RU2754383C1 - Method for treatment of uninfected postoperative wound defect of the foot in the absence of signs of critical limb ischemia in patients with neuropathic and neuroischemic forms of diabetic foot syndrome - Google Patents

Abstract

FIELD: medicine.SUBSTANCE: invention relates to the field of medicine, namely to surgery and endocrinology. In patients with deep uninfected postoperative wounds of the feet, without critical limb ischemia, intra-wound injections of rhEGF are performed in order to achieve faster filling of the wound bottom with granulations, followed by complete wound healing. Negative pressure therapy is also performed, which helps to improve the therapeutic prognosis and reduce the risk of limb amputation.EFFECT: accelerates the healing time of deep postoperative foot wounds in patients with neuropathic and neuroischemic forms of diabetic foot syndrome (DFS).1 cl, 2 ex

Description

Technology area

The invention relates to medicine, namely to surgery and endocrinology. The method is intended to accelerate the healing of deep postoperative wounds of the feet in patients with neuropathic and neuroischemic forms of diabetic foot syndrome (SDS).

State of the art

Diabetic foot syndrome (DFS) is one of the most frequently developing serious complications of diabetes mellitus, in which changes in the peripheral nervous system, arterial and microvasculature occur, which pose an immediate threat to the development of wound defects and gangrene of the foot. SDS is recorded in a quarter of patients with diabetes mellitus. This is the main reason for lower limb amputations in this category of patients.

According to domestic and foreign recommendations, the main principles of treating chronic wounds in DFS are: unloading the affected area of the foot; restoration of arterial blood flow; control of infection; control of diabetes and related diseases; local treatment of wounds, selected depending on the stage of the wound process, the severity of exudation, the dynamics of the state of the wound; teaching patients the rules of foot care; as well as relapse prevention.

Healing processes in persons with diabetes mellitus are slowed down, wound defects are prone to chronicity, and therefore the search for methods that accelerate repair at the cellular level is extremely urgent.

Even in the case when it is possible to avoid extensive surgical intervention on the foot, postoperative wounds have a complex structure, sawdust of bone fragments can remain in the bottom and, due to the deficiency of preserved soft tissues, it is impossible to perform plastic closure of the wound, which increases the risk of secondary infection, aggravates the effect of pain syndrome on the quality of life, and also leads to a huge investment of time for medical personnel and material resources.

Various methods of treating a deep, uninfected wound defect of the foot are known from the prior art.

The known method of covering shallow wound defects with hydrocolloid dressings, which promotes epithelialization by cleaning the wound, maintains a moist environment in the wound and reduces the risk of formation of rough scars. However, this method is not suitable for use on deep postoperative wounds due to the increased risk of secondary infection due to excessive exudation of deep wounds, and an excessive moist environment in the wound leads to maceration of the surrounding skin and an increase in the wound defect.

Alginate dressings are also used to treat deep wounds in diabetic foot syndrome. However, this method did not show a statistically significant difference in efficacy compared to other wound dressings such as spongy and hydrocolloid dressings. (Dumville JC, O'Meara S, Deshpande S, Speak K. Alginate dressings for healing diabetic foot ulcers. Cochrane Database of Systematic Reviews 2013, Issue 6. Art.No .: CD009110. DOI: 10.1002 / 14651858.CD009110.pub3. ).

Bioengineered skin is recognized as one of the progressive methods of wound closure. However, this method can only be used for superficial neuropathic wounds, and a small number of clinical studies dictate the need for further study of this technique. (Robert G. Frykberg and Jaminelli Banks.Advances in Wound Care.Sep 2015.560-582.http: //doi.org/10.1089/wound.2015.0635).

Recently, recombinant human growth factors have been used to treat diabetic foot syndrome.

The most studied molecule is epidermal growth factor. Recombinant human EGF has been shown to be effective in treating DFS (Robert G. Frykberg and Jaminelli Banks.Advances in Wound Care.Sep 2015.560-582.http: //doi.org/10.1089/wound.2015.0635). It has been registered and applied in the Russian Federation since 2014.

If standard treatments are not effective within four to six weeks, adjuvant therapy is recommended, which includes negative pressure therapy and growth factor drugs.

Epidermal growth factor (EGF) stimulates the migration of fibroblasts, endothelial cells to the ulcer, the formation of granulation tissue, angiogenesis, reduction of wound size with activation of myofibroblasts, migration and proliferation of epithelial cells. The effectiveness of treatment was, according to Cuban researchers, 69% compared with 18% in the control group of the studied patients.

In the Russian Federation, the drug rhEFR is registered (Eberprot P - 75 mg, HeberBiotec, Havana, Cuba). Clinical studies have shown that rhEGF accelerates the growth of epithelial, endothelial and fibroblast cells, tissue proliferation and cell chemotaxis; reduces the time until the ulcer defect is completely filled with granulation tissue, restores the normal functioning of tissues after damage (Berlanga J, Fernández JI, López E, López PA, del Río A, Valenzuela C, Baldomero J, Muzio V, Raíces M, Silva R, Acevedo BE , Herrera L. Heberprot-P: a novel product for treating advanced diabetic foot ulcer MEDICC Rev. 2013 Jan; 15 (1): 11-5. PubMed PMID: 23396236.). However, it is recommended to administer the drug 3 times a week.

In the study rchEFR efficiency at a dose of 75 .mu.g of complete wound healing was achieved at 20 weeks of observation (Fernández-Montequín, JI and all . ( 2007), Intralesional injections of Citoprot-P ® (recombinant human epidermal growth factor) in advanced diabetic foot ulcers with risk of amputation. International Wound Journal, 4: 333-343.doi: 10.1111 / j.1742-481X.2007.00344.x).

In the article by G.R. Galstyan. et al. presented a mathematical model for reducing the number of high amputations against the background of the use of rhEGF. However, the article indicates a number of limitations, namely, the calculation was based on the data of a retrospective analysis of the effectiveness of the drug on a foreign sample, which significantly reduces the reliability of the data in comparison with randomized clinical trials and cannot be extrapolated to the Russian population (Galstyan G.R., Ignatieva VI Avksentieva MV, Dedov II Clinical and economic analysis of the use of the drug epidermal growth factor (Eberprot-P ®) in patients with diabetic foot syndrome. Endocrine surgery No. 1 2013, pp. 4-15).

Considering the high cost of the drug and pain in the wound during the administration of the drug, this regimen is not always observed in real clinical practice.

In addition, the disadvantage is the lack of clear algorithms describing the protocol for the frequency and frequency of rhEGF injections. This can lead to tactical errors and unsatisfactory treatment results.

Thus, when rhEGF was used in the Russian population, wound defects (1.7 [0.9; 2.2] cm deep at the time of inclusion in the study) completely epithelized in 72% of cases within 12 weeks. In a control group comparable in terms of the characteristics of the state of wounds, which received standard treatment with atraumatic dressings, complete healing was achieved only in 48% of cases within 12 weeks. The differences obtained are statistically significant (p <0.01).

Negative pressure vacuum dressing therapy is a topical treatment that is also used to stimulate wound healing. This type of dressing with the provision of vacuum therapy is ideal for the treatment of profusely exudating wounds, facilitating the transition of the wound process from the inflammatory stage to the proliferative stage and the growth of granulation tissue. As a result of randomized clinical trials, it was proved that against the background of vacuum therapy, wounds in diabetic foot syndrome healed 1.4 times faster than standard treatment (Lavery L., Murdoch D., Kim P., Fontaine J., Thakral G., Davis K. Negative Pressure Wound Therapy With Low Pressure and Gauze Dressings to Treat Diabetic Foot Wounds. // Journal of Diabetes Science and Technology. - 2014. - Vol. 8. - No. 2. - P.346 - 349). However, with profusely exudating wounds, maceration of the edges of the skin is possible.

Disclosure of invention

The technical problem to be solved and the achieved technical result is a reduction in the healing time of foot wounds after performing the primary surgical treatment of the wound in patients with neuropathic and neuroischemic forms of DFS and improving the therapeutic and social prognosis.

This result is achieved when using a method for the treatment of uninfected postoperative wound foot defect in the absence of signs of critical limb ischemia in patients with neuropathic and neuroischemic forms of diabetic foot syndrome, including:

carrying out complex therapy, consisting of repeated cycles of exposure to the wound by intraraneous administration of recombinant human Epidermal Growth Factor (rhEGF) and subsequent application of a vacuum-assisted dressing (VAP) to the wound for 3 days with a negative pressure equal to 100-120 mm Hg,

the first cycle of exposure is carried out 24-48 hours after the initial surgical treatment,

in the event that after the first cycle of exposure, the area of the wound has decreased by 30% or more, then two additional cycles of exposure are carried out,

in the event that after the first cycle of exposure, the area of the wound has decreased by less than 30%, then four additional cycles of exposure are carried out.

For the treatment of wounds with an area of more than 10 cm ² , the rhEGF lyophilisate for injection is diluted in 5 ml of physiological solution, after which 5 injections of 1.0 ml are performed sequentially, while injections are carried out evenly distributing the injection of the drug over the wound, injecting first of all the edges of the wound, and then its bed, the depth of the needle insertion during the injection is about 0.5 cm.

The team of authors proposed and proved the significant effectiveness of the combination of the use of vacuum therapy and intraranial injections of rhEGF in the protocol described below in comparison with the existing methods separately.

According to Sheehan et al., 53% of patients who received standard therapy did not heal by 12 weeks. (Percent Change in Wound Area of Diabetic Foot Ulcers Over a 4-Week Period Is a Robust Predictor of Complete Healing in a 12-Week Prospective Trial Peter Sheehan, Peter Jones, Antonella Caselli, John M. Giurini, Aristidis Veves // Diabetes Care Jun 2003, 26 (6) 1879-1882; DOI: 10.2337 / diacare.26.6.1879).

When analyzing the rate of wound healing in patients who received only rhEGF therapy with comparable values of the area and depth of wounds at the start of local treatment, it was found that epithelialization of wounds was achieved on average within 12 weeks in 72% of patients (Zaitseva E.L., Tokmakova A .Yu., Zhilyaev VM, Galstyan GR Influence of recombinant human epidermal growth factor on wound healing in patients with neuropathic and neuroischemic forms of diabetic foot syndrome. // Diabetes mellitus, its complications and surgical infections. conferences with international participation. 2019).

The current study included patients (7 men, 8 women) with deep postoperative wounds of the feet, the median depth was 1.9 [0.8; 3.1] cm, the median area was 17.2 cm²... In the postoperative period, the patients used the method described above. treatment (a combination of negative pressure and rhEGF), the number of vacuum and rhEGF sessions varied from 3 to 5. Complete wound healing was achieved with the proposed technique in 83% of patients within 10 weeks. In the course of the study, a faster formation of granulation tissue was recorded, compared with standard therapy and therapy using only rhEGF. So, against the background of standard methods or each of the methods used separately, this result is achieved on days 7-14. Granulation tissue against the background of the proposed method filled the bottom of the wound 4-5 days after the surgical treatment of the wound. Thus, the authors concluded that the claimed method is optimal for achieving successful epithelialization.

When analyzing the data obtained to achieve complete epithelialization by week 10, the correlation was studied between the percentage of wound area reduction (healing rate), the number of injections performed, the number of cycles of rhEGF and vacuum-assisted dressing, depending on the percentage of wound area reduction after the first treatment cycle.

For research, the patients were divided into groups: the first group included patients (healers) who were treated with the claimed method, and who, as a result of the treatment, achieved complete healing by week 10; the second group included patients who were treated according to a scheme different from the claimed one, while this group was divided into two subgroups, where in one subgroup two additional cycles of exposure were carried out with a reduction in the wound area by 20%, and four cycles of exposure with a reduction in the area wounds by less than 20%; in the second subgroup, the threshold of the wound area of 30% was used as a criterion for changing the number of treatment cycles, while a different number of exposure cycles was used - one and four additional effects with a reduction in the wound area of more than 30% after applying the first cycle, and two additional effects in the case of reduction of wound area less than 30% after application of the first cycle. Patients in the second group did not show wound healing by week 10 (non-healers).

In particular, in some of the patients of the healers group, in whom wound reduction by 30% or more occurred after one cycle of rhEGF and vacuum therapy, after 2 injections of rhEGF and 2 sessions of vacuum therapy, complete epithelialization was achieved by 10 weeks. In the rest of the patients in this group, who did not achieve a reduction in wound size by 30% after the first cycle of vacuum therapy and 1 injection of rhEGF, an additional 4 cycles of vacuum therapy and rhEGF were performed. After 10 weeks, patients demonstrated complete wound epithelialization.

An analysis of non-healers subgroups revealed that with less than 30% wound reduction after 1 session and an additional 2 rhEGF injections in combination with 2 vacuum therapy sessions, patients achieved complete epithelialization only by 16 weeks of treatment. Patients with a satisfactory healing rate - more than 30%, who after 1 cycle underwent only one additional cycle of vacuum therapy and rhEFR, achieved complete epithelialization only by 14 weeks of treatment, and the implementation of additional 4 cycles of vacuum therapy and rhEFR after 1 cycle led to to excessive growth of granulations - these patients did not achieve healing by week 10 due to the presence of hypergranulations that interfere with adequate epithelialization.

The results obtained suggest an increase in the effectiveness of treatment by the claimed method of an uninfected postoperative wound defect of the foot in the absence of signs of critical limb ischemia in patients with neuropathic and neuroischemic forms of diabetic foot syndrome in comparison with known methods.

In addition, the authors showed the prognostic value of assessing the dynamics of healing after using 1 injection of rhEGF and 1 session of vacuum therapy. In the case of a wound reduction of 30% or more, patients needed fewer injections of the drug. Patients who did not achieve this indicator required more rhEGF injections and vacuum sessions.

The literature describes individual methods of treatment using vacuum therapy and rhEGF, however, the study included patients with wound defects of various origins (post-traumatic, venous, diabetic, electrical injury), as well as various localization (legs, feet, hands), which contradicts the indications for the use of epidermal growth factor. In addition, the course of the wound process against the background of various pathologies differs significantly, and it seems not entirely legitimate to randomize both persons with diabetes and persons without diabetes into one group (Tan, L., Hou, Z., Gao, Y. "Efficacy of combined treatment with vacuum sealing drainage and recombinant human epidermal growth factor for refractory wounds in the extremities and its effect on serum levels of IL-6, TNF-α and IL-2. "Experimental and Therapeutic Medicine 15.1 (2018): 288-294) ...

In traditional negative pressure therapy, the limiting factor is the presence of a bone fragment in the bottom of the wound, and the presence of osteomyelitis is a contraindication to the use of this method of local treatment.

On the contrary, for the claimed method of treatment, the presence of a bone fragment in the bottom of the wound is not a limitation due to the rapid growth of granulations against the background of rhEGF injections (the drug is injected into soft tissues, the bone is intact).

Implementation of the invention

The proposed method is as follows: in patients with deep and structurally complex uninfected wounds, in the absence of critical limb ischemia, in 24-48 hours after the surgical treatment, rhEGF is injected (Eberprot P). The contents of each vial with the RFEFR preparation are reconstituted by adding 5 ml of solution for injection to it. The syringe should be equipped with a 26Gx1 / 2 "needle or a 24Gx1 1/2" needle for intramuscular injections.

For the treatment of wounds with an area of more than 10 cm ² , ten injections of 1.0 ml are made. Injections are made into soft tissues with a uniform distribution of the injection sites, first of all, by chipping the edges of the wound, and then the wound bed. The depth of insertion of the needle during injections is about 0.5 cm. The needle should be changed before each intraran injection to avoid infection.

The criterion for determining the tactics of treatment was chosen to reduce the size of the wound by 30% or more. The algorithm for determining this indicator is described above.

The area of the wound is determined by a planimetric method by tracing the contours of the wound through a transparent scale film (Opsite Flexgrid, Smith and Nephew, UK) and then counting the number of square centimeters within the contour. The depth of the wound defect was assessed using a sterile ruler.

On the third day after administration of the drug, a vacuum-assisted bandage was applied to the wound for 3 days. The negative pressure therapy system consists of three components: a vacuum device with a disposable canister and associated tubing, a sterile polyurethane sponge or cotton gauze tailored to the size of the wound, and a sealing film. The magnitude of the pressure is from 100 to 120 mm Hg. (depending on the condition of the wound defect and the severity of the possible pain syndrome). In the presence of a neuropathic defect, abundant exudation, the value of negative pressure can be 120 mm Hg. In the presence of a neuroischemic wound (strictly in the absence of signs of critical ischemia) and pain during negative pressure therapy, the recommended negative pressure value is 100 mm Hg.

The number of sessions depends on the dynamics of the state of the wound defect.

Re-introduction of rhEGF can be performed immediately after removing the vacuum-assisted dressing with subsequent reproduction of the algorithm described above. In order to avoid the growth of hypergranulations, and, as a consequence, the slowing down of epithelialization due to the difficulty in the migration of keratinocytes, it is recommended to subsequently switch to standard therapy with atraumatic dressings recommended for use on epithelializing wounds, Wagner I.

The use of a therapeutic complex of rhEGF and a vacuum-assisted dressing (VAP) according to a certain scheme promotes the activation of various links of reparative processes: a cascade of synthesis of growth factors is launched, which, in turn, stimulates the proliferation of fibroblasts, keratinocytes, endothelial cells aimed at the growth of newly formed vessels, there is an immediate removal of pro-inflammatory cytokines and enzymes that destroy collagen (matrix metalloproteases). At the same time, a decrease in periranial edema leads to the formation of healthy high-quality granulation tissue, which can significantly reduce the time of wound healing, improving the therapeutic prognosis and reducing the risk of amputation of the affected limb.

The inventive method does not require specific preparation, reduces the risk of additional tissue trauma and secondary infection when changing dressings, which does not disrupt the healing process and shortens the patient's stay in the hospital. In addition, the claimed method will significantly reduce the cost of treatment and will help specialists of various specialties to unify the approach to the application of these methods of local treatment.

As a result of earlier studies, the developed method made it possible to increase the rate of wound healing, to reduce the time of active inpatient treatment of patients with deep neuropathic and neuroischemic wound defects on the background of diabetes mellitus.

Clinical example 1.

Patient L., 62 years old, was hospitalized in the department of diabetic foot from 16.10.18 to 16.11.18 with a clinical diagnosis of type 2 diabetes mellitus. Distal diabetic polyneuropathy. Obliterating atherosclerosis of the arteries of the lower extremities. KHAN 3a. Diabetic foot syndrome, neuroischemic form. Condition after amputation of 2 toes of the right foot with the head of the metatarsal bone from 28.09.2018. IHD: Postinfarction cardiosclerosis after AMI in 2016. Essential hypertension II, stage AH 3, risk of CVC 3. Hypercholesterolemia. Common atherosclerosis. CHF BAP with VTK stenting on 03/30/2016, PMZhV and BAP DV on 04/20/2016, PKA and BAP ZBV, PMZHA, IV on 07.21.2016, PMZHV on 02/20/18, balloon vasodilation with RCA stenting on 1.06.18. Multinodular goiter, euthyroidism. Bilateral gonoarthrosis, X-ray stage 2, Duodenal ulcer in remission, Doubling of the left kidney.

Local status at admission: Right foot: condition after amputation of 2 toes with the metatarsal head. The postoperative wound is 5x2 cm, the depth of the wound is 3 cm, in the bottom there are flaccid granulations covered with dense fibrin. There is hyperemia of the tissues surrounding the wound, edema up to the level of the upper third of the leg. The blood flow through the arteries of the right foot and lower leg is preserved. Tactile and vibration sensitivity is absent below sr / 3 of the lower leg.

Surgical treatment was performed in the amount of: Amputation of the 3rd toe of the right foot with resection of the metatarsal head. The postoperative period was uneventful. The wound was managed in an open manner.

Plastic wound closure was impossible due to the localization of the postoperative defect and soft tissue deficiency.

There were daily dressings of the postoperative wound, antibacterial therapy (Cefotaxime 1.0 2 times a day), unloading of the lower limb using a wheelchair. During examinations, data on the presence of critical ischemia were not obtained, transcutaneous oximetry - 38-45 mm Hg. This made it possible to continue the treatment of the wound according to the developed method.

The size of the postoperative wound was 6x2.5 cm (wound area - 15 cm ² ), the depth of the wound was 5 cm without signs of inflammation and infection.

48 hours after the surgical treatment of the wound, the first cycle of actions was started.

Since 20.10.2018, the department has initiated intraraneous injections of recombinant human epidermal growth factor 75 μg + water for injection 5 ml. The syringe was equipped with a 24Gx1 1/2 "needle for intramuscular injections.

Injections were performed into soft tissues with a uniform distribution of the injection sites, chipping the edges and then the wound bed. The depth of needle insertion during injections was about 0.5 cm. The needle was changed before each injection.

On 10/23/19, a vacuum-assisted bandage was applied to the wound for 72 hours (3 days). The negative pressure therapy system consisted of three components: a vacuum device with a disposable canister and associated tubing, a sterile polyurethane sponge or cotton gauze matched to the wound, and a sealing film (Hartmann, Germany or Smith & Nephew, UK). The pressure was -100 mm Hg. due to pain syndrome.

On 10/26/2018, the vacuum-assisted dressing was removed.

According to the evaluation, the size of the wound was 5.5 x 2.1 cm (area 12 cm ² ). Thus, the size of the wound was reduced by 20%, which made it possible to determine the algorithm for further treatment: it was required to perform 2 more cycles of vacuum + rhEGF.

An injection of 5 ml of rhEGF was performed according to the scheme described above.

On October 29, 2018, a vacuum-assisted bandage was reapplied for 72 hours (3 days).

In total, the method described above was carried out 3 injections of rhEGF and 3 sessions of vacuum therapy according to the proposed method.

On 15 November 2018, the vacuum-assisted dressing was removed. The bottom of the wound defect is completely covered with granulation tissue. The depth of the defect was 0.5 cm, and the size of the wound was 1x1.5 cm.

The patient was discharged on November 16, 2018 for outpatient treatment; the use of atraumatic dressings was recommended.

At the follow-up visit on December 26, 2018, the depth of the wound was 0.3 cm, the size was 0.6x1 cm; on December 15, 2018 (at the 9th week), during the control examination, the wound defect was completely epithelized. During the next year, no recurrence of wounds was recorded.

The chosen method of treatment made it possible to achieve timely healing of the wound defect, which led to a reduction in the total treatment time of the patient. The result of the complex treatment was the preserved support function of the limb.

Clinical example 2.

Patient V., 74 years old, was hospitalized in the diabetic foot department from 03/06/16 to 04/16/16 with a clinical diagnosis of type 2 diabetes mellitus. Distal diabetic polyneuropathy. Obliterating atherosclerosis of the arteries of the lower extremities. KHAN 3a. Diabetic foot syndrome, neuroischemic form. Condition after opening the phlegmon and surgical treatment of the left foot wound dated 03/10/2016. Condition after balloon angioplasty of the left leg arteries from 17.02.2016.

Local status: Left foot: normal color and moisture. On the plantar surface there are 2 postoperative wound defects, communicating with each other, without signs of infection and inflammation. At the bottom, sluggish granulation. The blood flow through the arteries of the right foot and lower leg is preserved. Tactile and vibration sensitivity is absent below sr / 3 of the lower leg.

Surgical treatment was carried out in the amount of: opening the phlegmon and surgical debridement of the left foot wound. The postoperative period was uneventful. The wound was managed in an open manner.

Plastic wound closure was impossible due to the localization of the postoperative defect and soft tissue deficiency.

There were daily dressings of the postoperative wound, antibacterial therapy (Meronem 1.0 2 times a day), unloading of the lower limb using a wheelchair. During examinations, data on the presence of critical ischemia were not obtained, transcutaneous oximetry was 40 mm Hg. This made it possible to continue healing the wound with negative pressure therapy.

The size of the postoperative wound was 15x8 cm (wound area - 90 cm ² ), the depth of the wound was 5 cm without signs of inflammation and infection. 24 hours after the surgical treatment of the wound, the first cycle of interventions began. Since 03/15/2016, vacuum therapy of the wound has been initiated in the department. The negative pressure therapy system consisted of three components: a vacuum device with a disposable canister and associated tubing, a sterile polyurethane sponge or cotton gauze tailored to the size of the wound, and a sealing film (Smith & Nephew, UK). The pressure was -100 mm Hg. due to the neuroischemic form of diabetic foot syndrome.

^On March 18, 2016, the vacuum-assisted dressing was removed, the wound area was 85.4 cm 2 (size - 14x6.4 cm), the healing dynamics was 5.2%. The vacuum-assisted dressing was reapplied for 72 hours (3 days).

By the method described above, 4 sessions of vacuum therapy and RFEGF injections were carried out.

By the end of the treatment, the wound defect had decreased in size, the granulation formed a “wall” inside, forming 2 wound defects. The bottom of the wounds is completely covered with granulation tissue. The depth of both defects was 0.5 cm, the size of the wounds was 5x6 and 4x8 cm, respectively. Further, dressings were carried out with atraumatic dressings. Later, the patient was discharged from the hospital on 04/16/2016 for outpatient treatment.

Thus, the proposed method makes it possible to shorten the healing time of extensive postoperative wounds of the feet in patients with diabetes mellitus, which significantly reduces the risk of secondary infection, and also reduces the time of work of medical personnel and the cost of additional dressings. This method can significantly reduce the risk of amputation of the affected limb in a patient with diabetes mellitus.

In addition, the proposed method requires fewer rhEGF injections (about 3-5), which is extremely important for both the patient and health care, given its high cost.

Claims (2)

1. A method for the treatment of uninfected postoperative wound foot defect in the absence of signs of critical limb ischemia in patients with neuropathic and neuroischemic forms of diabetic foot syndrome, including a complex therapy consisting of repeated cycles of exposure to the wound by intraraneous administration of recombinant human epidermal growth factor (rhEGF) and subsequent applying a vacuum-assisted dressing (VAP) to the wound for 3 days with a negative pressure equal to 100-120 mm Hg, the first cycle of exposure is carried out 24-48 hours after the initial surgical treatment; in the event that after the first cycle of exposure the area of the wound has decreased by 30% or more, then two additional cycles of exposure are carried out, if after the first cycle of exposure the area of the wound has decreased by less than 30%, then four additional cycles of exposure are carried out. 2. The method according to claim 1, characterized in that for the treatment of wounds with an area of more than 10 cm ² , the rhEGF lyophilisate for injection is diluted in 5 ml of physiological solution, after which 5 injections of 1.0 ml are performed sequentially, while the injections are evenly distributed along the wound, the introduction of the drug, injecting first of all the edges of the wound, and then its bed, the depth of the needle insertion during injections is about 0.5 cm.