Efficacy of modified hemosorbents user for treatment of patients with multi-organ insufficiency

ЭФФЕКТИВНОСТЬ ИСПОЛЬЗОВАНИЯ МОДИФИЦИРОВАННОГО ГЕМОСОРБЕНТА В ЛЕЧЕНИИ БОЛЬНЫХ МУЛЬТИОРГАННОЙ

НЕДОСТАТОЧНОСТЬЮ

Ш.З. Касымов, З.Б. Курбаниязов,

С.С. Давлатов, Ш.А. Саидов

Республиканский специализированный Центр хирургии им. акад. В.В. Вахидова, Узбекистан Самаркандский ГМИ, Узбекистан

The treatment of patients with multiple organ failure is one of the most complex problems of modern medicine. The basic trigger of multiple organ failure syndrome is an excessive accumulation of endogenous toxins in the body and inability to excrete them by normal physiological routes [3]. Therefore, there is a real need for the application of methods of detoxification therapy, such as extracorporeal techniques of hemodialysis, hemofiltration and hemoperfusion, or hem-osorpuon. Hemosorption (HS) is an effective method of metabolic correction. It is fast and efficient in reducing the toxic load, and provides a favorable background for restoration of normal physiological metabolic reactions [2,5]. At the same time some clinicians consider hemosorption to he an aggressive method of efferent therapy, viewing the main obstacle for its wider use in medical practice in the complications associated with the development of a generalized inflammatory process. The main role in its genesis belongs to induction of blood humoral and cellular systems, particularly systems of contact activation as a consequence of interaction with a hemosorbent [1, 4]. A number of researchers also indicate a substantial degree of blood damage as it passes through the sorbent, which results in the reduction of platelets and red blood index. One of the ways of improving efficiency and safety of hemosorption is to modify physical and chemical properties of sorbents to increase their biocompatibility. The surface chemical oxidation of medical carbon adsorbents has been assessed as one of the promising methods of sorbent modification. This method allows the increase in the quantity of functionally active groups on the carbon surface and brings new properties and sorption mechanisms of detoxification [3]. At present there is a lot of controversy surrounding possible effects of surface oxidation of carbons on their biocompatibility: it is thought that oxidation of carbon sorbents is accompanied by reduction of blood damage during the sorption procedure, but this view is contradicted by other researchers [5]. The discrepancy of literature data and the urgency of this problem have induced us to study the hemosorption effects of the modified sorbenls on the condition of patients with multiple organ failure.

Experimental. Extracorporeal hemosorption on modified activated carbon hemosorbent was used in 31 patients (16 males and 15 females), 15-74 years of age (mean 36,2±3,1), who required intensive care in the postoperative period. All patients were treated in the City Hospital of Yangiyol, Uzbekistan, and were operated due to pathology of an abdominal cavity (n=15), purulent inflammatory diseases of soft tissues (n=11) and surgical pathology of genitals (n=5). The procedure of extracorporeal detoxification was required in 6 patients due to serious endogenous intoxication with progression of hepatic and renal insufficiency, and in 16 patients due to peritonitis. Postoperative complications included incompetence of scams of an anastomosis, sepsis, and hepatitis in 5 patients; and accompanying diseases such as cardiovascular insufficiency, diabetes and cirrhosis were found in 4 patients. The control group (n=25) was generated by a random sampling of case histories from a set of patients with a similar pathology, who were treated in our clinic according to standard hemosorption procedure using a nonmodified hentosorbent. Both groups were соmparable by gender distribution and age of the patients. The course of treatment consisted of two or three HS sessions with one day intervals. Hemosorption was carried out using a roller pump AKST-3 (Russia). Polymer pyгоlуzed activated carbon hemosorbent SKN-2 K, modified by oxidation, was used. The hemoperfusion column was connected to a veno-venous contour. The tlow rate of blood perfusion through the column was 80-100 ml/min, and duration of the first hemopeгfusion session was 40-50 min. Oxidative modification of the hemosorbent SKN-2 К was carried out using the technique developed by the authors. Briefly, immediately before the HS session, two liters of neutral anolite solution ON were perfused through the hemoperfusion column for 30 min. The ON anolite was obtained by electrochemical activation of a sodium chloride solution using "STEL-MT-IC" electrochemical unit (Russia). The concentration of the active chlorine generated in the solution was 300±50 mg/l. pH=6.5±0.5. The efficiency of treatment was judged by a decrease in the patients' subjective complaints, clinical symptoms of the disease and improved results of the laboratory tests. The lahoraiory tests were performed on patients' admission to the hospital, after the 1st hemosorption session and 24h after the 2nd or 3rd session. Immunoglobulins were measured using radial immunodiffusion in agar gel, and other parameters of homeostasis, immune and humoral response were measured in blood smears using standard laboratory protocols.

Results and Discussion. The severity of the initial clinical condition of patients in both groups was established by ihe biochemical and hematological indices in laboratory lests. Prior to hemosorption sessions all patients had substantial accumulation of endogenous toxic metabolites in their blood plasma due to the functional damage of vital organs. The majority of patients suffered from azotemia and biliru-binemia with the prevalence of direct fraction of bilirubin. Laboratory test revealed that 54% of patients had cholemic intoxication with the clinical signs of hepatic insufficiency, and 27% of patients had a disorder of nitrogen, protein and carbohydrate metabolism with characteristic signs of general toxemia. The assessment of basic hematological indicators and endotoxemia blood indices such as creatinine, urea and bilirubin in patients treated by standard hemosorption procedure revealed the insufficiency of its detoxification effect. Only after three hemosorption sessions (HS) were positive clinical dynamics and reduction of endotoxemia indices seen in patients of the control group. In the treatment group posi- tive clinical dynamics, reduction of endotoxemia indices and reduction of intoxication syndrome were achieved faster and to a greater extent than in the control group. It was suggested that the ON solution possesses hypocoagulation properties, therefore an additional study was undertaken to assess the effect of hemoperfusion through the modified carbon sorbent on the blood coagulation system and key homeostasis parameters. Tendency for normalization of blood indices in patients of the treatment group was noticeable alter the first HS session, and alter the second session full normalization was evident (Table 1). The immune system in the majority of patients was compromised by the initial condition (Table 2), as was evident by suppression of immunocompetent cells though it was not reflected in production of immunoglobulins IgA and IgM. As all the links and functions of the immune system are interconnected and depend on each other, a correlation analysis of the parameters studied was carried out.

A significant decrease in CD3/CD8 parity was noted. The indices of Th/Ts and CD3/CD4 were within a normal range. The depression of the general pool of CD3 cells in the studied group does not change the parity between a subpopulalion of T-cell helpers and the general pool of CD3 lymphocytes. Thus it can he assumed that CD4 cells preserve their immune-stimulating functions. The assessment of humoral immunity confirms this hypothesis. However the IgG level was lower and IgM and IgA levels were higher in the studied group when compared with the results for the control group. This саn be explained by an autoimmune aggression characteristic of hepatic pathology such as chronic liver lesion, as IgA and IgM are involved in formation of the immune complexes deposited in liver cell sinusoids and membranes thus provoking a cytopathic effect. Studying nonspecific immunity we noted the suppression of corresponding parameters of the immune system. The phagocytic activity of neutrophils (FAN) was considerably decreased which could lead to the development of infection. After hemosorption the activation of the immune system was noted and a significant increase in CD3, CD4 and CD19 lymphocyte numbers were seen. The level of immunoglobulins of all three classes also tended to increase, however only IgM growth was significant. It is possible that due to hemosorption and decrease in the levels of toxins and immune complexes, unblocking of the lymphocyte receptors occurs. This increases the production of lymphokines and improves their effect on immune cells leading to activation of cellular and humoral immunity noted in our experiments. Nonspecific immunity, as judged by FAN index, was also raised significantly. This could benefit patients by protecting them from bacterial infection. The immune system of patients with postoperative multiple organ failure is compromised, which is confirmed by the decrease of immunocompetent cells but not immunoglobulins IgA and IgM. Nonspecific immunity of these patients is also depressed. However, after extracorporeal blood purification had been performed, immune system stimulation was observed, which was higher than hemosorption specific indicators of cellular and humoral immunity. A substantial number of clinicians consider the removal of products of abnormal blood metabolism by hemosorption as a major factor оf its clinical outcome. However the effect of direct detoxification on pathological process could be compromised because not only toxic substances but some of the circulating immune complexes, immunocompetent cells and biologically active substances are also removed from the blood.

Hemosorption performed using the modified sorbent revealed a number of advantages over conventional hemoperfusion. These include positive dynamics of clinical characteristics expressed in reduction of complications, improvement of general health and main biochemical and immunological parameters. Normalization оf blood indices and reduction of level of endogenous intoxication in patients of the treatment group was seen after the first hemoperfusion session and after the second session the full normalization was evident. The changes in the chemical structure of the modified sorbent underlie the positive clinical changes in patients who have undergone hemoperfusion through the modified sorbent. By ircaiing the activated carbon with anolite ON, an inclusion of acid groups into the hemosorbent surface structure occurs, which provides additional oxidizing properties. The described modified extracorporeal hemoperfusion promotes stimulation of cellular and humoral immunity and mobilization of protective systems of an organism.

Table 1

Effect of hemoperfusion through the modified carbon sorbent on the blood coagulation system

Table 2

Indices of cellular and humoral immunity before and after hemosorption

T h – helper T cells (CD4), T s – suppressor T cells (CD8), FAN – phagocytic activity of neutrophils, CD3 T-lymphocytes, CD19 – B-lymphocytes.

Therefore the HS through the modified sorbent is more effective and has an effect on the main parameters of the hemostasis system when compared with conventional techniques. This procedure of blood purification also acts as a replacement for the functions of a failed organ of the patient. Modification of the activated carbon sorbent by neutral anolite solution in situ solves another important problem associated with the need to use anticoagulants for prevention of thrombosis within a hemosorbent. Oxidizing modification of carbon with ON solution considerably reduces the required doses of anticoagulants such as heparin or solutio glugicirum (a solution of 2% of sodium hydrocitrale and 3% glucose) and decreases the risk of postoperative complications associated with an imbalance of the coagulation system. The described sorbent modification technique by using neutral anolite solution improves the efficiency of blood detoxification and improves treatment results in patients with the signs of an endogenous intoxication syndrome. The treatment duration was reduced by 41% using the modified hemosorbent in comparison with the control group. The hospitalization time was reduced 4,8-fold after hemosorption over the modified sorbent.

Conclusions. The described sorbent modification technique by using neutral anolite solution improves the efficiency of blood detoxification by hemosorption. It has a stimulating effect and improves treatment results in patients with multiple organ failure. Hemosorption through the modified sorbent has a sparing effect on the homeostasis system and causes minimal adverse blood reactions when compared with conventional hemosorption.