A method for preventing sepsis in children after surgery

 

(57) Abstract:

The invention relates to medicine, namely to surgery and immunology, and can be used, in particular, to prevent septic complications after radical surgery in children with congenital heart defects. To do this for 3-4 days before surgery and one day after the operation, determine the content of the CD 95 in the blood and when it is above 4.0% carried out the in vitro immunomodulation immunostimulating effect on the auto leukocytes of the patient. The method provides a reduction in the number of postoperative septic complications due to effective immune. 1 C.p. f-crystals.

The invention relates to medicine, namely to surgery, and can be used to prevent septic complications after radical surgery in children with congenital heart defects (CHD).

Intracardiac and wound infections remain one of the most difficult diagnostic and therapeutic problems of modern surgery. After operations in the extracorporeal circulation (EC) purulent-septic complications occur in 5-10 times more often than other operations on heart (Shevchenko Y. L. , Khubulava gg , 1996; Kostyuchenko A. the 1987), and according to our center - of 3-3 .5%. Domestic and foreign studies on the pathogenesis of sepsis suggest that the severity of the current define three leading syndrome of endogenous intoxication, multiple organ failure and acquired immunodeficiency syndrome (Beloborodov Century B. , 1997; Makarova N. P., Konichiwa I. N., 1995). If the first two syndromes occur when deployed clinic sepsis, a syndrome of immune deficiency is formed already in the early stages and often precedes the development of infection. In this regard, timely immunotherapy is considered as a necessary component of comprehensive treatment of surgical patients. The study of specific immunity preoperative and early postoperative period in patients operated in the IR condition, has a practical value, as it allows through rational immune to prevent septic complications.

Known methods of prevention and treatment of postoperative complications. For example, the patent of the Russian Federation N2099060 (1997), according to which twice for 48 and 24 hours prior to surgery intramuscularly injected pyrogenes, tocopherol and pyridoxine. The patent of the Russian Federation N2144367 (2000) in pre - and postoperative period profile include bioperin, which is administered orally. A common disadvantage of the above methods is the absence of selective perfusion effects on the immune system and a differentiated approach to patients.

In the literature there is evidence of high clinical efficacy of extracorporeal immune (EIK) in the treatment of patients with advanced purulent-destructive diseases, including after abdominal surgery (Fingers A. C. et al. Cytokines in the treatment of generalized surgical infection.// Anest. and reanim.- 2000. -N2. - S. 61-66). A common shortcoming of these methods is that the treatment is carried out in the anabolic phase of sepsis in the phase of wound depletion, i.e., in the midst of disease; when the purpose of therapy is not investigated the immune status of patients; there is no individual approach.

The prototype of the invention, the selected method for the prevention and treatment of sepsis in burn patients (patent RF N 2123341, 1998). The essence of the prototype method is that leukocytes tyazhelogruzhennogo processed drug thymic immunogenum outside the body. To do this, produce a blood from a vein of the patient in the number 400-500 ml. Bottle of heparinisation the Ute leukocyte film and diluted with 0.9% NaCl 200-250 ml medium 199 200 to 250 ml. The red blood cells returned to the patient. In the vial is injected immunofan 75-125 mcg 1109leukocytes. The resulting solution is incubated for 90 min at 37oC, then centrifuged 15 min with a speed of 2000 rpm vial of solution to remove leukocyte film, further leukocytes washed 3 times with sterile 0.9% NaCl 390-485 ml Washed leukocytes diluted NaCl 0,9% 50-100 ml of intravenous drip infusion of the patient.

The disadvantages of this method include:

1. The absence of a differentiated approach to the appointment of EIK. Total in vitro immune correction is possible only if tyazheloobozhzhennykh patients who have a marked deficiency of cellular immunity and nonspecific factors of protection throughout the disease, in addition, 75% of burn patients revealed a high titer of antibodies to infectious agents (Spins M., et al., 1998). Given the invasiveness and high cost EIK, this approach makes it impractical, and in some cases impossible to use in other indications.

2. The inability of the method used for the treatment of children with hematological patients and patients with low circulating blood volume (CBV), because b is before a lot of stages, each of which requires careful sterility (numerous ukoli in containers with sterile environments, the selection of plasma, red blood cells etc). In addition, a five-fold centrifugation in the process of obtaining lacokanostra traumatic to blood cells. The time from blood sampling before reinfused of erythromyci is not less than 1 hour, and reinfused lakomski - 4-5 hours.

4. The low efficiency of the method in connection with the impossibility of allocating highly concentrated lakomski and, as a consequence, reinfuse insufficient number of leukocytes (according to this method, the total number of leukocytes enriched immune stimulator, not more 0,8109; the presence lacokanostra other blood cells (erythrocytes, platelets).

These drawbacks are eliminated in the invention.

The task of the invention is to increase the efficiency of the method through a differentiated approach to the preoperative preparation of the patient. The technical result achieved by the invention: an individual approach to the appointment EIK, reducing the number of postoperative septic complications, and a shorter hospital stay. The problem is solved in that the rovi above 4.0% spend EIK using, for example, immunofan or polyoxidonium, or any other immunostimulant.

Our studies revealed that a high degree of readiness of cells to apoptosis is closely correlated with the percentage of occurrence of septic complications after surgery. Resting Mature lymphocytes apoptosis is not affected. However, they become sensitive to induction of apoptosis after activation: this mechanism is destroyed a significant portion of the lymphocytes in the deployment of the immune response. Specialized receptor signals to the induction of apoptosis is a membrane molecule Fas (CD 95, mol. mass 48000). It is known that cytokines or their analogues can induce Fas-dependent apoptosis (Yarylo A. A., 1999). This gave us reason to assume the relationship of the magnitude of CD 95 with the incidence of septic complications in children after surgery. The monitoring of immunological parameters as before the surgery (3-4 days), and in the early postoperative period (the next day), showed the presence 81% of this group of children of secondary immunodeficiency. A radical operation in respect of CHD in children and early postoperative period include a number of immunosuppressive factors: operating t the/P> As a result of researches it is established that the value of CD 95 above 4.0% postoperative period in 99% of cases was complicated by sepsis.

Holding EIK children with the value of CD 95, greater than 4,0% (regardless of the value registered before surgery or in the early postoperative period), helped to avoid septic complications. In these patients was observed normalization of indices of immunity in combination with satisfactory clinical performance. This is because reinfuse autologous cells with restored properties becomes a triggering factor in the subsequent reintegration of the various elements of the immune system. As immunostimulant we used immunofan, the regulatory effect of which is characterized by the ability to restore the immune and redox systems of the body, and polyoxidonium with a wide range of immunomodulating actions.

With this purpose, and may use any other immunostimulant, suitable for parenteral administration.

The operability of the invention the following examples.

Example 1.

ing heart disease, atrial septal defect, circulatory insufficiency II And pulmonary hypertension grade II (34 mm RT.cent.), DN-1 degree.

During laboratory tests conducted for 4 days before surgery, found: lymphopenia (18%), moderate leukopenia (5,0109/l). Blood cultures sterile. The content of CD 95 blood was 5.2%. The determination was performed by the method of flow cytofluorometry device company "Coulter XL using monoclonal antibodies manufactured by the Institute of immunology MZ the Russian Federation.

For the prevention of septic complications for 3 days before surgery, the patient was held EIK on fractionator blood MCs3p company HAEMONETICS (USA) using PBSC (Peripheral Blood Stem Cell).

As an anticoagulant used ACD-A (BAXTER) in a ratio of 1: 12. The number of recirculation cycles was equal to 4 and provided optimum final harvesting of stem cells and their total volume. The collected volume of the recirculated erythrocytes was 40 ml was Used bell of Latham low volume (125 ml). During programmable leukocytapheresis used mode leaching of platelets from lectropol. The rate of return of blood to the patient during the procedure entrata revealed the following: at the absolute prevalence of nuclear cells relative content of mononuclear cells number was 98,3%. The auto leukocytes were incubated with polyoxidonium in the highest dose (12 mg) at 25oC for 25 minutes. Lacokanostra enriched 2 ml of 1% ATP, which in vitro "download" phagosome neutrophils. Immediately after the incubation time has been reinfusion. The total number of returned leukocytes was 7,8109. The time from the start of blood sampling to reinfused leukocytes 3 hours.

The day before surgery, the blood is taken for analysis. Lymphocytes or 37.4%, number of leukocytes 8,9109/l, the content of CD 95 amounted to 2.1%.

The radical correction of the defect in the conditions of artificial blood circulation. Cold cardioplegia. Closure of atrial septal defect. Time IR 1 hour and 40 minutes. The time of clamping of the aorta 60 minutes. The correction of the defect adequate. During the first two days after surgery was carried out on artificial lung ventilation, inotropic support and prophylactic antibiotic therapy. A day after the operation, blood is taken for analysis. The content of CD 95 was 3.2%. In this regard, EIK was not conducted.

As a result of treatment has been a rapid improvement. On the 16th day after surgery, the wound healed by first intention. Blood is an in satisfactory condition at the place of residence. Visual inspection of 1.5 months - satisfactory condition, complaints almost does not show. Indicators of immunological indexes on subnormal level.

Example 2.

Patient A., age 9, was admitted to the Department of surgery for surgical intervention with a diagnosis of congenital heart disease, persistent ductus arteriosus, circulatory failure - 0, pulmonary artery pressure of 25 mm RT. Art. , DN - 0. For 3 days before surgery the study of blood. Complete blood count and biochemical parameters - no pathological changes. Blood cultures sterile. Figure 95 CD is 4.0%. In this regard, the EIT program of preoperative preparation were not included.

The child had a radical correction of the defect: left anterolateral thoracotomy, revision of aortic closure of patent ductus arteriosus. One day after surgery taken blood for research. Figure 95 CD was equal to 4.6%. For the prevention of septic complications the child was made EIK with immunogenum (1 ml of 0.005% solution) by the method described above. The patient demonstrated a positive trend in the postoperative period. 26 the day the patient was discharged at the place of residence in the Aries. Control examination after 2 months - condition is satisfactory, no complaints.

Example 3.

Patient g was Admitted to the Department of surgery for surgical intervention with a diagnosis of congenital heart disease, a large atrial septal defect, circulatory failure, I grade pulmonary hypertension of I degree (26 mm RT.cent.), DN - 0. For 4 days before surgery taken blood for research. Complete blood count and biochemical parameters without pathological changes. Blood cultures sterile. Figure 95 CD equal to 2.2%. In this regard, the program preoperative preparation of the patient was not included EIK.

The radical correction of the defect in terms of IR. Cold cardioplegia. Plastic defect a felt patch. Time IR 66 minutes. The time of clamping of the aorta 48 minutes. Blood loss of 200 ml of correction of the defect adequate. Prophylactic antibiotic therapy.

One day after surgery taken blood for research. Figure 95 CD was equal to 2.9%, and in the course of post-operative therapy was not included conducting EIK.

The postoperative period was uneventful, the wound healed by first intention. At 18 days after surgery in trolly inspection in a month the condition is satisfactory, no complaints. Indicators of immunological indexes and leukogram at a subnormal level.

Under our observation were 42 children aged 7 to 14 years of age with congenital heart defects submitted to the Department of surgery for radical surgery.

In all 42 cases children for 3-4 days before surgery and one day after surgery was determined by the content of CD 95 in the blood. If the value of this index is higher than the 4.0 percent held a session EIK using immunofan, polyoxidonium, RIL-2, etc.

While 25 patients was conducted session EIK before surgery, 17 after surgery, 12 patients before and after surgery, 9 patients EIK was not conducted. Determination of the 95 CD in the blood of the child gives the chance to carry out EIK when it is necessary, and thus in some cases not to apply traumatic and costly procedure. This preventive approach made it possible to avoid the occurrence of sepsis in the postoperative period in 98.6% of cases. It should be noted that differentiated immunotherapy reduced the treatment time compared to conventional.

Thus, the inventive method is the most effective. is Yunosti due to the selection of high purity and high concentration of lakomski; the possibility of using the method for the treatment of children in any surgical interventions; reduction in the number of postoperative septic complications; shorter hospital stay.

The method is tested on the volume of clinical material and can be widely used in clinical practice.

1. A method for preventing sepsis in children after surgical intervention by conducting in vitro immune disorders, characterized in that for 3-4 days before surgery and one day after the operation, determine the content of CD 95 in the blood and when it is above 4.0% spend in vitro immunostimulatory effect on the auto leukocytes.

2. The method according to p. 1, characterized in that in vitro effects on the auto leukocytes carried out with the use of immunofan, or polyoxidonium, or any other immunostimulant.

 

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