Objectives:

• State the impact of diabetes on the risk for non-traumatic amputations.

• List the risk factors for diabetic wounds.

• List the necessary treatment components for effective wound management.

• Compare and contrast new wound treatment options.

Needs Assessment:

 Diabetes is the leading cause of non-traumatic amputations in this country. Physicians need to be aware of the risk for diabetic wounds in treating their patients with diabetes. Effective treatment protocols must be followed to successfully manage the diabetic wound. Physicians also need to be aware of the cost/benefit of new wound treatment options.

The Diabetic Wound: Are New Therapies Worth It?

Of the approximately 16 million Americans with diabetes, about 15% have or will develop foot ulcers, of which 6% require hospitalization. As the number of people with diabetes continues to increase and people live longer, we can expect the number of wounds due to diabetes to triple. No healing wounds require amputation. People with diabetes have a 15-fold increased risk of amputation in their lifetime compared to people without diabetes, a figure that has yet to change substantially. Diabetes is responsible for the greatest number of nontraumatic amputations in this country annually—about 50,000. Half of those who suffer a lower extremity amputation undergo a second amputation within a year.

Billions are spent in overall care on diabetic wounds. Amputations cost the U.S. health care system $5 billion each year. Healing each diabetic foot ulcer costs approximately $36,000. A minor amputation can cost $40,000; a major amputation can cost about $60,000.

We know much about chronic wounds in general but little about the diabetic ulcer per se. Only by understanding the biology of diabetic wounds can we improve treatment.

The following are risk factors for diabetic wounds:

• Poor glycemic control

• Vision loss

• Peripheral vascular disease

• Structural foot abnormalities

• Footwear problems

• Diabetic neuropathy

• Diabetic nephropathy

• Previous ulcer

• Prior amputation

• Poor hygiene

• Noncompliance with health care

Patient Assessment :

Many patients with non-healing wounds are not adequately assessed, leading to improper and ineffective wound care. Most patients require the expertise of a diabetologist. Proper patient assessment includes:

• Complete history

• Glycemic control

• Vascular status

• Ulcer status and duration

• Patient understanding of the problem

• Complete physical

• Nutrition

• Neurological problems

• Patient’s support network

• Prescription review

• Footwear

The vascular diagnosis is critical but often overlooked. No healing can occur unless the wound is properly perfused.

Wound Management :

It is important to involve a surgeon experienced in the treatment of diabetic wounds because complete debridement, with total excision of the wound, is needed. This provides a clean wound environment that promotes healing. Limbs can be salvaged surgically with grafts, local flaps, or free tissue transfer with microvascular techniques; these are often overlooked but more appropriate than skin replacements. Also, it is very important to solve any structural deformities before applying any other therapies. For example, tendon lengthening alone will often lead to ulcer healing as it corrects the foot deformity.

Probably the most important thing we can do is educating our patients for a lifetime with diabetes. Diabetes self-management education provides the link between medical care and the patient’s self-care. Without this link, none of the new therapies will do much good.

New Therapies :

The new therapies for diabetic wounds include growth factors, antibiotics, and skin substitutes.

Platelet-derived growth factor (PDGF) is a polypeptide, found in the a -granules of platelets and in other cells, that enters the wound at the time of injury via the platelets and then is made by other inflammatory cells. All principal cell types that migrate into the wound either synthesize and release PDGF or are responsive to it.

PDGF is chemotactic for neutrophils, macrophils, fibroblasts, and smooth muscle cells. It stimulates the proliferation of fibroblasts, smooth muscle cells, and other cells, stimulates the synthesis of collagen and other extracellular matrix proteins by fibroblasts, and stimulates angiogenesis.

The only FDA-approved PDGF is becaplermin (Regranex gel). It is indicated for the treatment of lower-extremity diabetic ulcers that are 1) not infected and 2) have a good vascular supply. Unfortunately, it is often used for wounds where these conditions are not met. Becaplermin exhibits biological activity similar to endogenous PDGF: It promotes chemotactic recruitment and proliferation of cells involved in wound repair and enhances the formation of granulation tissue.

A retrospective analysis of patients treated with becaplermin supported the healing properties of this drug but also illustrated the importance of complete debridement. Becaplermin treatment accelerated closure by up to 80% in wounds that had been excised surgically. The study site with the highest debridement rate had the highest healing rate; conversely, the study site with the lowest debridement rate had the lowest healing. The Achilles’ heel of becaplermin is wound proteases. Topically applied growth factors can be promptly degraded by excessive proteolytic enzymes found in many chronic wounds. Proper debridement transforms the wound environment into one with a favorable protease/antiprotease profile.

Antibiotics are helpful in wound healing. All chronic wounds are contaminated, but not all are infected. Infection is defined as >105 bacteria per gram of tissue, although quantitative bacteriology is not easy to obtain for every ulcer. Bacterial counts can be lowered with debridement by knife and with dressings and topical antibiotics, all of which promote healing. The efficacy of topical versus systemic antibiotics is up for debate.

Just one skin substitute is in line for FDA approval for use in diabetes: a collagen matrix with fibroblasts and allograft epithelial on top (Apligraft), and other types exist (collagen matrix with silicone on top for later autograft replacement, and biomaterial with allograft epithelial on top). There is an increased rate of wound closure in diabetic ulcers treated with Apligraft. However, wound collagenase and elastase destroys this material, and it is possible that a small allograft would work just as well. Although the data have a significant "p" value, Apligraft is an expensive treatment option, and its cost and benefit should be weighed against other treatment options.

Summary :

With proper medical skills and patient education, new wound management technologies may not be needed. Treating doctors must understand the diabetic wound. Patients must be educated to become partners in the treatment. Surgeons must be involved in wound management because complete wound debridement is essential for healing. The future holds advances in protease inhibitors, both in the form of drugs and dressings to remove proteases, and new methods for bacterial control.

Reference :

1. Steed DL, et al.: Effect of extensive debridement and treatment on the healing of diabetic foot ulcers. Diabetes Ulcer Study Group. J Am Coll Surg 183:61164, 1996.