The Diabetic Foot: Treatment

The Diabetic Foot: Treatment

Dr. S.M.Sadikot (Mumbai)
Consultant in Endocrinology,
Diabetes and Metabolic Disorders,
Jaslok Hospital and Research Centre, Mumbai.

Foot problems in a person with diabetes are one of the most common complications seen in India. Although intensive efforts need to be made to avoid these foot complications, it is more easily said than done, especially in our country where walking barefoot is much more common than in the West. The reality is such that often the presenting complaint of a person with diabetes is a major foot infection, often with non healing ulceration. The morbidity, and sometimes, the mortality, associated with these complications are immemnse not only from the purely medical viewpoint, but also from the socioeconomic and psychological aspects. In fact, it has been shown that after accidents, diabetes associated foot problems are the secong most common cause of lower limb amputations in India. Patients with diabetes mellitus may present to the diabetes mellitus may present to the primary care practitioner with dangerous lower-extremity sequelae that are extremely challenging to treat. The high incidence of amputation in this patient population is, line large part, the result of uncontrolled infection and ulceration of the foot.

All diabetic patients are prone to developing infections of the foot . Once established, these infections are more severe and more treatment - refractory than in nondiabetics. If left unchecked these infection may progress to cellulitis.

Foot infection in diabetics develops because of coexisting angiopathy, immunopathy, and neuropathy. Angiopathy begins at the microvascular level, with thickening of the basement membrane and reduced blood flow. This often leads to platelet aggregation and a further decrease in perfusion and oxygenation of foot tissues, together with reduced chemotaxis of neutrophils, macrophages, and other protentially protective cells. Immunopathy is the result of prolonged periods of hyperglycemia, which reduce the ability of these cells to phagocytize bacteria.

Neuropathy impairs the structural integrity of the foot while decreasing the perception of injury. Bacteria gain access via open wounds, including fissures and punctures in the insensate foot. However , many diabetic patients who present with a cellulitic foot do not have an obvious open wound, cellulitis may be the result of hematogenous bacterial spread from a urinary or respiratory tract infection to which diabetics are also susceptible. these patients present with the cardinal signs of infection - erythema, edema, and calor.

The causative pathogens are varied and can range from aerobic organisms such as Staphylococcus aureus, group B Streptococcus, Enterococcus, Coagulase-negative Staphylococcus, Proteus mirabilis, Proteus vulgaris, Enterbacter, Citrabacter, and Serratia. Pseudomonas has also been isolated from diabetic foot infections secondary to long - standing open ulcerations. In addition , anaerobic organisms such as Bactericides, Peptococcus, and peptostreptococcus are often identified.

Infection with several organisms is common. One should therefore perform both aerobic and anaerobic cultures, from sample material taken from the deeper parts of the wound.

Empiric Antibiotic Therapy

Because of the frequency of polymicrobial involvement empiric treatment should cover Gram- negative aerobic as well as an aerobic organisms. The antibiotic chosen should be bactericiadal as opposed to beacteriostatic. In general, bacteriostatic antibiotics require an intact immune system to function properly.

Mild or Moderate Infections

Treat mild infections with broad - spectrum oral antibiotics such as amoxicillin/clavulanic acid, clindamycin, cefuroxime axetil, or cephalexin. This can be done on an outpatient basis. It is not necessary to culture superficial diabetic wounds. Moderate infection require treatment with intravenous antibiotics on an impatient basis. Broad - spectrum antibiotics such as imipicillin/sulbactam,piperacillin/tazobactam,ticarcillin/clavulanic acid, clindamycin or a fluoropuinolone should provide adequate coverage. Although clindamycin is a bacteriostatic antibiotic, its antibacterial activity has been shown to be bacteriocidal at higher dose concentrations. The newer third - and fourth - generation fluoroquinolones, some not yet widely available in India,-levefloxacin, grepafloxacin, sparfloxacin, and trovafloxacin - are particularly effective against polymicrobial infections.

Abscesses

After 2 to 3 days of antibiotic therapy, cellulitis often localizes to one area of the foot resulting in the formation of an abscess. Proper management of the abscess entails incision and drainage. In addition,obtain deep specimens intraoperatively for culture and sensitivity testing. These abscesses are often polymicrobial and filled with many contaminants. After removing all necrotics debris , irrigate the wound with normal sterile saline using a power irrigation pulse lavage system, which will enable you to dilute the concentration of invading bacteria. A bacterial count of at least 105 per mm3 of soft tissue will establish an infection; therefore , dilution of bacteria in infected tissue is an essential adjunct to infection control.

Severe Infections

Severe infections (which are all life threatening )are characterized by massive cellulitis with ascending lymphangitis. The patient is likely to have sepsis, fever, and a significantly elevated white blood cell count. Narcotizing facetious with liquefaction necrosis and gas formation in the soft tissues may also be present. The antibiotic of choice is imipenem/cilastatin. However, ampicillin/sulbactam has proved effective in treating limb-threatening infections Synergistic antibiotic therapy including third - or - fourth - generation cephalosporin, ticarcillin/clavulanic acid, piperacillin/tazobactam, imipenem, or meropenem, each together with an aminoplycoside, are also effective attaints limb threatening infections.

In addition, one should seek surgical consultation for wide incision and drainage, debridement, and possibly, for ablative open guillotine amputation as a life-saving measure.

In investigating the different treatment options for foot infections in patients with diabetes without systemic infection, one study has found that the least expensive approach was prolonged treatment with oral antibiotics following initial hospitalization for surgical debridement; the most expensive approach was immediate amputation. A second study has found that debridement and , if indication , revascularization, resulted in long - term salvage of threatened feet, even in high - risk patients even with gangrene. A third study has found that early amputation in patients with foot infections who were not candidates for arteroa; reconstruction permitted early rehabilitation, decreased long - term morbidity, and reduced overall cost.

Ulceration's

Diabetic foot ulceration's will heal under four conditions- adequate peripheral perfusion, control of infection, off-loading of pressure-sensitive or ulcerated areas, and control of diabetes, including concurrent systemic diseases. off - loading the wound can be accomplished externally or internally. Shoe modification padding, debridement of surrounding hyperkeratotic tissue , and total contact casting are forms of external off-loading. Bunionectomy, hammer toe correction, metatarsal head resection, and other exostosectomies are means of off-loading internally . If the diabetic patient has adequate peripheral perfusion and is stable, surgical removal of pressure areas can accelerate ulcer healing.

Wagner Ulcer Grade Classification

Grade Wound Characteristics
0 Pre-ulcerative lesions, healed ulcers, presence of bony deformity
1 Superficial ulcer without subcutaneous tissue involvement
2 Penetration through the subcutaneous tissue; may expose bone, tendon, ligament of joint capsule
3 Osteitis, abscess, or osteomyelitis
4 Gangrene of digit
5 Gangrene of foot requiring disarticulation

Various classification schemes have been devised to aid in the diagnosis treatment, and prognosis of ulceration's. The most valuable scheme to be the one developed in 1981 by F. William Wagner. This scheme is based on the depth of the lesion and involves six stages ranging from no ulcer to gangrene of the entire foot. Wagner's scheme serves three very important purposes: to help standardize treatment plans; to help standardize treatment plans; to increase the level of communication between practitioners caring for the same patient; and to identify positive and negative changes in the progress of treatment.

The treatment of Wagner grade ) lesions - prominent osseous structures (e.g., bunions, hammer toes) and calluses - mainly involves prevention. For example, if a callus has formed because of abnormal stress on an area of the foot, remove the source of stress by padding the shoes or by recommending better- fitting shoes . In some cases , it may be beneficial to debride the callus as well. DeBridement serves to offload the area and permit identification of any ulceration under the callus that might have gone unnoticed. Padding the shoes is also recommended if a significant bony prominence is present without a callus. The main goal is to prevent the progression of a grade ) lesion to the status of a superficial ulcer.

These are superficial ulcers, which often have a base of necrotic tissue. The chronic neuropathic ulcer matrix is hypoxic, acidic and hypoglycemic. Attempted healing via smooth muscle myofibril contraction is often inadequate to close the wound. Necrotic tissue that is present both inhibits epithelialization and provides a culture medium for bacterial growth ; thus , it is impotent to debride the wound. The purpose of debridement is to convert the chronic would matrix into an acute wound. Matrix by removing necrotic debris, bacteria and surrounding hyperderatitic tissue. Aggressive sharp debridement provides a good granular, bleeding bed at the base of the wound which permits an influx of platelets and platelet - derived growth factors needed for healing . Debridement should be performed on a weekly basis until healing is complete.

Wet - to - dry dressings (soaked in saline but allowed to dry before removal) applied every 6 to 8 hours provide a moist environment for the wound to heal . Once the dressing dries , removal serves the function of debridement by eliminating any necrotic tissue adhering to the bandage. One now implements wet-to-moist dressing changes because we believe that removal of the dry dressings tends to damage the wound , impairing reepithelialization by inhibiting retye peg formation the subsequent epidermis is fragile and easily damaged which results in a high recurrence of locer formation the patient should perform wet-to-moist dressing changes once or twice daily. (Wet-to-dry dressing changes should be done once a day.)

In addition to aggressive debridement and wet-to-moist dressing changes, one can apply a new topical gel to diabetic wounds. Becaplermin 0.1% is a recombinant endogenous human platelet-derived protein growth factor(PDGF-BB) gel that has a chemoattractant effect on local and surrounding undifferentiated mesenchymal cells recruiting fibroblasts and inflammatory and smooth muscle cells. It is indicated for the treatment of diabetic neuropathy rekated lower-extremity ulcers that extend into the subcutaneous tissue or beyond and have an adequate blood supply. The PDGF binds with the alpha receptor sites found in the acute wound matrix. Therefore, initial wide debridement of a nonhealing diabetic foot ulcer is recommended to convert the chronic wound matrix into an acute wound matrix exposing a significant number of these alpha receptor sites. With the application of becaplermin routine debridement of the ulcer on subsequent office visits is discouraged, as that tends to disrupt these receptor sites, thereby decreasing the effectiveness of PDGF. Debridement of the hyperkeratotic periphery of the ulcer is recommended to off-load undue pressure on the surrounding skin. If significant necrotic or fibrous tissue redevelops during the course of PDGF treatment, intermittent wide debridement by a qualified have shown that the combination of good wound care - aggressive debridement , infection control and pressure relief - and the application of becaplermin gel increase the rate of wound healing.

These are deepulcers that extend toligaments , tendons , muscle, and / or bone . Treatment is essentially the same as that for grade 1 ulcer . The main emphasis is on prevention of infection, which may necessitate amputation . Some patients with grade2 ulceration's require aggressive debridement in an operating room setting.

These deep ulcers are marked by abscess formation cellutlitis , osteomyelitis, and /or tendinitis. They require a more aggressive form of treatment. A new class of antiniotis , which works by attacking the bacterial cell's membrane has been developed . The first antibiotic in this class , the topical gel pexiganan acetate, is currently being studied for the treatment of diabetic foot ulcers. The result look promising. If clinical signs and plain x-rays suggest ostemoyelitis, order a 3 phase technetium bone scan. Technetium-labelled white blood cell bone scan are specific for osteomyelitis and can confirm the diagnosis when other osseous abnormalities cannot be ruled out. Once the diagnosis of osteomyelitis is confirmed, the treatment usually entails surgical excision of all infected bone and tissue . It is often necessary to amputate digits and / or remove portions of the metatarsals. In cases with minimal bone involvement , a 6 week course of intravenous antibiotics is recommended.

These deep lesions involve gangrene of any part of the forefoot. When one deals with gangrenous changes, the main goal is to prevent "wet "gangrene from developing . A combination of gangrenous changes, deep infection and gas in the tissues almost always spreads rapidly up the leg (narcotizing fascists). Amputation of all gangrenous and infected tissue is the treatment of choice.

These deep lesions involve gangrenous changes in the rearfoot or the entire foot. They often require below the knee amputation.

Another classification which has been seen to be of significant value in the valuation and management of the diabetic foot is The University of Texas Diabetic Foot Classification.

Category 0 Category 1 Category 2a Category 3a
No Pathology Neuropathy, No Deformity Neuropathy with Deformity History of Pathology
Patient diagnosed with diabetes mellitus Protective sensation absent by Semmes Weinstein test Protective sensation absent Protective sensation absent
Protective sensation intact by Semmes Weinstein test ABI > 0.8 and toe systolic pressure > 45 mm Hg ABI > 0.8 and toe systolic pressure > 45 mm Hg ABI > 0.8 and toe systolic pressure > 45 mm Hg
Ankle-brachial index (ABI) > 0.08 and toe brachial index > 0.45 mm Hg No history of ulceration History of neuropathic ulceration No history of neuropathic ulceration
Foot deformity may be present No history of Charcot's joint No history of Charcot's joint History of Charcot's joint
No history of ulceration No foot deformity Foot deformity present Foot deformity present

Possible Treatment

Shoe accommodations

Patient education

Follow up 6 to 12 months

Possible Treatment

Same as category 0 plus: Possible shoe gear accommodation

Quarterly visits to assess shoe gear and monitor for signs of irritation

Follow up 3 to 4 months

Possible Treatment

Same as category 1 plus:

Pedorthist/orthotist consultation for possible custom-molded/ extra-depth shoe accommodation

Possible prophylactic surgery to alleviate foot deformity

Follow up 2 to 3 months

Possible Treatment

Same as category 2 plus:

Pedorthist/orthotist consultation for possible custom-molded/ extra-depth shoe accommodation

Possible prophylactic surgery to alleviate foot deformity

More frequent visits may be indicated for monitoring

Follow up 1 to 2 months

Category 4A Category 4B Category 5 Category 6
Neuropathic Wound Acute Charcot's Foot The Infected Diabetic Foot The Ischemic Limb
Protective sensation absent Protective sensation absent Protective sensation may be present Protective sensation may not be present
ABI > 0.8 and toe systolic pressure > 45 mm Hg Hg ABI > 0.8 and toe systolic pressure > 45 mm Hg Infected wound ABI < 0.8 or toe systolic pressure < 45 mm Hg or pedal transcutaneous oxygen present tension < 40 mm Hgtension < 40 mm Hg
Foot deformity normally present Non-infected neuropathic ulcer may be present Charcot's joint may be present Ulceration may be present
No Charcot's joint present Charcot's joint present

Possible Treatment

Debridement of infected, necrotic tissue and/or bone as indicated

Possible hospitalization, institute antibiotic regimen

Medical management

Possible Treatment

Vascular consult, possible revascularization

If infection present, treat as in Category 5. Vascular consultation with control of sepsis

Possible Treatment

Same as category 3 plus:

Pressure reduction program instituted

Wound care program instituted

Possible Treatment

Same as category 3 plus:

Pressure reduction program instituted

Thermometric and radiographic monitoring

If ulcer present, same treatment as category 4A

The moist wound healing concept is widely accepted in treating DFUs. Some of the benefits of this approach include prevention of tissue dehydration and cell death, acceleration of angiogenesis, and facilitating the interaction of growth factors with the target cells. The standard of care recommended by the American Diabetes Association is saline-moistened gauze. The "wet-to-dry" concept is no longer acceptable because if the gauze becomes dry before the next dressing change, it may cause damage to the wound bed and disrupt the healing process. Hydrocolloid dressings and hydrogels can maintain the moist wound environment while providing some autolytic debridement. Enzymatic debridement agents can be helpful for necrotic tissues. The alginates and absorptive dressings absorb drainage well and maintain moist wound environments. Other dressings are impregnated with collagen, zinc, or other factors that stimulate wound healing. Some dressings have a coated antimicrobial barrier. Composite dressings have more than one characteristic promoting wound healing. Contact-layer dressings prevent damage to the wound bed. Foam dressings may provide some padding in addition to absorbency. There have been no large, controlled studies to show the efficacy of hyperbaric oxygen therapy and electrical stimulation on DFUs.

Becaplermin gel is a platelet-derived growth factor (PDGF) of recombinant human origin. PDGF stimulates and recruits macrophages, neutrophils, and fibroblasts; stimulates angiogenesis; and stimulates granulation tissue formation, wound contraction, and wound remodeling. Becaplermin gel should be used in wounds that have adequate blood supply and a clean wound bed (one without infection or necrosis). When used in conjunction with appropriate wound care, becaplermin gel has been shown to increase the incidence of complete wound closure (50% versus 35% for placebo) and decrease the time to complete wound closure (86 versus 127 days).

The amount of becaplermin gel applied varies by wound size (see Table 1). The amount should be measured out onto a clean surface and the gel applied using an application aid (Q-tip, etc.) to a thickness of 1/16 inch. The gel should be covered with a saline-moistened gauze pad and left in place for 12 hours. After 12 hours, remove the gauze, rinse the ulcer with saline, and apply a new moistened dressing (without becaplermin gel) for the remaining 12 hours. Repeat this application process once daily.

In inches
  • Measure the greatest length and width of ulcer in inches.
  • Calculate the length of gel (in inches) required from a 15 gram tube by multiplying the length x width x 0.6.
  • Each square inch of ulcer surface requires approximately 2/3-in. length of gel.
In centimeters
  • Measure the greatest length and width of the ulcer in centimeters.
  • Calculate length of gel that should be squeezed from a 15 gram tube by multiplying the length x width divided by 4.
  • Each square centimeter of ulcer surface requires approximately 0.25-centimeter length of gel.

Living skin equivalent (LSE) products are the newest technological advances for diabetic foot ulcers. One LSE product consists of dermal fibroblasts cultured in vitro onto a bioabsorbable mesh to produce a metabolically active tissue that has histological characteristics similar to the dermal papillary of newborn skin. The first large prospective study showed some promising results; another study is underway.

Another available LSE product resembles living human skin in that it consists of two primary layers: an epidermis and a dermis. The well-differentiated epidermal layer includes a protective stratum corneum formed from human living keratinocytes. The dermal layer is composed of living human fibroblasts dispersed in a bovine collagen matrix. The keratinocytes and fibroblasts are cultivated from human infant foreskin. A prospective, randomized, controlled, clinical trial was performed to evaluate the safety and efficacy of this LSE in the treatment of diabetic foot ulcers. The result from a single center revealed that this LSE significantly healed more ulcers (75% vs. 41% wound healing in 12 weeks) and in less time (38.5 days vs. 91 days) compared to standard treatment alone. The multi-center result showed similar efficacy; 56 percent of ulcers treated with the LSE healed within 12 weeks compared to 38 percent for standard treatment alone, with complete healing achieved on the average of 65 days compared to 90 days. The LSE was not associated with any significant side effects when compared to standard care alone. Recently, the FDA has approved this LSE for use in treatment of diabetic foot ulcers.

The skin equivalent used in the study is a bilayered, living human skin analog that consists of both a dermal and epidermal layer. The dermis is made from human cultured fibroblasts (from donated neonatal foreskin) and purified bovine collagen. The epidermis consists of keratinocytes that are also derived from the neonatal foreskin. Compared to normal skin, the skin equivalent is devoid of major immunogenic components, resulting in a lack of immunological response and rejection reaction when applied in human wounds. Application of the skin equivalent may stimulate healing through the action of cytokines and other matrix components that stimulate epithelialization from the edge of the wound and promote the formation of new skin at the applied area, resulting in frank graft take which leads to a graft integration similar to the one observed autologous skin grafting.

Bioengineered tissue has been shown in one report to heal statistically significantly more wounds than control treatment (50.8% versus 31.7%) after 12 weeks of therapy.[24] Currently, there are two bioengineered tissue products, Apligraf and Dermagraft. Apligraf is approved by the Food and Drug Administration for treatment of skin ulcers caused by venous insufficiency, and recently received FDA approval for treatment of diabetic foot ulcers when other traditional treatments have failed. Dermagraft is not currently marketed in the United States.

Modern technology has led to an explosion of new wound dressings, topical products, and living skin equivalents in the last few years. All new techniques and products should be rigorously tested for safety and efficacy before patient application or use. The studies and clinical trials involving these devices and products should be prospective, randomized, and well controlled. The results of studies should be compared to accepted gold standards or to clearly defined measurements. The conclusions drawn from the studies should be supported by the results.

Inspite of all these advances, extensive debridement of the ulcer area, intensive treatment of the infection, abolition or significant reduction of the trauma related to weight-bearing at the ulcer area, and adequate restoration of the blood flow, when required, are absolute prerequisites for successful wound healing and cannot be replaced by any new therapeutic intervention, including the application of living human skin equivalents.

One Protocol which we have found quite useful is given below as a flow chart

Management of Foot Ulcers in patients with Diabetes
1. Patients with diabetes present with complaints consistent with a foot ulcer
2.Determine the extent of tissue injury and involvement (see explanatory text and appendix 1.)
3.For tissue which is minimally injured (e.g, Wagne 0 or UT categories 0-2)institute prevention therapies for all ulcers, go to Box 4. Editors note: Bold fonts indicates algorithm steps which has to be completed at the same visit
4.Is the Ulcer infected 5. Is the ulcerated area adequately perfused Consult a vascular surgeon or a vascularist
Yes
Yes
6.Institue systemic antibiotics and wound care(see text). 7. Is the ulcer on a weight- bearing surface No 8.Treat the ulcer with conventional wound management and reasses in 2-4 weeks. Go to Box 10.
Yes
Yes
Go to Box 5 9. Institute off-loading and or bed rest Go to box 8 10. Is the treatment successful No 11.If progressive but incomplete wound closure or treatment unsuccessful consider use of becaplenmin gel therapy bioengeneered tissue or surgical wound closure. Continue appropriate wound management practices as described in text.
Yes
Yes
12. Institute preventive therapies as described in Box 3 13. Institute Therapy for 3-8 weeks assess ulcer healing
14. Has the wounds worsened or shown no change Yes 15. Returns to box 4 and reassess the wound for infection, vascular status, and weight bearing status and the patient adherence to the prescribed regimen. Consider referral to a wound specialist
16. Continue therapy and freasses healing with frequent follow-up visits (every 1-2 weeks)
17. Has the wound responded No 18. Return to Box 4. and reassess the wound for infection. Vascular status and weight bearing status and the patients adherence to the prescribed regime. If the wound has been treated for so long without progress or if the wound has worsened refer the patient to the wound specialist
Yes
19. If not completely closed continue therapy and appropriate wound management. Once closed institute preventing therapies indicated in Box.3.

Foot problems in a person with diabetes can have disastrous consequences. Though recent advances in the management of these problems have increased our abilities to save the lower limb, the best management still remains prevention. This can only follow with intense patient education about foot care and a proactive role in treating the factors which lead to these foot problems.

Even if foot problems do occur, they must be recognised early and prompt and rigorous treatment at this stage can go a long way to prevent the more serious sequelae.