Dioxidin, 1 piece, 30 g, 5%, ointment for external use
Ointment
Locally. Apply a thin layer to the affected area once a day. Course - up to 3 weeks.
Solution for infusion and external use, 5 mg/mg
IV,
drip. In severe septic conditions, the drug solution is administered, previously diluted in a 5% dextrose solution or in a 0.9% sodium chloride solution to a concentration of 0.1–0.2%. The highest single dose is 300 mg, the daily dose is 600 mg.
Externally
— deep wounds are packed or irrigated with a solution daily or every other day, depending on the condition of the burn wound and the course of the wound process. The maximum daily dose is 2.5 g. Duration of treatment is up to 3 weeks.
Solution for intracavitary and external use 10 mg/ml
Externally, intracavity.
Dioxidin® is prescribed in a hospital setting.
Dioxidin® 1% solution cannot be used for intravenous administration due to the instability of the solution when stored at low temperatures.
Intracavitary administration.
Depending on its size, 10 to 50 ml of a 1% Dioxidin® solution is injected into the purulent cavity per day. Dioxidin® solution is injected into the cavity through a catheter, drainage tube or syringe. The maximum daily dose for administration into cavities is 70 ml of a 1% solution. The drug is administered into the cavity usually once a day. According to indications, it is possible to administer a daily dose in two doses. If well tolerated, the drug can be administered daily for 3 weeks or more. If necessary, repeat courses are given after 1–1.5 months.
External use.
Use 0.1–1% solutions of Dioxidin®. To obtain 0.1–0.2% solutions, ampoule solutions of the drug are diluted to the desired concentration with a sterile 0.9% sodium chloride solution or water for injection.
To treat superficial infected purulent wounds, apply napkins moistened with a 0.5–1% solution of Dioxidin®. After treatment, deep wounds are loosely tamponed with napkins moistened with a 1% solution of Dioxidin®, and if there is a drainage tube, 20 to 100 ml of a 0.5% solution of the drug is injected into the cavity.
For the treatment of deep purulent wounds with osteomyelitis (wounds of the hand, foot), use 0.5–1% solutions of the drug in the form of baths or carry out a special treatment of the wound with a solution of the drug for 15–20 minutes (injection of the solution into the wound for this period) followed by application dressings with 1% Dioxidin® solution.
Dioxidin® in the form of 0.1–0.5% solutions can be used to prevent and treat infections after surgery. According to indications (patients with osteomyelitis) and if well tolerated, treatment can be carried out daily for 1.5–2 months.
Dioxidine
Dioxidin is a broad-spectrum antimicrobial drug, chemically related to quinoxaline derivatives. Suppresses the growth and reproduction of a number of infectious agents, including dysentery and Pseudomonas aeruginosa, Proteus vulgaris, Klebsiella, Salmonella, and staphylococci. streptococci, pathogenic anaerobic bacteria (among which the causative agents of gas gangrene should be distinguished). The chemotherapeutic activity of dioxidin also extends to bacterial strains that exhibit resistance to other antibacterial drugs. At the same time, a number of microorganisms can develop resistance to dioxidin itself. The intravenous form of the drug is characterized by a narrow range between therapeutic and toxic dosages, therefore it is necessary to strictly adhere to the doses recommended by the doctor or the instructions for use. When applying dioxidine ointment to the skin or when injecting it, there is practically no irritation of the skin at the injection site. The drug is widely used as a treatment for burns and purulent wounds with necrotic tissue degeneration that has already begun: it cleans the surface of the wound in the shortest possible time, stimulates tissue restoration, incl.
including epithelial, has a beneficial effect on the wound healing process.
Dioxidin is available in the form of a solution for infusion and external use and ointment. The drug is prescribed only to adults and only for serious infectious diseases of severe origin and in case of ineffectiveness of previous antibiotic therapy using fluoroquinolones, carbapenems, and cephalosporins of II-IV generations. It should be noted that dioxidin has teratogenic, mutagenic and embryotoxic effects, which has been confirmed in a number of experiments. If the patient has a history of chronic kidney failure, the dose of the drug must be adjusted downward. During storage of dioxidine solution, crystalline precipitate may form. In such cases, the ampoule with the solution must be heated in a boiling water bath until the crystals completely disappear. If after cooling the solution the crystals do not fall out again, then the drug can be used for its intended purpose. The possible appearance of pigment spots can be eliminated as follows: increasing the time of a single administration of dioxidine up to 2 hours, reducing the dose, prescribing antihistamines or completely stopping the drug.
Trophic ulcers, according to the combined classification of skin and soft tissue infections, are classified as secondary complicated infections [3], i.e. they are not an independent disease, but arise during the progression of another disease (diabetes mellitus, obliterating atherosclerosis of the lower extremities, chronic venous diseases, etc.). Trophic ulcers of venous etiology are a defect of the skin and underlying tissues of the leg, resulting from a chronic disorder of the venous outflow. They complicate the course of chronic venous insufficiency (CVI) in 15-18% of cases and occur in 1-2% of the adult working population and in 4-5% of elderly patients. Generally accepted methods of treating trophic disorders caused by chronic venous disease (CVD) are aimed at the main links of pathogenesis in order to eliminate one of the main causes of the development of CVI - venous hypertension, the long-term existence of which leads to changes at the tissue, cellular and microcirculatory levels and ultimately to tissue destruction. To correct these disorders, a set of measures is used: compression treatment, systemic pharmacotherapy, and surgery [4].
Local treatment of the ulcer and periulcerous tissues with various topical medications and/or wound dressings is a key step in treatment. The choice of specific therapeutic agents depends on the characteristics of the wound process, the condition of the tissues surrounding the trophic ulcer, and the limb as a whole. In our country, the most common and accessible method for its simplicity and economic costs, despite its inherent disadvantages, is the use of various topical medications (drainage sorbents; proteolytic enzymes; antiseptics) in the practice of a Russian surgeon. - solutions, pastes, powders; ointments; aerosols; regeneration stimulants). Recently, publications have appeared in domestic and foreign literature on the use of a new generation of antiseptic drugs that have a combined effect. Over the past half century, the number of such drugs has increased significantly, but the healing time for ulcers in most patients averages about 2-3 months, in some patients they do not heal for years, and the relapse rate with conservative treatment reaches 60-70%.
The microbiological structure of the surface of venous ulcers almost always has a wide range in the form of associative aerobic-anaerobic microflora with a level of microbial contamination of 107-108 per 1 g of tissue. Gram-positive microorganisms predominate (60.8%). In most cases, the development of purulent-inflammatory complications is caused by Staphylococcus aureus
(58.4%),
Pseudomonas aeruginosa
(17.2%),
Proteus mirabilis
(12.9%). Along with this, in patients with CVI, almost 75% are diagnosed with a mycotic infection, which sensitizes the body and aggravates the severity of the wound process. Symbiotic microorganisms present in venous ulcers, as a rule, do not cause signs of inflammation and do not have a significant effect on the rate of healing.
It has been established that the use of local antibacterial drugs in patients with venous ulcers should not be routine, as this leads to the emergence of resistant strains of microorganisms, prolongation of the inflammation phase, suppression of protective immune mechanisms and, as a consequence, inhibition of regeneration, the appearance of signs of the process becoming chronic state. Regular use of antiseptic solutions (miramistin, chlorhexidine, hydrogen peroxide) for the purpose of sanitation of ulcers during dressing or treatment has a cytotoxic effect on granulation tissue and inhibits proliferation [2, 5], increasing the risk of contact dermatitis. Only in the case of the addition of an infection, clinically manifested in the form of a systemic and/or pronounced local inflammatory reaction both in the ulcer itself and in the surrounding tissues (acute indurative cellulitis), signs of paratraumatic microbial eczema and pyoderma, does the need arise for local use of antiseptic and antibacterial drugs independently or as an adjunct to the administration of systemic antibacterial therapy [1, 6]. In these cases, accelerating the ulcer healing process can be more effective due to a more rapid transition from stage I of the wound process to stage III-III, granulation and epithelization due to a decrease in microbial contamination, relief of signs of inflammation, cleansing the ulcer surface from purulent-necrotic masses, fibrin, removal excess exudate.
It has been proven that the use of modern wound coverings, which create and maintain conditions in the wound that are optimal for autolytic cleansing and regeneration, close to physiological (hydrogels, alginates, hydrocolloids, etc.) actually accelerates the healing time. However, due to the low availability in the pharmacy chain and the relatively high cost, lack of experience, their widespread use in the daily practice of a surgeon is problematic. In this regard, it deserves attention and targeted study of the possibilities of using “old” antiseptic drugs in phlebological practice for the local treatment of purulent wounds.
We conducted a clinical study, the purpose of which was to study the effectiveness of the drug dioxidin, 1% solution, and dioxidin, 5% ointment (MIR-PHARM LLC, Russia), in patients with trophic ulcers of venous origin in the first stage of the wound process.
Material and methods
Dioxidin is a synthetic broad-spectrum antibacterial drug that is used to treat various forms of purulent infection. It has a bactericidal effect, causes structural changes in the cell wall and nucleotide of bacteria, selectively inhibits DNA synthesis in the microbial cell without affecting the synthesis of RNA and protein. Dioxidin is active against gram-negative, gram-positive pathogenic and opportunistic aerobic and anaerobic microorganisms of spore-forming and non-spore-forming species. It remains active against strains resistant to other antimicrobials, including antibiotics. Cross-resistance between dioxidin and other antimicrobial drugs has not been established.
We carried out outpatient treatment of venous ulcers in 30 patients (stage I of the wound process) for 2 weeks with bandages with a 1% dioxidine solution or 5% dioxidine ointment. Among them there were 11 men and 19 women. The age of the patients ranged from 36 years to 71 years (mean age 59.7 ± 9.4 years). The history of CVI was documented in the range from 5 to 40 years and averaged 17.87±8.7 years. The area of the ulcerative defect ranged from 5.1 to 19.32 cm2 (average 7.91±5.3 cm2). The duration of ulcer history varied from 2 to 54 months. In 18 (60%) patients, the ulcer was recurrent, of which in 4 it did not heal for several years.
Throughout the study, along with local treatment, all patients mandatory used elastic compression of the lower extremities in the form of bandaging and systemic pharmacotherapy (micronized purified flavonoid fraction of diosmin 1000 mg per day). The main clinical characteristics of the patients are presented in Table. 1
.
In 18 (60%) patients, ulcers were a complication of varicose veins of the lower extremities, and in 12 (40%) - postthrombophlebitic syndrome.
In all patients, the ulcers were located on the medial surface of the lower third of the leg. At the start of treatment, the clinical picture of the ulcer in 16 patients was characterized by the presence of fibrinous and fibrinous-purulent deposits, intense or moderate serous-purulent discharge, single granulations and lack of epithelization. In 4 patients, the bottom of the ulcerative defect was represented by necrotic masses with pronounced perifocal inflammation and profuse fibrinous-purulent discharge; in 10 patients, there was an overlay of loose fibrin on flaccid granulations, there was initial marginal epithelization, and varying degrees of serous-purulent discharge. Along with this, at the initial stage of the study, 26 patients complained of pain, a feeling of heaviness and discomfort in the area of the trophic ulcer.
Clinical monitoring of the wound was carried out every 4-5 days for 2 weeks: they examined and measured the area of the ulcerative defect, noted the presence of fibrin, the severity of granulation, epithelialization, the nature and amount of wound discharge, the condition of surrounding tissues, and the presence of local adverse events. Along with this, subjective data were assessed: the degree of discomfort in the patient’s daily life (using a 10-cm visual analogue scale), pain syndrome in points. All patients underwent microbiological and cytological examinations at the beginning and end of treatment, and ultrasound examination of the veins of the lower extremities.
The dressing regulations depended on the intensity of exudation, the presence of pain and the degree of discomfort in the ulcer area. In case of severe exudation, dressings were carried out 2-3 times a day, in case of moderate or scanty exudation, the appearance of granulation tissue and areas of marginal epithelialization - 1 time a day.
Inclusion criteria:
men and women aged 18-75 years, undergoing outpatient treatment and having trophic ulcers of the lower leg of one or both extremities with a diameter of 5-20 cm2, at least 2 months old, ready to follow the doctor’s instructions regarding the prescribed therapy.
Exclusion criteria:
patients whose general serious condition due to somatic diseases did not allow them to comply with the recommended regimen; the patient has diabetes mellitus, obliterating atherosclerosis of the lower extremities (ABI <0.8), hypersensitivity to dioxidin, lack of willingness to cooperate on the part of the patient.
results
All patients completed the study. After 2 weeks of treatment of venous trophic ulcers with a 1% solution of dioxidine and 5% dioxidine ointment, complete cleansing of the ulcerative defect from purulent-necrotic ulcers and fibrin occurred in 21 (70%) patients. The course of the wound process in patients in this group was the most favorable. Along with cleansing, a significant decrease in pain was noted (on average from 2.13 to 1.0 points), a decrease in the degree of discomfort (on average from 7.0 to 3.0 cm on a 10-cm scale). Against the background of cleansing, activation of reparative processes was documented in the form of growth of granulation tissue and the appearance of marginal epithelialization, which led to a reduction in the area of the ulcerative defect from an average of 7.9 to 6.8 cm2 (Table 2)
.
In 7 (23%) patients, the area of the ulcer defect remained the same. The cleansing process did not proceed as quickly as in the previous group. Initially, in these cases there were pronounced changes in the periulcerous tissues in the form of dermatitis, lipodermatosclerosis, which supported inflammation and provoked pain and discomfort. At the same time, patients in this group also documented cleansing of the ulcer surface from pus, necrotic tissue, a decrease in the degree of compaction of surrounding tissues, and a zone of hyperemia around the wound. It should be noted that by the beginning of the 2nd week of treatment with the drug, despite minor changes in the area of the ulcer, all patients noted a decrease in pain and discomfort in the ulcer area; by the end of the 2nd week of treatment with dioxidine, the nature of the wound discharge noticeably changed (from fibrinous-purulent to serous), pain decreased, active succulent granulations appeared.
The rate of cleansing of the ulcer surface was uneven and depended mainly on the area of the defect and the condition of the surrounding skin. More rapid cleansing of purulent-necrotic tissue, the appearance of granulations, and marginal epithelization were observed in small ulcers (from 5 to 8 cm2) with unchanged surrounding tissues (two of which were superficial and by the end of treatment were almost completely covered with a thin layer of epithelium).
We compared the effectiveness of dioxidin in the local treatment of venous trophic ulcers in the inflammation stage with the effectiveness of modern antiseptic drugs based on the results of our previously conducted clinical studies (Table 3)
.
It turned out that in terms of the timing of cleansing and transition from the inflammation stage to the regeneration stage, the effectiveness of dioxidine is comparable to that of modern antiseptic drugs and is almost 2 times higher than the results of treatment in the control group, in which traditional solutions of chlorhexidine, miramistin, levomekol or levosin ointments were used.
Staphylococcus aureus in 60% of cases
, in 16% -
Proteus mirabilis
, in 10% -
Pseudomonas aeroginoza
(both in the form of a monoculture and in association with other microorganisms), the remaining 14% of patients have different associations of gram-positive and gram-negative microflora. At the end of treatment, all patients showed positive dynamics, non-pathogenic and opportunistic microflora were identified, not exceeding the critical level of contamination.
During cytological examination before treatment, the degenerative-inflammatory type of cytogram was determined in 70% of cases, inflammatory - in 20%, inflammatory-regenerative - in 10%. At the final visit, patients had a predominantly inflammatory-regenerative (57%) and regenerative-inflammatory (20%) type of cytogram.
There were no adverse events or complications during the treatment process. Only one patient experienced an allergic reaction in the form of local dermatitis during treatment, which was relieved with the use of local corticosteroid ointments.
All patients noted the ease of applying and removing bandages with dioxidine. Only 3 patients, due to old age, obesity, spinal osteochondrosis, and acute cerebrovascular accident, were forced to resort to the help of relatives during dressing changes. 3 patients, during dressings, noted a short-term burning sensation in the area of the ulcer, which disappeared within 0.5-1 hour and did not require discontinuation of treatment.
Thus, dioxidin is a broad-spectrum antibacterial drug that provides rapid cleansing of the wound surface from fibrin and pus, moisturizes the wound, reduces pain at the site of application, promotes rapid cleansing of the wound surface, stimulates regeneration and marginal epithelization. Its use in stage I of the wound process helps to reduce treatment time and transition to the granulation stage 3-4 days earlier compared to standard treatment. Along with this, due to the ease of use and low cost of the drug, patient adherence to this type of treatment was noted. This is extremely important, since many patients with venous trophic ulcers are treated on an outpatient basis and the simplicity-price-effectiveness ratio is one of the priorities in choosing a particular treatment method. The results of the study allow us to consider dioxidin, along with modern local antiseptic drugs, as an effective treatment for venous trophic ulcers in the first stage of the wound process and recommend it for wider implementation in the daily practice of phlebologists.
