Use of Atoxil in complex treatment of burns

APPLICATION OF THE DRUG «ATOXYL» IN THE COMPLEX TREATMENT OF BURNS.

E. Ya. Fistal, I.I. Speransky, V.V. Arefiev, E.G. Tymoshenko, M.V. Lobachev Institute of Emergency and Restorative Surgery named after V.K. Husaka, AMS of Ukraine, Donetsk

Introduction. Burn victims are one of the most difficult categories of patients in surgical practice. The problem of general and local treatment of burns, prevention of infections complicated by this pathology remains relevant at the present time. Despite the presence of highly effective antibiotics, the number of patients with purulent complications has practically no tendency to decrease. This is due to various factors, such as an increase in the number of antibiotic-resistant strains of pathogenic microorganisms; the absence of the possibility of purchasing highly effective antibiotics due to their high cost; certain difficulties in creating the optimal concentration of antibiotics in the lesion; violation of the body's immune reactivity, etc.

According to modern ideas, endogenous intoxication plays an important role in the pathogenesis of burn disease. The main source of endogenous intoxication is a burn wound, the periwound zone, the microbial flora of wounds and the products of their vital activity [4, 5, 8, 11]. However, recently there have been many works on the involvement in the formation of the intoxication syndrome in burns of the alimentary canal [1,2, 4, 7, 11].

Deep or extensive burns cause significant violations of water-salt exchange in the body, and the endogenous and exogenous intoxication that develops at the same time leads to a violation of the function of organs and systems at the morphofunctional level [3,4], inhibits intracellular regenerative processes in cells [12]. Therefore, the use of drugs that reduce the level of toxins in the body is promising in the treatment of thermal injuries.

Among the many methods and methods of efferent therapy, a special place belongs to enterosorption and local application of various sorbents [10], which differ in chemical nature, manufacturing method and are different modifications of activated carbon, ion exchange resins, silica, natural and synthetic materials. Recently, a number of preparations with an adsorption effect have appeared, which hold adsorbed substances at the boundary between the liquid and solid phase. According to the literature, their use contributes to the reduction of intoxication in various stages of burn disease and faster cleansing of wounds and their preparation for autodermoplasty [6,8,9]. One of the sorbents that can be used both topically and orally is ATOXYL, which is produced by OAO Lviv Pharmaceutical Factory, LLC Orysil Pharm.

The purpose and tasks of the research: The purpose of this research was clinical assessment of the effectiveness of the ATOXIL drug for general and local treatment of burns and their complications, study of the ATOXIL drug's tolerability, and identification of side effects when using it.

The main tasks of the study were:

1. On the basis of clinical and laboratory studies, draw conclusions about the effectiveness of the drug ATOXIL in the general and local treatment of burns of various localization.
2. Evaluate the tolerability and safety of using the ATOXIL drug in burns at various stages of burn wound treatment;
3. 3. Develop schemes for the use of the drug ATOXIL depending on the severity of the burn disease, the presence or absence of inflammatory complications, and the phase of the wound process.

ATOXIL is a light amorphous powder of white color, tasteless and odorless in glass bottles with a capacity of 250 ml. 1 bottle contains 12.0 highly dispersed silicon dioxide powder.

ATOXYL is an enterosorbent with pronounced sorption properties, exhibits detoxification, antimicrobial and wound-healing effects. It adsorbs from the digestive tract and removes from the body endogenous and exogenous toxic substances of various origins, has high adsorption activity against microorganisms and proteins, including microbial toxins. At the same time, the desorption of bound proteins and toxins is hindered both through the wound and through the intestinal walls. Facilitates transport from the internal environment of the body (blood, lymph, interstitium) to the digestive tract due to concentration and somatic gradients of various toxic products, including medium molecules, oligopeptides, amines and other substances with subsequent elimination from the body. It is practically not absorbed from the intestines and wounds.

Materials and research methods.

An analysis of the immediate results of the treatment of 125 patients with burns of different localization, depth and area of the lesion, who were treated in the Department of Thermal Injuries named after V.K. Goose of the Medical Academy of Ukraine during 2005 and the first quarter of 2006. The age of patients ranged from 21 to 75 years. The etiological factor of the injury was flame – in 72 patients, hot liquids – in 50 victims, electric trauma in 3. The groups were created arbitrarily, as the victims entered the hospital. The clinical characteristics of the observed groups were completely comparable in terms of age and quality, which made it possible to conduct a comparative analysis in the future. Comparison of the victims by age, nature of the main lesion and accompanying pathology did not reveal any significant differences. Men of working age predominated, which was characterized by the nature and place of injury.

The criterion for the inclusion of patients in the study groups was burns localized on the extremities in the first hours from the moment of injury, burns with the presence or threat of developing infectious complications of both local and general nature. First of all, patients with severe manifestations of intoxication were included.

Patients are divided into four groups:

The first group - 35 victims with medium-severity burns (total area of damage up to 30% of the body surface, of which deep up to 10%), in addition to the generally accepted principles of treatment of this pathology, in order to reduce the manifestation of intoxication syndrome of various genesis, additionally received the drug ATOXIL. The drug was diluted in 250.0 ml of drinking water or 0.91 TP3T sodium chloride solution and given to patients in 50–75 ml 3–5 times a day 1–1.5 hours before meals or oral medication depending on the clinic of the intoxication syndrome. The obtained suspension was injected into the nasogastric tube of five victims in a state of alcoholic intoxication. The course of treatment varied from 3 to 7 days, which was determined by the clinic of the intoxication syndrome.

The second group - 30 patients (control group) was treated according to the generally accepted method, including the oral use of the drug ENTEROSGEL for the treatment and prevention of intoxication syndrome of various genesis.

The third group – 38 people received local treatment with ATOXIL. After careful toileting of the wound, removal of necrotic tissues, the wound was treated with an antiseptic (10% betadine solution or 2% boric acid solution or 30% bactosyn solution), dried with sterile tampons. Then, with a spoon, ATOXIL was applied to the wounds in a layer 0.5–0.8 cm thick. The thickness of the ATOXIL layer depended on the amount released from the wound, its microbial insemination, and the phase of the wound process. The more that is separated, the thicker the ATOXIL layer. A dry aseptic bandage or a bandage with a water-soluble ointment was applied on top. Dressings were changed daily, especially if polyethylene food film was additionally used to speed up the process of cleaning the wound.

The use of polyethylene food film contributed to the increase of what is released from the wound, the creation of a "wet chamber", which led to faster rejection of necrotic tissues and the early appearance of edge and island epithelization of the wound. In addition, the gauze napkin placed on the layer of ATOXIL did not stick to the wound and the dressings became painless, there was no bleeding from the granulations.

The fourth group - 22 patients (the second control group) locally received generally accepted treatment - bandages with dermazin, levomekol, 2% boric acid or 30% Bactosin solution.

When taking into account the effectiveness of the treatment, the beginning of cleansing and marginal epithelization (the day of appearance), their speed, improvement in the general condition and well-being of the patient, normalization of temperature and clinical and laboratory parameters, the terms of the final healing of wounds or their preparation for surgical intervention were taken into account. In addition, the effectiveness of local treatment was evaluated on the basis of subjective (general condition of the patient, visual assessment of the wound) and objective (qualitative and quantitative composition of the wound microflora, dynamics of wound prints - on the 1st, 3rd, 5th, 7th day) criteria. The appearance of epithelization of burn wounds 4–5 days earlier compared to the control and a reduction in the duration of treatment by 6–10 days were considered effective.

General and biochemical analyzes of blood and urine were performed on all patients before the appointment of treatment and on 2, 4–5, 7–8 and after the end of treatment, including the determination of medium molecules in erythrocytes, plasma and urine, control of temperature, pulse, pressure, cytological examination of the wound by the method of prints. To estimate the level of endogenous intoxication based on a detailed general blood analysis, the leukocyte index was calculated, which reflects the relationship between the humoral and cellular links of the immune system; Krebs index, blood cell indicator, leukocyte index of Calf-Kalif intoxication (LII) as an indicator of tissue degradation processes, level of EI; modified LII (LIIm), reactive response of neutrophils (RON), body resistance index (IRO), hematological index of intoxication (HPI), blood leukocyte shift index (ISLK), as an indicator of the activity of the inflammatory process and impaired reactivity of the immune system; the index of the ratio of leukocytes and ESR (ILSOE), which allows judging about EI associated with an infectious or inflammatory process. To facilitate the calculation of these indicators, a program for computer processing of leukocyte formula data was developed with the aim of obtaining intoxication indices.

Results and their discussion.

Patients of the first group were characterized by a reduction or disappearance of the intoxication syndrome caused by alcohol intoxication after taking 6.0–12.0 g of the drug ATOXIL during the first day and a decrease in the symptoms of intoxication of mixed genesis after taking 12.0–24.0 g of the drug on the third–fourth day. This was manifested by a decrease in body temperature, indices of intoxication — LII, LIIm, ILSOE, RON, etc., normalization of indicators of medium molecules at 25–35%.

It was also noted that the phase of inflammation (exudation) in this group of victims occurred with less plasma loss, the perifocal inflammation characteristic of this phase of the wound process was less pronounced.

In the stage of septicotoxemia, the enterosorbent contributed to even greater activation of compensatory and adaptive processes of the body. At the same time, the number of episodes of sudden temperature rise and chills, swings between morning and evening temperature decreased. The time for the formation of a dry burn scab was 2.4 ± 0.3 days less than in the control group.

The drug ATOXIL was prescribed to five patients for the prevention or cessation of alcoholic delirium or encephalopathy of mixed genesis together with 10.0–20.0 ml of L-lysine escinate intravenously for 2 days. It was noted that after the first or second intravenous injection of 10.0 ml of L-lysine escinate solution and taking 100.0–200.0 ml of ATOXIL suspension, an increase in the level of consciousness was noted, the patient became more accessible to productive contact, motor-speech stimulation decreased. After a 3–5-day course of treatment, 4 patients managed to completely stop the phenomena of acute alcoholic delirium.

The tolerance of oral administration of ATOXIL was good, no local or general reactions were detected in the patients of the study group.

In patients of the second (control) group, the phenomena of endogenous intoxication decreased more slowly. In order to reduce intoxication, 25 patients were prescribed enterosorption with ENTEROSGEL for 1–2 tbsp. l. 3 times a day with simultaneous intake of sorbitol 15.0 3 times a day. At the same time, it was noted that on the 4th–7th day of treatment, the indicators of the average molecules did not differ significantly from the initial ones, and sometimes even worsened. Clinically, this manifested as a disturbance of consciousness in the form of encephalopathy, delirium, etc. Integral indices — LII, LIIm, ILSOE, RON came to normal on the 5th–8th day. At the same time, phenomena of perifocal inflammation and increased exudation from wounds were more often observed, and hyperthermia persisted. In patients who received ENTEROSGEL, bloating of the intestines was noted, and in five patients, intestinal paresis was expressed, despite the stimulation of the intestines and daily cleansing enemas. This required an additional prescription of drugs and cleansing enemas.

In the patients of the third group, the reduction of pain occurred on the second-third day after the application of ATOXIL to the wound. At the same time, an increase in exudate from the wound was noted, it became more viscous, thick, and dark in color. When sprinkled on a wet scab with an area of up to 30 cm², it either dried up within a day, or it began to dry more quickly and/or with areas of melting already on the 4th to 7th day of treatment.

The body temperature was kept within the range of 37.8–38.5 °C for 4–6 days, sometimes antibiotics were required. The times of scab rejection and complete healing of superficial wounds were 5 ± 2.9 days less than in the control, perifocal inflammation and exudation were moderately expressed. There was a decrease in the severity of intoxication for 3–4 days, normalization of EI indicators — LII, RON, ILSOE.

The tolerability of local application of ATOXIL was good in all patients: none of the patients had general or local manifestations of allergies, unpleasant sensations, itching.

The effectiveness of local treatment was assessed on the basis of subjective (visual assessment of the wound condition) and objective (qualitative and quantitative composition of the wound microflora, dynamics of wound prints — on the 1st, 3rd, 5th, 7th day) criteria.

Cytological prints in patients with fresh burns on the first day from the moment of injury (12–24 hours) showed the presence of fibrin threads, single cell membranes, and places where they accumulated up to 10 in the field of vision. All cells did not contain nuclei and were elements of destruction during the burn. In some prints (when admitted on the second to third day after receiving a burn), the processes of necrolysis, the presence of segmented leukocytes with various degeneration of the nucleus, and the accumulation of microflora located extracellularly prevailed. As the scab formed and dried, it was not possible to get an impression.

In patients of the second and third groups, in the presence of an inflammatory reaction around the burn scab with abundant and/or moderate serous-purulent discharge, the presence of leukocytes from ¼ of the field of vision to a continuous cluster on the entire field of vision, with a predominance of neutrophils, was noted in the prints. Most leukocytes were degeneratively changed. Extracellularly there were cocci and rods.

By the 4–5th day of treatment with ATOXIL, the vast majority of patients (33, or 86.8%) of the second group noted the elimination of perifocal inflammation, a decrease in the amount of secretion, cleansing of wounds from fibrin deposits and point areas of necrosis, and the appearance of bright fine-grained granulations all over the wound surface. Cytological examination of wound prints already after 1–3 dressings with ATOXIL showed a pronounced cleansing of the exudate from microflora, tissue detritus and destroyed neutrophils, increased phagocytosis of microbes, an increase in the number of active macrophages, and then also fibroblasts. In the majority of patients, the specified changes corresponded to a rapid transition from the inflammatory-necrotic to the inflammatory-regenerative and regenerative types of cytograms by the 3rd–5th day. All this testified to the transition of the wound process to the second phase and was a criterion for the readiness of the wound for surgical closure. In 4 observations (10.5%), the development of the purulent process continued, which required surgical treatment, then dressings with ATOXIL were resumed.

In the fourth group of patients (the second comparison group), who received traditional local treatment - local irrigation of wounds with an aerosol "Polcortolon" or "Oxycort" - the pain factor lasted for 2–3 days, drying of the scab occurred on 3–5 days, moderate exudation and perifocal inflammation persisted. Patients who were treated with bandages of dermazin, levomekol, synthomycin emulsion noted a feeling of tightness, which worsened their well-being and disturbed sleep. Half of the patients had swelling around the burn wound for 7–10 days. The temperature of 37.8–38.5 °С was maintained for 7–10 days, almost all of them received antibiotics. Self-healing of the scab occurred 10–20 days after the burn, hyperemia of the healed areas persisted for a long time.

In order to reduce intoxication, 5 patients were prescribed enterosorption with ENTEROSGEL for 1–2 tbsp. l. 3 times a day with simultaneous intake of sorbitol 15.0 3 times a day. At the same time, it was noted that on the 4th–7th day of treatment, the indicators of the average molecules did not differ significantly from the initial ones, and sometimes even worsened, which was clinically manifested by impaired consciousness of the victims in the form of encephalopathy, delirium, etc. In 2 patients, intestinal paresis developed, which required additional prescription of drugs and cleansing enemas.

During cytological examination of prints from the wounds of this group of patients in 17 patients (77,27%), despite the decrease in bacterial contamination of the wounds, by the 4th–5th day of treatment, a sluggish cleansing of the wound was noted, in some places fibrin deposits on poorly developed granulation tissue. Moreover, 7 patients (18,18%) required repeated surgical treatment. The predominant type of cytograms, even on the 7th day, was inflammatory (49%), less often — inflammatory-regenerative (32%), even less often — regenerative-inflammatory (12%) and regenerative (7%) types of wound imprints. Thus, only in 2 patients of the comparison group on the 5th day of treatment, the conditions for carrying out restorative operations were created.

The general analysis of urine in the three groups was within the norm and did not depend on the treatment methods. In the general blood analysis, various manifestations of the inflammatory reaction were noted, which depended on the area of the total burn, the stage of the burn disease and did not significantly depend on the method of local treatment of burns in all groups of victims.

The results of this clinical study indicate that ATOXIL is an effective agent for the treatment of burns in various stages of burn disease, local application promotes earlier epithelization of superficial burns and preparation of deep and complicated burn wounds for surgical intervention.

Conclusions and recommendations.

1. As shown by clinical and laboratory observations, the drug ATOXIL is effective in the complex treatment of burns and the prevention of infectious complications in burned patients.
2. The drug ATOXIL is satisfactorily tolerated by patients, we did not observe side effects in the patients of the study group. It does not cause painful sensations when using it, on the contrary, it has an analgesic effect, does not form fatty films that prevent the outflow of edematous fluid, and therefore can be used in the first hours from the moment of receiving a burn, while foaming and fat-containing aerosols only after 5-8 days.
3. The drug ATOXIL has a convenient package that allows you to dose the consumption of the drug and fully use the contents of the bottle.
4. We consider it expedient to use the drug ATOXIL in the complex treatment of burns.

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Information about the authors

1. Fistal Emil Yakovlevich, doctor of medical sciences, professor, head of the Department of Thermal Injury and Plastic Surgery of the Donetsk Medical University named after M. Gorky, head of the Department of Thermal Injuries at the Institute of Emergency and Restorative Surgery named after V.K. Goose of the Academy of Medical Sciences of Ukraine
2. Igor Igorevich Speransky, senior resident of the burn department of the Institute of Emergency and Restorative Surgery named after V.K. Husaka AMS of Ukraine: 83121, Donetsk-121, str. 18 Party Congress, house 12, tel. rab: (0622) 66-01-54, tel. home: (0622) 57-76-16, mobile 8-066-49-56-410
3. Victor Vladimirovich Arefiev, head of the burn department of the Institute of Urgent and Restorative Surgery named after V.K. Goose of the Academy of Medical Sciences of Ukraine
4. Tymoshenko Elena Georgievna, laboratory doctor of the highest category of the clinical laboratory of the Institute of Emergency and Restorative Surgery named after V.K. Goose of the Academy of Medical Sciences of Ukraine
5. Maryna Vladimirovna Lobacheva, student of the Donetsk National Technical University, Faculty of Computer Information Technologies and Automation