Electrochemical detoxification in cancer patients after multiorgan surgery with severe endogenous intoxication

Background. Enteral insufficiency syndrome accompanies the development of many acute diseases of the abdominal cavity. According to the statistics, advanced and multi-organ surgical intervention in oncosurgery within the period from 2019 to 2020 resulted in enteral insufficiency being a complication in 39% of all cases, regardless of anatomical and physiological area, while complications in the form of endogenous intoxication syndrome made up 68% of cases. Purpose – studying the effectiveness of treatment of enteral insufficiency syndrome in cancer patients after multiorgan surgery with severe endogenous intoxication by means of indirect electrochemical detoxification with sodium hypochlorite solution. Materials and methods. The study involved 71 cancer patients who underwent multi-organ surgery on different anatomical and physiological areas. The patients were divided into 2 groups: treatment group (n=36) provided with indirect electrochemical detoxification by means of sodium hypochlorite solution at a concentration of 0.06%, comparison group (n=35) undergoing treatment according to standard schemes. The groups were comparable in age and anatomical and physiological areas that were operated on (surgery was performed on the chest and mediastinum as well as abdominal organs). Results. The method of electrochemical detoxification with sodium hypochlorite reducing the indicators that reflect blood toxicity and intoxication level was used for treating patients with enteral insufficiency. This was evidenced by decreased concentration of bilirubin by 23.1%, urea by 91.6%, creatinine by 99.4%, LII (leukocytal intoxication index) by 47.2% and procalcitonin by 68.2%. Being applied this method has made it possible to achieve a detoxifying effect early on day one. Conclusions. The findings of complete physical examination of cancer patients after multiorgan surgery with severe endogenous intoxication have shown a practical significance of sodium hypochlorite being included in comprehensive post-surgery treatment in enteral insufficiency syndrome cases. Infusions of 0.06% NaClO solution within 24 hours have been proved to provide a detoxifying effect: they significantly reduce elevated concentrations of bilirubin, creatinine, urea, LII and improve blood rheology. Administering sodium hypochlorite in the suppre-ssion of antioxidant defense mechanisms leads to the activation of oxidative processes. Including sodium hypochlorite in comprehensive post-surgery treatment in enteric insufficiency syndrome has shown a high efficiency.


INTRODUCTION
Enteral insufficiency syndrome (EIS) is a crucial factor in occurring endogenous intoxication and multiorgan failure [1][2][3]. In some cases, enteral insufficiency becomes one of the key pathogenetic factors threatening the life of a patient [4,5]. Thus, understanding the mechanisms of enteral insufficiency is essential in order to provide highly effective treatment of all diseases accompanying the development of this phenomenon. In recent years, clinical oncological practice has been actively developing in the direction of improving the quality of life of patients associated with antitumor treatment and after its completion. A great number of clinical and morphological forms of malignancies differ substantially by obvious endogenous intoxication. Due to intensifying the catabolic processes and accumulating toxic metabolic products, the quality of life of cancer patients significantly deteriorates [7].
Up to date, the number of advanced and multi-organ surgical interventions in oncosurgery is increasing. According to the statistics, surgeries involving the chest in 2018-2019 made up 47%, the abdomen -51%. Regardless of the location of surgery on different anatomical and physiological areas, enteral insufficiency manifests itself in 39% of all surgeries. Mortality from enteral insufficiency is approximately 46%, complications in the form of multiple-organ-failure syndrome (MOFS) -78% of cases. Compensated EI in the postoperative period occurs in 95%.
Detecting enteral insufficiency syndrome in patients operated on the chest and mediastinum stems from circulatory disorders during surgery and hypoxia, while in surgeries on the abdominal organs (AO), in most cases, it is due to translocation of bacteria resulting in enteral insufficiency.
As efferent therapy and resuscitation develop, there are opportunities for corrective influence on one or another body detoxification component. Studies in recent years have been focused on improving the effectiveness of detoxification using extracorporeal hemo-, plasma and lymphocorrection methods. However, in clinical presentation, there is no significant increase in the effect of the measures, which to some extent leads to the search for new effective methods aimed at reducing endotoxicosis and restoring the body's natural immunoreactivity [8]. Therefore, in recent years, more and more attention is drawn to electrochemical oxidation of biologically active substances, based on biochemical processes and patterns occurring in wildlife. Recently, among the tools and methods of efferent therapy, the method of indirect electrochemical detoxification, carried out by means of sodium hypochlorite solution, has become widespread. The main idea of the method is that oxidation by active oxygen underlies the vast majority of the body's vital processes associated with excretion of toxic components of exogenous or endogenous origin. Sodium hypochlorite has an oxidizing potential almost completely similar ISSN 2708-7166 (Print) ISSN 2708-7174 (Online)

МАТЕРІАЛИ ТА МЕТОДИ ДОСЛІДЖЕННЯ
У дослідження, яке проводилось на базі відділення онкологічної хірургії та відділення анестезіології з ліжками для інтенсивної терапії (ВАІТ) Державної to the oxygen potential, which makes it possible to achieve the goals of stimulating the natural mechanisms of detoxification and to simulate, to some extent, the detoxification function of the liver. The basis for its use is the ability to transform toxic metabolites, similar to the process of monooxygenase oxidation in the liver on cytochrome P-450, with translating the hydrophobic toxic products into hydrophilic and subsequent excretion of the latter ones from the body. Based on the mechanism of action, the scope of application of sodium hypochlorite in medicine is quite wide and it covers almost all critical conditions associated with acute and chronic toxicosis of various origins.
The method of infusion of sodium hypochlorite solutions is very promising in treatment of exo-and endotoxicosis. In particular, NaClO solutions have a direct and indirect antiaggregatory effect on platelets, inhibit leukocyte aggregation, enhance peroxidase oxidation in neutrophils.
Until the present, a great number of extracorporeal detoxification methods, based on the removal of endogenous toxins (ET) by purifying blood plasma, lymph and other media of the body, both directly and indirectly, have been introduced in the clinic to correct endogenous intoxication syndrome (EIS). However, mostly, these methods do not provide a comprehensive impact on ET. Plasmopheresis, hemodialysis, hemofiltration, hemosorption, and lymphosorption have the greatest total detoxifying properties. Plasmapheresis and erythrocytopheresis have the best detoxifying effect, while plasmapheresis and leukocytopheresis have the best immunocorrective effect [9,10]. Still the implementation of these procedures is accompanied by electrolyte imbalance and blood hormonal profile disturbance, trauma of blood cells, impaired blood clotting, need for catheterization of two central veins and/or thoracic lymphatic duct, loss with filtrate on the sorbent amino acids, proteins, lymphocytes and platelets, lymphorrhea, development of lymphatic fistulas, or disturbance of lymph circulation after drainage removal, etc.
Purpose -studying the effectiveness of treatment of enteral insufficiency syndrome in cancer patients after multiorgan surgery with severe endogenous intoxication by means of indirect electrochemical detoxification with sodium hypochlorite solution.
Досліджували показники, що відображають токсичність крові та ступінь інтоксикації при лікуванні Surgery Department and Anesthesiology Department with Intensive Care Beds of SO "Grigoriev Institute for Medical Radiology and Oncology of the National Academy of Medical Sciences of Ukraine" within the period from 2019 to 2020. There were 40 women (54.6%) and 31 men (45.4%). The patient population under study included 35 (48.9%) elderly patients; the treatment provided for those patients in postsurgery period was the most challenging due to natural biological, age-related changes and comorbidities.
The study was carried out in accordance with the ethical standards of the WMA Declaration of Helsinki on ethical principles for medical research involving human subjects The entry criteria were multiorgan surgeries on the chest, mediastinum and abdominal organs as well as the development of endogenous intoxication syndrome.
Withdrawal criteria: younger than 18, surgeries on only one anatomical and morphological area, the patient's reluctance to participate in the study; development of cardiovascular complications.
Depending on the treatment regimen, patients were divided into 2 groups: treatment group (n=36) provided with indirect electrochemical detoxification by means of sodium hypochlorite solution at a concentration of 0.06%, comparison group (n=35) undergoing treatment according to standard schemes.
At the baseline, the groups were comparable in age, sex and th elevel of surgical intervention. The study was performed in three stages: Stage I -before NaClO infusion, Stage II -1 hour after NaClO infusion, Stage III -4-6 hours after NaClO infusion.
Patients in treatment group underwent indirect electrochemical detoxification with sodium hypochlorite solution at a concentration of 0.06% by intravenous infusion. The infusion was performed into one of the central veins (subclavian, jugular, femoral) through a catheter at a rate of 50-70 drops per 1 min. The volume of the injected solution did not exceed 1/10 CBL per infusion.
The indicators reflecting blood toxicity and intoxication degree in treatment of intoxication syndrome by means of indirect electrochemical detoxification were studied. Ukrainian journal of radiology and oncology. 2021;29(2):52-61 ISSN 2708-7166 (Print) ISSN 2708-7174 (Online)
Statistical processing of the study findings was performed by means of accepted methods of statistical analysis in medical and biological studies using STATISTICA 13.3 EN and Microsoft Excel 2016. To describe and compare data sets, the arithmetic mean and its standard error (M ± m) were used. Accuracy of differences between mean values was considered to be significant at p <0.05.

RESULTS AND DISCUSSION
Blood toxicity parameters were assessed: creatinine, urea, total protein, bilirubin, glucose, osmolarity, blood clotting time, procalcitonin and leukocyte intoxication index. At stage I of the study, all above parameters were increased in both groups. It was ascertained that in treatment group and comparison group, LII index at stage I was comparable and equal to 4.60 ± 0.10 and 4.80 ± 0.20, respectively, which could be explained by forming enteral insufficiency syndrome within the first hours after surgery. Table 1 shows that at stage II (an hour after administering sodium hypochlorite solution, at concentration of 0.06%), improved acid-base balance (treatment group), decreased glucose concentration by 17-18%, prolonged blood clotting time by 40-60%, blood osmolarity decreased on average by 22-24 mosm/l are observed. In comparison group, no significant changes were observed (Table 2). Using NaCIO in order to detoxicate in the specified volume and concentration at stage II caused hypocoagulation. The development of hypocoagulation within the first hour (stage II) after NaCIO infusion indicates that it has direct anticoagulant properties. This should definitely be kept in mind by clinicians due to the risk of postoperative bleeding.
In treatment group, at stage III, a significant decrease in LII from 4.60 ± 0.10 to 1.60 ± 0.20 cu was observed. In comparison group, this figure remained almost unchanged. LII is one of the criteria of the functional state of the lymphocyte system indicating the ratio of lymphocytes to segmented neutrophils, i.e. the relationship between humoral and cellular parts of the immune system [9].
One of the most important and simplest indices, in terms of determining the parameters to evaluate intoxication, is the index of neutrophils/lymphocytes ratio, which reflects the ratio of cells of non-specific and specific defense of the body [10].
Changes in venous blood gas composition in treatment group suggest activating the respiration with a significantly increased p O2 level. i.e. from 73.30 ± 0.40 to 78.00 ± 0.60 mm Hg of venous blood at stage III. In comparison group, changes in venous blood gas composition were almost absent (Table 2).
Obviously, using NaCIO for detoxification in the specified concentration within the first 4-6 hours leads to hypocoagulation, hypoglycemia and improved rheological properties of blood.
Thus, analyzing the obtained data, it follows that administering a therapeutic dose of sodium hypochlorite (0.06%) enhances hypocoagulation and improves the rheological blood properties blood, as well as has a pronounced detoxifying effect (significant reduction in creatinine, urea, total protein, bilirubin, glucose, procalcitonin and leukocyte intoxication index) effectively correcting metabolic disorders and resulting in indirect immunocorrection.
Further studying the issue, search for effective concentrations depending on the clinical condition and laboratory parameters of cancer patients after multi-organ surgery in the postoperative period, the development of the algorithm of use are of high priority in modern oncosurgery and intensive care in general.

CONCLUSIONS
1. The findings of complete physical examination of cancer patients after multiorgan surgery with severe endogenous intoxication have shown a practical significance of sodium hypochlorite being included in comprehensive post-surgery treatment in enteral insufficiency syndrome cases.
2. Infusions of 0.06% NaClO solution within 24 hours have been proved to provide a detoxifying effect: they significantly reduce elevated concentrations of bilirubin, creatinine, urea, LII and improve blood rheology.