Stimulation of Wound Healing and Prevention of Purulent-Necrotic Complications After Lower Extremity Amputations in Patients with Diabetes Mellitus

The research is dedicated to the development and implementation of a method for stimulating wound healing and preventing purulent-necrotic complications after high amputations of the lower extremities in patients with diabetes mellitus complicated by gangrene of the foot. Low-intensity laser irradiation and modern medications with antioxidant properties (mexidol, serotonin adipinate, plant-origin polyantioxidants) were used. The obtained data demonstrate the effectiveness of the developed method, which allows reducing postoperative mortality, decreasing the number of wound healing complications, and shortening the treatment duration.

Relevance of the Research.

According to WHO data, at present more than 120 million people in the world suffer from diabetes mellitus, and every 12-15 years this number doubles (5, 10, 46, 50, 113, 174). In Russia in 2000 approximately 3 million patients with diabetes mellitus were registered, and by 2010 their number is projected to increase to 7 million and more (16, 18, 44, 62, 111, 132, 141, 160). The most frequent complication of diabetes mellitus is the development of purulent-necrotic lesions of the lower extremities (6, 7, 8, 12, 17, 18, 23, 80, 92, 110, 116, 139, 168, 175). The high predisposition of diabetes mellitus patients to the development of purulent-necrotic lesions of the lower extremities is conditioned by a symptom complex of anatomo-functional changes associated with diabetic micro- and macroangiopathy, neuropathy, and osteoarthropathy, which have received the name - diabetic foot syndrome (5, 10, 11, 111, 141, 155, etc.). This symptom complex is a consequence of the integral process of adaptive restructuring of the endocrine-metabolic status in the direction of disadaptation: formation of metabolic syndrome, increased activity of the sympatho-adrenal system, glucocorticoid activity, alteration of carbohydrate and lipid metabolism activity, suppression of the organism's natural resistance (5, 6, 7, 9, 12, 23, 26, 46, 80, 113, 124, 142, 150, 152, 169, 171).

However, paradoxically but factually, correction of metabolism, strict control of glycemia, and the use of various means and methods affecting the normalization of microcirculation have not exerted a noticeable influence on the prevention of the development of purulent-necrotic complications in this category of patients whatsoever, and especially after performed amputations of the extremities (39, 44, 62, 65, 69, 80, 85, 104, 107, 123, 160, 168, etc.). The use of antibacterial preparations did not justify expectations with respect to the prevention of purulent-necrotic complications and stimulation of healing of postoperative wounds (92, 112, 114, etc.).

According to existing concepts, prophylactic use of antibiotics slows the clinical manifestations of purulent processes and may contribute to impaired wound healing, which often is not accompanied by an expressed temperature reaction and changes in blood indicators, that substantially complicates diagnosis and treatment of patients (30, 37, 52, 63, 64, 73, 91, 112, etc.). Moreover, many researchers have noted a decrease in the general immunological resistance of the organism under the influence of antibiotic therapy (10, 43, 62, 107, 114, 124), which entails an increase in the percentage of postoperative wound purulent complications in patients with diabetes mellitus (14, 73, 91, 134).

Other methods available to clinicians for the prevention of wound healing disorders after amputation of an extremity, such as impact on the wound process through the use of a pulsating stream of antiseptic solution (37, 73, 113.), ultrasonic wound processing, ozone therapy, NO-therapy (2, 54, 72, 85, 132), as well as impact with a CO2-laser beam (119) for the prevention of purulent complications after amputation of extremities, are currently not applied.

In the literature there are sufficiently convincing data indicating that low-intensity laser irradiation substantially improves wound healing conditions, leading to a decrease in postoperative complications and a shortening of the duration of postoperative treatment (4, 28, 29, 53, 70, 78, 86, 104, 119, 126, 138, 165).

Wound healing, by modern concepts, is a coordinated process passing through certain stages with the participation of various cells and products of their activity regulating the healing process (122, 132). The wound healing process can with full justification be attributed to so-called 'free radical pathologies' (30, 83, 123, 125, 133, 160), characterized by the activation of free radical reactions (FRR) (158). In the process of wound healing, inactivation of a balanced system of endogenous FRR inhibitors is observed, as a result of which the normal succession of wound process stages is delayed and the rate of wound healing slows down (123, 125, 177). A decrease in the activity level of the endogenous antioxidant defense system against the damaging action of FRR constitutes the pathogenetic justification for the use of various exogenous FRR inhibitors as wound healing stimulants.

One of such preparations for the prevention of purulent postoperative complications is mexidol - a synthetic hydrophilic antioxidant (81, 83). According to available data, the antioxidant mexidol removes oxidative stress in damaged tissues, decreases inflammatory manifestations, including microcirculation disorders, and also exerts a membrane-protective action (122, 125). In modern literature there are also reports on the good therapeutic effect of the plant-origin polyantioxidant ADF-37, administered 'per os' and accelerating the healing of aseptic wounds after laparotomy (17).

A new direction in the treatment of diabetic foot syndrome in recent years has been the use of serotonin adipinate. It is known that serotonin adipinate participates in the realization of a number of important physiological functions of the organism: transmission of nerve impulses, regulation of gastrointestinal motility, hemostasis, and vascular reactions. Under different conditions it is capable of manifesting both vasoconstrictor and vasodilator action, which in itself may substantially influence the wound process. In recent years, a number of authors have regarded serotonin adipinate as an antioxidant and regeneration modulator, since it exerts an effect not only on vascular tone but also on the proliferation of fibroblasts and smooth muscle cells, as well as elicits a number of other anabolic reactions (158). At the beginning of our century, works appeared in which it was demonstrated that serotonin adipinate accelerates the healing of chronic wounds in animals (72) and purulent neurotrophic ulcers of the lower extremities in diabetes in humans (109).

At the same time, in the presence of multiple causes disrupting the healing process and conditioning the development of wound complications, the solution of the problem of stimulating the healing of postoperative wounds and improving the treatment results of patients who have undergone surgical intervention using only antioxidants alone is practically impossible.

Thus, modern achievements of science in the field of molecular-cellular theory of wound healing allow a more optimistic approach to solving the problem of improving the prevention of purulent processes and stimulating wound healing in patients with diabetes mellitus after amputation of an extremity. However, existing statistical forecasts regarding the spread of diabetes mellitus and the complex nature of anatomo-functional changes in the organism of patients with diabetes mellitus complicated by gangrene of the lower extremities urgently require the conduct of detailed investigations for the further development of methods of wound healing stimulation and prevention of purulent-necrotic complications after high amputations of extremities in the categories of patients under consideration.

Goal of the Research:

To develop and implement in clinical practice a method for stimulating wound healing and preventing purulent-necrotic complications after high amputations of the lower extremities in patients with diabetes mellitus complicated by gangrene of the foot, based on the use of modern preparations possessing antioxidant action.

To achieve the set goal, the following tasks were formulated:

1. To develop and implement a method for stimulating wound healing and preventing purulent-necrotic complications after high amputations of extremities in patients with diabetes mellitus complicated by gangrene of the foot.

2. To study the dynamics of microcirculation indicators in the thigh stump after amputation of an extremity in patients with diabetes mellitus complicated by gangrene of the foot, after the course of low-intensity laser therapy and the use of modern preparations possessing antioxidant action.

3. To study the dynamics of basic homeostasis indicators in patients with diabetes mellitus complicated by gangrene of the foot, before and after performing high amputations and undergoing a course of low-intensity laser therapy in combination with the use of modern preparations possessing antioxidant action.

4. To provide a comparative evaluation of the effectiveness of the developed method of comprehensive treatment after performing high amputations of an extremity in patients with diabetes mellitus complicated by gangrene of the foot, using low-intensity laser irradiation and modern preparations possessing antioxidant action.

Scientific Novelty of the Research:

For the first time, a method for stimulating wound healing and preventing purulent-necrotic complications after performing high amputations of the lower extremities in patients with diabetes mellitus complicated by gangrene of the foot has been developed, based on the use of modern preparations possessing antioxidant action (Russian Federation Patent No. 2296515 dated April 10, 2007), making it possible to reduce postoperative mortality from 16.5% to 2.9%, decrease the number of postoperative wound healing complications by three times, and shorten the treatment duration for this category of patients by 3.9 days or by 26.4%.

For the first time, it has been established that with the use of low-intensity laser irradiation, together with the application of modern preparations possessing antioxidant action, before and after performing high amputations in patients with diabetes mellitus complicated by gangrene of the foot, normalization of basic homeostasis indicators is observed, improvement of the general condition of patients, suppression of endogenous intoxication, and restoration of the immunological reactivity of the organism.

For the first time, the state of microcirculation in the thigh stump has been studied dynamically and in a comparative plan in the early period after thigh amputation in patients with diabetes mellitus complicated by gangrene of the foot, after the course of low-intensity laser therapy and the use of modern preparations possessing antioxidant action. It has been established that the developed method of stimulating wound healing and preventing purulent-necrotic complications after high amputations of the lower extremities is effective and pathogenetically justified, ensuring in a short term improvement of the effectiveness of microcirculation in stump tissues, increase in the tissue perfusion index, optimization of vascular tone, increase in vasomotion activity, and normalization of tissue oxygen saturation.

Practical Significance:

The data obtained in the work constitute the basis for wide practical application of low-intensity laser irradiation together with modern preparations possessing antioxidant action, as adequate measures stimulating healing and contributing to the prevention of the development of purulent-necrotic complications after high amputations of an extremity in patients with diabetes mellitus complicated by gangrene of the foot. On the basis of the conducted investigations, regimens and schemes for clinical application of the studied new medicinal preparations and biologically active physical factors and their combinations have been selected, providing an adequate therapeutic effect.

Positions to be Defended:

1. The developed method of stimulating wound healing and preventing purulent-necrotic complications after performing high amputations in patients with diabetes mellitus complicated by gangrene of the foot makes it possible to reduce postoperative mortality, substantially decrease the number of complications during wound healing, and shorten the treatment duration for this category of patients.

2. The use of low-intensity laser irradiation together with mexidol, serotonin adipinate, and plant-origin polyantioxidants before and after performing high amputations of an extremity in patients with diabetes mellitus complicated by gangrene of the foot contributes to the normalization of basic homeostasis indicators, suppression of endogenous intoxication, and restoration of immunological reactivity of the organism in shorter terms than with traditional treatment.

3. The use of the developed method of stimulating wound healing and preventing purulent-necrotic complications after performing high amputations of an extremity in the category of patients under consideration contributes to a more pronounced restoration of the effectiveness of microcirculation in stump tissues, increase in the tissue perfusion index, through optimization of vascular tone, increase in vasomotion activity, and tissue oxygen saturation.

Validation of the Work:

The main results of the research were reported and discussed at the scientific-practical conference 'Actual Problems of Emergency Assistance in Practical Healthcare' in Mytishchi, 2006.

The results of the research have been implemented in the practical activity of the State Healthcare Institution GBK No. 51 of the Department of Healthcare of Moscow and the Municipal Healthcare Institution Vidnenskaya District Hospital of the Moscow Region.

Six scientific papers have been published on the topic of the dissertation, and Russian Federation Patent No. 2296515 dated April 10, 2007 has been obtained.

Volume and Structure of the Work.

The dissertation is presented on 106 pages of typed text and consists of an introduction, a literature review, 2 chapters of original research, conclusion, conclusions, and practical recommendations. The work is illustrated with 14 tables. The bibliography includes 135 domestic and 43 foreign authors.