic solutions, 5% glucose solution, polyglucin) is 50-60 ml (kg / day) with the addition of 400 ml of hemodesis. About 3 liters of urine should be released per day. To enhance urination, use lasix, mannitol. With multiple organ failure with a predominance renal failure use methods of extracorporeal detoxification: plasmapheresis, hemofiltration, hemosorption.

In acute and chronic renal failure, hemodialysis is used, which allows you to remove only excess fluid and toxic substances of low molecular weight. Hemofiltration expands the range of toxic substances removed - products of impaired metabolism, inflammation, tissue decay, bacterial toxins. Plasmapheresis is effective for removing toxic substances dissolved in plasma, microorganisms, and toxins. The removed plasma is replenished with donor fresh frozen plasma, albumin in combination with colloidal and crystalloid solutions.

In severe sepsis, the level of IgY, IgM, IgA especially decreases. A pronounced decrease in T- and B-lymphocytes reflects the progressive insufficiency of immunity, when the infection process does not resolve. Indicators of violation (perversion) of the body's immune response are manifested by an increase in the level of CEC in the blood. A high level of CEC also indicates a violation of phagocytosis.

Of the means of specific exposure, the use of antistaphylococcal and anticolibacillary plasma, antistaphylococcal gamma globulin, polyglobulin, gabriglobin, sandobulin, pentaglobin is shown. With the suppression of cellular immunity (a decrease in the absolute content of T-lymphocytes), violation of the phagocytic reaction, transfusion of leukocyte mass, including from immunized donors, freshly prepared blood, the appointment of thymus preparations - thymalin, taktivin are shown.

Passive immunization (substitution therapy) is carried out during the period of development, at the height of the disease, while during the period of recovery, active immunization means are shown - toxoid, autovaccines. Non-specific immunotherapy includes lysozyme, prodigiosan, thymalin. Taking into account the role of cytokines in the development of sepsis, interleukin-2 (roncoleukin) is used with a sharp decrease in the level of T-lymphocytes.

Corticosteroids are indicated as replacement therapy after determining hormonal levels. Only when sepsis is complicated by bacterial toxic shock, prednisolone is prescribed (on the 1st day up to 500-800 mg, then 150-250 mg / day) for a short period (2-3 days). Corticosteroids in usual therapeutic doses (100-200 mg / day) are used when allergic reactions occur.

because of high level kininogens in sepsis and the role of kinins in microcirculation disorders in the complex therapy of sepsis include proteolysis inhibitors (gordox 200,000 - 300,000 U / day or counterkal 40,000 - 60,000 U / day).

Symptomatic treatment involves the use of cardiac, vascular drugs, analgesics, anticoagulants, drugs that reduce vascular permeability, etc.

Intensive therapy for sepsis is carried out for a long time, until a steady improvement in the patient's condition and restoration of homeostasis.

The diet of patients with sepsis should be varied and balanced, high in calories, with sufficient protein and vitamins. Be sure to include fresh vegetables and fruits in the daily diet. In normal gastrointestinal tract activity, preference should be given to enteral nutrition, otherwise complete or complementary parenteral nutrition is required.

A high degree of catabolic processes in sepsis is determined by SNP and is accompanied by the consumption of tissue protein as a result of the destruction of its own cellular structures.

The specific energy value of the daily ration should be 30-40 kcal / kg, protein intake 1.3-2.0-1 kg or 0.25-0.35 g nitrogen / kg, fat - 0.5-1 g / kg. Vitamins, trace elements and electrolytes - in the amount of daily requirements.

A balanced diet is started as early as possible, without waiting for catabolic changes in the body.

For enteral feeding, ordinary food products are used; for tube feeding, balanced nutritional mixtures are provided with the addition of certain ingredients. Parenteral nutrition is provided with glucose solutions, amino acids, fat emulsions, electrolyte solutions. You can combine tube and parenteral nutrition, enteral and parenteral nutrition.

Specific types of sepsis

Sepsis can develop when some specific pathogens enter the bloodstream, for example, with actinomycosis, tuberculosis, etc.

Actinomycotic sepsis complicates visceral actinomycosis. Dissemination in actinomycosis can lead to an isolated lesion of one organ by metastasis or to the development of metastases in several organs simultaneously.

Clinically, actinomycotic pyemia is accompanied by a significant exacerbation of the actinomycotic process, an increase in temperature to 38-39 ° C, the formation of new actinomycotic infiltrates, purulent foci in different areas body and organs, severe pain, exhaustion and severe general condition of the patient.

For the treatment of actinomycotic sepsis, in addition to the means and methods used for bacterial sepsis, special large doses of antibiotics, actinolysates and blood transfusion are important.
Anaerobic sepsis can develop with anaerobic gangrene caused by Clostridia. Sepsis can also be caused by other anaerobic microorganisms, although this is much less common.

Anaerobic sepsis usually develops in severe wounds, in weakened, exsanguinated wounded. There is a rapid development of anaerobic gangrene with a high body temperature (40-40.5 ° C), frequent and low pulse, extremely serious condition, confusion or loss of consciousness (sometimes it is preserved, but excitement, euphoria is noted). In peacetime conditions, anaerobic sepsis almost never occurs.

Intramuscular and intravenous drip of large doses of antigangrenous serum (10-20 prophylactic doses per day), intravenous drip and intramuscular administration of a mixture of antigangrenous phages should be added to the above method of treating sepsis in anaerobic form.

Sepsis of newborns is more often associated with the introduction of infection (mainly staphylococcus) through the umbilical wound, abrasions, etc. Jumping temperature, lethargy, skin rash, jaundice, diarrhea and vomiting, hemorrhages in the skin and mucous membranes make up the clinical picture of sepsis in children. Chills are rare, and the spleen enlarges early.

Pneumonic foci, purulent pleurisy, lung abscesses and pericarditis, which occur in sepsis and are taken for the underlying disease, lead to diagnostic errors. Sometimes sepsis occurs under the guise of food intoxication.

VC. Gostishchev

Microbiological diagnosis of sepsis.

Based on microbiological (bacteriological) examination of peripheral blood and material from the alleged focus of infection. When isolating typical pathogens (Staphylococcus aureus, Klebsiella pneumoniae, Pseudomonas aeruginosa, fungi), one positive result is sufficient for the diagnosis; if MBs are isolated that are skin saprophytes and can contaminate the sample (Staphylococcus epidermidis, other coagulase-negative staphylococci, diphtheroids), two positive blood cultures are required to confirm true bacteremia.

The diagnosis of sepsis should be considered proven if the same microorganism is released from the alleged focus of infection and from the peripheral blood and there are signs of SIRS. If a microorganism is secreted from the blood, but there are no signs of SIRS, the bacteremia is transient and sepsis is not.

Basic requirements for microbiological blood tests:

1. Blood for research must be taken before the appointment of AB; if the patient is already receiving ABT, blood should be collected immediately before the next administration of the drug

2. The standard of blood tests for sterility - sampling of material from two peripheral veins with an interval of up to 30 minutes, while blood must be drawn from each vein into two vials (with media for the isolation of aerobes and anaerobes); if there is suspicion of a fungal etiology, it is necessary to use special media for the isolation of fungi.

3. Blood for research must be taken from a peripheral vein. Blood sampling from the catheter is not allowed (except in cases of suspected catheter-associated sepsis).

4. Blood sampling from the peripheral vein should be carried out with careful observance of asepsis: the skin at the venipuncture site is treated twice with a solution of iodine or povidone-iodine with concentric movements from the center to the periphery for at least 1 min, immediately before the collection the skin is treated with 70% alcohol. During venipuncture, the operator uses sterile gloves and a sterile dry syringe. Each sample (about 10 ml of blood or in the volume recommended by the manufacturer's instructions for the vials) is taken into a separate syringe. The cap of each vial with the medium is treated with alcohol before piercing with a needle to inoculate blood from a syringe.

NB! Absence of bacteremia does not rule out sepsissince Even with the most scrupulous adherence to the technique of blood sampling and the use of modern microbiological technologies in the most severe patients, the frequency of detection of bacteremia does not exceed 45%.

To make a diagnosis of sepsis, you should also conduct the necessary laboratory and instrumental studies to assess the state of a number of organs and systems (according to the classification of sepsis - see question 223), assess the overall severity of the patient's condition according to the A.Baue, SOFA, APACHE II, SAPS-II scales.

Basic principles of sepsis therapy:

1. Complete surgical debridement of the site of infection - without eliminating the focus of infection, intensive measures do not lead to a significant improvement in the patient's condition; if a source of infection is found, it should be drained as much as possible, according to indications, perform necrectomy, remove internal sources of contamination, eliminate perforations of hollow organs, etc.

2. Rational antibiotic therapy - can be empirical and etiotropic; in the case of an unidentified focus of infection, AB should be used with the widest possible spectrum of action.

Principles of antibiotic therapy:

ABT for sepsis should be prescribed urgently after the nosological diagnosis has been clarified and before the results of bacteriological research are obtained (empirical therapy); after receiving the results of bacteriological research, the ABT mode can be changed taking into account the isolated microflora and its antibiotic sensitivity (etiotropic therapy)

At the stage of empirical ABT it is necessary to use AB with a wide spectrum of activity, and, if necessary, combine them; the choice of a specific empirical ABT is based on:

a) the spectrum of the alleged pathogens, depending on the localization of the primary focus

b) the level of resistance of nosocomial pathogens according to microbiological monitoring data

c) conditions for the occurrence of sepsis - community-acquired or nosocomial

d) the severity of infection, assessed by the presence of multiple organ failure or the APACHE II scale

For community-acquired sepsis, drugs of choice are III generation cephalosporins (cefotaxime, ceftriaxone) or IV generation fluoroquinolones (levofloxacin, moxifloxacin) + metronidazole, for nosocomial sepsis, drugs of choice are carbapenems (imipenem, meropenem) + vanesolidcomycin or linezolidycin or

When an etiologically significant microorganism is isolated from the blood or primary focus of infection, it is necessary to carry out etiotropic ABT (methicillin-susceptible staphylococcus - oxacillin or oxacillin + gentamicin, methicillin-resistant staphylococcus - vancomycin and / or linezolid, pneumococcus - vancomycin and / or linezolid, pneumococcus - cephalosporin III; etc., anaerobes - metronidazole or lincosamides: clindamycin, lincomycin, candida - amphotericin B, fluconazole, caspofungin)

ABT of sepsis is carried out until a stable positive dynamics of the patient's condition is achieved, the main symptoms of infection disappear, and negative blood culture

3. Pathogenetic therapy of complicated sepsis:

a) hemodynamic support:

Hemodynamic monitoring is carried out invasively using a floating Swan-Ganz catheter, which is inserted into pulmonary artery and allows you to fully assess the state of blood circulation at the patient's bed

Infusion therapy with crystalloid and colloid solutions in order to restore tissue perfusion and normalize cell metabolism, correct hemostasis disorders, reduce septic cascade mediators and the level of toxic metabolites in the blood

Within the next 6 hours, it is necessary to achieve the following target values: CVP 8-12 mm Hg, ABP\u003e 65 mm Hg, urine output 0.5 ml / kg / h, hematocrit\u003e 30%, blood saturation in the superior vena cava 70%.

The volume of infusion therapy is selected strictly individually, taking into account the patient's condition. It is recommended in the first 30 minutes of infusion therapy to introduce 500-1000 ml of crystalloids (physical solution, Ringer's solution, Normosol solution, etc.) or 300-500 ml of colloids (Destran, albumin, gelatinol solutions , hydroxyethyl starches), evaluate the results (in terms of increased blood pressure and cardiac output) and tolerance of the infusion, and then repeat the infusion in an individual volume.

The introduction of drugs that correct the state of the blood: infusion of cryoplasma with coagulopathy of consumption, transfusion of donor erythrocyte mass with a decrease in hemoglobin levels below 90-100 g / l

Application according to indications of vasopressors and agents with a positive inotropic effect - indicated if the corresponding fluid load is not able to restore adequate blood pressure and organ perfusion, which should be controlled not only by the level of systemic pressure, but also by the presence in the blood of anaerobic metabolic products such as lactate, etc. .d. Drugs of choice for correcting hypotension in septic shock - norepinephrine and dopamine / dopamine 5-10 mcg / kg / min via a central catheter, first-line drug to increase cardiac output - dobutamine 15-20 mcg / kg / min IV

b) correction of acute respiratory failure (ARDS): respiratory support (ALV) with parameters that ensure adequate ventilation of the lungs (PaO 2\u003e 60 mm Hg, PvO 2 35-45 mm Hg, SaO 2\u003e 93%, SvO 2\u003e 55%)

c) adequate nutritional support - necessary, because PON in sepsis is accompanied by hypermetabolism, in which the body covers its energy costs by digesting its own cellular structures, which leads to endotoxicosis and potentiates multiple organ failure.

The earlier nutritional support is started, the better results, the way of nutrition is determined by the functional ability of the gastrointestinal tract and the degree of nutritional deficiency.

Energy value - 25 - 35 kcal / kg / day in the acute phase and 35 - 50 kcal / kg / day in the phase of stable hypermetabolism

Glucose< 6 г/кг/сут, липиды 0,5 - 1 г/кг/сут, белки 1,2 – 2,0 г/кг/сут

Vitamins - standard daily intake + vitamin K (10 mg / day) + vit B1 and B6 (100 mg / day) + vit A, C, E

Trace elements - standard daily set + Zn (15-20 mg / day + 10 mg / l in the presence of loose stools)

Electrolytes - Na +, K +, Ca2 + according to balance calculations and plasma concentration

d) hydrocortisone in small doses 240-300 mg / day for 5-7 days - accelerates the stabilization of hemodynamics and allows you to quickly cancel vascular support, indicated in the presence of signs of septic shock or adrenal insufficiency

e) anticoagulant therapy: activated protein C / zigris / drotrecogin-alpha - an indirect anticoagulant, also has anti-inflammatory, antiplatelet and profibrinolytic effects; the use of activated protein C at a dose of 24 μg / kg / hour in the first 96 hours of sepsis reduces the risk of death by about 20%

f) immunotherapy: pentaglobin (IgG + IgM) at a dose of 3-5 ml / kg / day for 3 days - limits the damaging effect of pro-inflammatory cytokines, increases the clearance of endotoxins, eliminates anergy, enhances the effects of beta-lactams. Intravenous administration of immunoglobulins is the only really proven method of immunocorrection for sepsis, which increases survival.

g) prevention of deep vein thrombosis in long-term patients: heparin 5000 IU 2-3 times / day n / a 7-10 days under mandatory control of aPTT or low molecular weight heparins

h) prevention of gastrointestinal stress ulcers: famotidine / kvamatel 50 mg 3-4 times / day IV, omeprazole 20 mg 2 times / day IV

i) extracorporeal detoxification (hemodialysis, hemofiltration, plasmapheresis)