RU2752747C1 - Method for treating trophic skin disorders in patients with severe brain damage - Google Patents

Abstract

FIELD: medicine.SUBSTANCE: invention relates to medicine, namely to surgery and neurology, and concerns treatment of trophic skin disorders in patients with severe brain damage. Therefor, poor and platelet-enriched autologous plasma is sequentially introduced. The plasma is introduced subcutaneously in a volume of 0.2 ml per injection into the edges along the perimeter of the area of the trophic skin disorder at an interval of 2 to 3 mm, followed by application of autologous plasma to the entire surface of the trophic skin disorder, corresponding to the one currently administered in form of injections. 2 to 3 procedures are performed at an interval of 7 days for each autologous plasma.EFFECT: method ensures effective treatment of trophic skin disorders in patients with severe brain damage due to delivery of a plastic material to the damaged area for active proliferation and stimulation of inherent regenerative processes.1 cl, 2 dwg, 1 ex

Description

The invention relates to medicine, namely to surgery, anesthesiology, resuscitation, neurology and biomedicine, and can be used in the treatment of trophic disorders of the skin in patients with severe brain damage of various origins, accompanied by neurodystrophic syndrome.

The cause of the occurrence of trophic skin disorders in patients with neurological deficit is a violation of microcirculation, mainly in the areas of the patient's body that are in contact with the bed. In patients with severe brain damage (traumatic, post-hypoxic genesis, with the consequences of intracranial hemorrhages, dislocation syndrome), the occurrence of pressure ulcers is also facilitated by the development of neurodystrophic syndrome, and the rapid development of trophic disorders of the skin and mucous membranes. The predominance of catabolic processes and their insufficient drug correction leads to hypoproteintemia, hypoalbuminemia, which also contributes to the occurrence and is the cause of long-term healing of trophic skin lesions. In patients with severe brain damage, neurodystrophic changes in connective tissue with discharging and thinning of connective tissue structures can clinically manifest as the formation of skin defects even with a slight and short exposure to pressure. The process of tissue restoration in the decubitus area is lengthy, in most cases, a long course of the local inflammatory process and an insufficiency of regenerative processes for epithelialization and scarring are observed.

A known method of treating trophic skin disorders (RF patent No. 2197290 from 2004), including autodermotransplantation and electrophoresis of 0.1% xymedon solution. Electrophoresis of the donor site is carried out 3-4 days before autodermoplasty and after it for 7-8 days.

A known method for the treatment of trophic skin disorders (RF patent No. 2450833 from 2010), which consists in the use of a biologically active dressing, which is an artificial carrier "SUPROSORB X" with included in its structure of living cells fibroblasts.

There is also known a method of treating trophic skin disorders (RF patent No. 2661084 of 2018), in which a complex effect on pressure ulcers is carried out, including daily surgical treatment in conjunction with laser exposure. Laser exposure is carried out by contact on the adjacent tissues in 4-6 zones and directly on the entire area of the ulcer in 2-3 zones with an exposure of 1-2 minutes per zone.

The disadvantages of these methods are: the need to use surgical methods of treatment, the use of drugs that can cause side effects and allergic reactions, the need to use additional equipment (laser).

Closest to the claimed is a method of treating trophic skin disorders (Prosyannikova N.V., Lipova E.V., Pokrovsky K.A., Tarasenko G.N. Modern methods of treating long-term non-healing skin wounds. "Russian Journal of Skin and Venereal Diseases" No. 6, 2012, p. 47-510), taken as a prototype. Autologous platelet-rich plasma is used in the form of injections (20 injections of 0.1 ml each) into the edges along the perimeter of the wound, as well as in the form of an application on the entire surface of the ulcer in the form of a fibrin film. To prepare a fibrin film, calcium chloride is added to a test tube with plasma in the following ratio: 1 ml of plasma - 50 μl of calcium chloride and mix thoroughly. Then the plasma is poured into a Petri dish and placed in a thermostat with a temperature of 37 ° C until a fibrin film is formed. Autologous plasma is used once, then every 2 days, dressings are carried out with a 1% solution of iodopyrone. The duration of treatment is 12 weeks.

However, the prototype is not effective enough due to the following factors: the reparative capabilities of tissues in the area of trophic skin disorders are limited due to the lack of plastic material; a single use of autologous plasma provides an unstable effect; the presence of wound exudate. In case of trophic skin disorders in patients with neurodystrophic syndrome, local immunity mechanisms are disturbed, there is not enough plastic material in the wound for active proliferative processes, secondary tissue alteration occurs, supported by the cells of the focus itself, and mononuclear infiltration is characteristic.

The invention is aimed at creating a method for treating trophic skin disorders in patients with severe brain damage, providing an increase in the effectiveness of treatment by stimulating their own regenerative processes when using autologous platelet plasma.

The specified technical result in the implementation of the invention is achieved by the fact that in a method for the treatment of trophic skin disorders in patients with severe brain damage, including the use of autologous plasma enriched with platelets, in the form of injections into the edges along the perimeter of the wound, and applications on the entire surface of the trophic skin disorder, carry out sequential combined use of autologous plasma: poor and rich in platelets, by introducing subcutaneous injections in a volume of 0.2 ml. into the edges along the perimeter of the trophic skin disorder site, with an interval of 2-3 mm, followed by applying autologous plasma to the entire surface of the trophic skin disorder corresponding to the plasma injection at the moment, 2-3 procedures are performed with an interval of 7 days of each autologous plasma.

In patients with manifestations of neurodystrophic syndrome, a staged approach to the local treatment of trophic lesions of soft tissues is required. Autologous plasma contains, in addition to platelets, amino acids, minerals, vitamins. In this regard, it seems expedient to use platelet-poor plasma at the first stage of treatment. At the next stage, when the wound is "saturated" with plastic material, platelet-rich plasma is used. The advantage of using platelet-rich plasma is the introduction of growth factors directly into the wound area, which helps to restore metabolic processes, local neoangiogenesis, improve metabolism in cells, and activate local immunity.

Platelet autoplasma modulates and regulates the function of primary, secondary and tertiary growth factors, affects all stages of regeneration at the same time. Growth factors are delivered to the tissues during the injection form of autoplasma and are concentrated by introducing a larger amount of plasma - this increases the activity of fibroblasts (connective tissue cells) and stimulates their formation. Fibroblasts, in turn, synthesize collagen, hyaluronic acid and elastin. This process leads to the formation of young connective tissue, the growth of capillaries. By launching all the links of natural regeneration processes and enhancing their action, autologous platelet plasma is a convenient and safe biological "tool" that accelerates regenerative processes. Autoplasm itself is natural for the individual patient's own tissues, it is not toxic and is not immunoreactive.

The method is carried out as follows.

Venous blood is taken from a patient with a volume of 15-20 ml, depending on the area of the trophic skin disorder. Blood sampling is performed in 3-4 sterile 5 ml tubes with sodium citrate or ACD-A. The tubes are placed in a centrifuge, blood is centrifuged for 5 minutes with parameters corresponding to 1000 G (RCF - Relative centrifugal force, relative centrifugal acceleration) to obtain platelet-poor plasma. After centrifugation, autologous platelet plasma is taken with a syringe, which is located in the upper part of the tube. Immediately before the injection of autologous plasma, the wound is washed with an antiseptic solution (prontosan or chlorhexidine). The manipulation is performed under sterile conditions. Autologous plasma injections are performed with a needle for subcutaneous injections into the edges along the perimeter of the trophic skin lesion site through 2-3 mm with a volume of 0.2 ml, depending on the area of the trophic lesion. Then the plasma corresponding to the currently injected plasma is applied directly to the surface of the trophic skin disorder by the application method, or a gauze swab soaked in plasma is placed in the wound. After completing the procedure, a sterile sticker is applied to the wound. The procedures are performed with an interval of 7 days 2-3 times and are combined with standard dressings with antiseptic solutions, wound healing ointments. Then, 7 days after the last injection, venous blood is taken from a patient with a volume of 15-20 ml in 3-4 sterile 5 ml vacutainers with sodium citrate or ACD-A. The tubes are placed in a centrifuge, blood is centrifuged for 5 minutes, with centrifugation parameters corresponding to 500 G, to obtain platelet-rich plasma. Plasma is taken directly above the "Buffy Coat" - the line of the limiting concentration of platelets and erythrocytes. Injections are made in a volume of 0.1-0.2 ml into the edges along the perimeter of the trophic skin damage area every 2-3 mm. Then the plasma is applied directly to the entire wound surface. Injections are performed with an interval of 7 days 2-3 times. The number of injections depends on the characteristics of the wound, the patient's condition: if the patient has hypoalbuminemia, hypoproteinemia, and the area of trophic lesion is clearly poor in plastic material, then we make 3 injections of plasma, poor in platelets. And, accordingly, depending on the dynamics of wound healing, we introduce 2 or 3 injections of platelet-rich plasma.

The inventive method was developed and passed clinical trials in the treatment of 11 patients with severe brain damage and long-term impairment of consciousness on the basis of the department of anesthesiology and resuscitation of the N.N. A.L. Polenov (a branch of the VA Almazov National Medical Research Center), as well as on the basis of the intensive care unit for neurosurgical patients of the St. Petersburg State Budgetary Institution of Health "City Mariinsky Hospital". The bedsores of the following localization were treated: in the sacral region - in 8 patients, the occipital region - in 1 patient, non-healing wound of the tracheostomy tract - in 2 patients. The etiology of brain damage was the consequences of traumatic brain injury (TBI) in 6 patients, the consequence of hypoxia - 5 patients. The duration of trophic skin disorders was: in 5 patients - more than 4 weeks, in 4 patients - more than 8 weeks, in 2 patients - more than 12 weeks. Three patients had second-degree bedsores and eight had third-degree bedsores. The area of the wounds ranged from 15 to 30 cm ² . Microbiological characteristics of wounds: when sowing the discharge from wounds, three patients showed the growth of Proteus mirabilis, two - Klebsiella pneumonia, one - Pseudomonas auroginosa, and one - a combination of Proteus mirabilis and Pseudomonas auroginosa growth, and one - a combination of Proteus mirabilis and Klebsiella pneumonia growth ... In the presence of indications for the systemic administration of antibiotic therapy, data on the sensitivity of the flora to antibiotics were taken into account when choosing antibiotic therapy. All patients were prescribed therapy for the underlying disease and local treatment aimed at cleansing and decontaminating the wound, which led to a decrease in inflammation, but did not contribute to sufficient wound regeneration. The use of poor and platelet-rich autologous plasma made it possible to accelerate the processes of regeneration and epithelialization of wounds.

The inventive method is confirmed by a clinical example, which is illustrated by photographs, where:

in fig. 1 and FIG. 2 shows pictures of the histological specimen of the edge of the pressure ulcer before the start of treatment and after the treatment, respectively.

Example.

Patient I., 56 years old. Diagnosis: S06.31 Focal brain injury with open intracranial injury. Severe brain contusion. Contusion foci of the temporal, frontal lobes, left hemisphere of the cerebellum. SAK. Intraventricular hemorrhage. Fractures of the base of the skull in the middle cranial fossa, left mastoid process. Closed chest injury. Decubitus in the region of the sacrum of the 3rd degree.

The patient was admitted to the department on the 30th day after the injury by transfer from the city multi-line hospital. At the time of admission, the assessment on the FOUR SCORE scale: E1 R2 M2 V2. The level of consciousness is a state of minimal consciousness "minus" - the patient fixes his gaze, but does not perform the proposed tasks. Breathing through a tracheostomy, independent, adequate. Hemodynamics are stable. Pupils d≥s, photoraction on the right is extremely sluggish, corneal reflexes are vivid. It fixes the gaze to a mirror and a bright ball, a protective blinking reflex and an orientation reaction to sound are triggered. Lies mostly with closed eyes, opens gaze to pain. Localizes pain with the left hand. Deep reflexes are extremely low, polyneuropathy of critical conditions is noted. According to laboratory data, hypoproteinemia, signs of a systemic inflammatory reaction. In the region of the sacrum - a pressure ulcer of 3 degrees, an area of 5.0 × 10.0 cm, with uneven edges, a bottom with fibrin overlays, in the center - necrosis with an area of 3.0 × 5.0 cm, along the edges of the wound - perifocal inflammation, granulation flaccid ... Serous discharge from the wound, scanty. When sowing the discharge, microbes are sown: Klebsiella pneumonia and Proteus mirabilis. A necrectomy was performed. A diagnostic biopsy was taken from the edge of the pressure ulcer. Histological description of the preparation from a pressure ulcer (before the start of therapy): granulation tissue with a large number of vessels, impaired formation of layers; the stroma is loose, with varying degrees of collagenization; wide leukocyte-necrotic surface layer, edematous changes; severe diffuse stromal and perivascular infiltration with neutrophilic leukocytes. Fragments of the epidermis are missing. Conclusion - a picture of non-healing chronic pressure ulcer, represented by granulation tissue with diffuse chronic inflammation of pronounced activity. FIG. 1 shows a histological preparation of the edge of a pressure ulcer before treatment with autologous plasma. Inflammatory infiltration in granulation tissue, mild fibroplasty.

According to the claimed method, autologous plasma injections were carried out four times during the period of hospitalization with an interval of 7 days: twice were injections of platelet-poor plasma, twice injections of platelet-rich plasma. Against the background of the treatment, the size of the bedsore decreased approximately two times, its area was 3.0 × 5.0 cm, the signs of inflammation regressed, the area of granulations increased, and the appearance of epithelialization along the periphery was noted. When re-sowing from the surface of the wound, there is no growth of flora. A diagnostic biopsy was performed from the edge of the pressure ulcer.

Histological description of the drug from the bedsore (after the course of treatment, on the 27th day of hospitalization in the department): granulation tissue with moderate fibroplasty, thickened fibers, crimped. The surface layer is represented by a fibrinous film (scab). Weak stromal infiltration with leukocytes, plasma cells, limited to the surface layers. Fragments of the epidermis. Conclusion - a picture of a chronic pressure ulcer, represented by granulation tissue with superficial chronic inflammation of weak activity and the beginning of epithelialization. When compared with the primary biopsy, there is a decrease in inflammatory infiltration, collagenization of granulation tissue, and marginal epithelization. FIG. 2 shows a histological preparation of the edge of a pressure ulcer after a four-time injection of autologous blood plasma. The absence of inflammatory infiltration in the maturing connective tissue, focal collagenization, a decrease in the number of vessels.

Thus, the use of the proposed method for the treatment of trophic skin disorders in patients with severe brain damage made it possible to increase the effectiveness of the treatment of patients with trophic skin lesions due to:

- improving the results of the treatment of trophic skin lesions in the form of accelerating the development of regeneration and epithelialization processes;

- reduction of the terms of treatment of trophic skin lesions in patients with severe damage to the central nervous system (CNS).

The proposed method can be used both as monotherapy and in combination with other methods of treating trophic skin lesions.

The applicant asks to consider the submitted materials of the application "Method for the treatment of trophic skin disorders in patients with severe brain damage" for the issue of a RF patent for an invention.

Claims (1)

A method of treating trophic skin disorders in patients with severe brain damage, including the use of autologous platelet-rich plasma in the form of injections into the edges along the perimeter of the wound and applications on the entire surface of a trophic skin disorder, characterized in that sequential combined use of autologous plasma, poor and platelet-rich, by introducing subcutaneous injections in a volume of 0.2 ml into the edges along the perimeter of the trophic skin disorder site, with an interval of 2-3 mm, followed by applying autologous plasma to the entire surface of the trophic skin disorder, corresponding to the currently injected plasma injection, 2-3 procedures are carried out with an interval of 7 days for each autologous plasma.

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