Wound care
Wound-bed preparation reduces the wound margins to well-vascularized granulation tissue without signs of local infection and promotes the healing process.1,2 The Wound Healing Society defines a chronic wound as one that fails to proceed through an orderly and timely repair process.2,6 There are four phases to the wound healing process: coagulation, inflammation, proliferation, and tissue remodeling.
Debridement of necrotic tissue is a crucial first step in treating diabetic foot ulcers. Patients should be referred for surgical debridement early.8 The procedure should be comprehensive, removing all nonviable tissue and extending the wound margins 2 to 3 mm into healthy, nonhyperkeratotic skin.2,9,17 There are four types of debridement: surgical, enzymatic, autolytic, and mechanical. Surgical and mechanical debridements use some type of trauma to remove tissue, while autolytic and enzymatic debridements use a more natural method. Debridement removes local bacteria, stimulates healing, documents absence of hyperkeratosis, and decreases local infection.
The dressing used on a debrided ulcer should provide a moist environment to minimize trauma and reduce risk of 
infection.1,2,6 Wet-to-dry dressing with normal saline is considered the standard of care. The tissue must be kept moist to avoid devitalization and deepening of the ulcer.9 One alternative to wet-to-dry dressings is the use of platelet-derived growth factor (PDGF), an endogenous protein that exerts a tremendous influence on tissue granulation and thereby improves wound healing.2,4,18 PDGF has been shown to stimulate chemotaxis and mitogenesis of the neutrophils, fibroblasts, and monocytes by which wound healing can occur.2,4,9,13,18 A third option is to use dermal/skin substitutes. They function as biological dressings, delivery systems for growth factors, and extracellular matrix components.1,2,9,13
Intermittent hyperbaric oxygen (HBO) therapy may help salvage marginally perfused tissue. With HBO therapy, the patient breathes 100% oxygen while inside a pressurized treatment chamber.19,20 It is believed that this increases the oxygen tension in the wound, thereby increasing granulation tissue formation and accelerating wound contraction. Some reports show that HBO therapy reduced the number of major amputations in patients with diabetes.21 HBO therapy relies on the presence of an adequate blood supply to the wound, and conflicting data on its effectiveness make this treatment controversial. Therefore, it should be used in conjunction with standard therapy and only after other methods have failed. Patients who have dysbarism and those who have claustrophobia should not receive this treatment.4,6,19-21
Infection treatment
Because of the high incidence of infection associated with diabetic foot ulcers, a systematic approach for a complete assessment is required. Foot ulcers are entry portals for systemic infection, and when left untreated, they are a threat to life and limb. Determining the severity of infection is important according to the Infectious Diseases Society of America.22 In a mild infection, there is less than 2 cm of erythema; in a moderate one, there is more than 2 cm of erythema; and in a severe one, both infection and systemic toxicity are present.22 Infection is presumed if erythema, warmth, tenderness, swelling, or pus oozing from the wound is noted.5 Initial indications are an increase in temperature compared to the other foot, a malodorous discharge, erythema, swelling, and tenderness.4,11
Patients with cellulitis often do not feel pain because of the sensory neuropathy. The diagnosis is usually made 
by clinical appearance.22 Typically, osteomyelitis occurs gradually over a few days to a week and produces fever and rigors.23 Constitutional symptoms such as nausea, vomiting, malaise, and fatigue are other important clinical clues to osteomyelitis. Frequently, however, the only indication of infection may be unexplained hyperglycemia. Infections often begin around the toenail bed, at cracks in the skin, or in ischemic ulcers.2,22
If an ulcer is infected, the patient should be evaluated for extent of infection, glycemic control, and loss of sensation.22 The ulcer should be probed to determine bone involvement, sinus tract formation, and extension into the tendon sheaths.2 Deep cultures should be taken because superficial cultures grow only skin flora.1,6,8,9 Diabetic foot infections are commonly polymicrobial, containing both aerobic and anaerobic bacteria.1 Necrosis or a fetid odor indicates an anaerobic infection.17
Leukocytosis is usually found in acute osteomyelitis but not in chronic osteomyelitis.23 If the bone is exposed, the patient is assumed to have osteomyelitis.2 Patients with soft tissue infections lasting longer than 2 weeks, especially over a bony prominence, are at high risk for this condition. The definitive method of diagnosing osteomyelitis is by bone biopsy, but this is not always practical or possible.22 The ESR is a specific but insensitive diagnostic tool; it is frequently elevated above 100 mm/h in osteomyelitis but can be normal. Furthermore, the ESR often is inaccurate in patients with end-stage renal disease or nephrotic syndrome. However, an ESR higher than 70 mm/h with a 3-mm ulcer is specific for osteomyelitis. A high ESR can be particularly helpful in detecting a relapse.23
Imag
ing studies can be helpful in assessing diabetic foot infections. However, radiologic changes occur late in the course of osteomyelitis, so a negative radiograph does not rule out this diagnosis.13 Osteomyelitis is not visible on plain radiographs until 10 to 14 days after the onset of bone involvement.2 Radionuclide bone scans
may show abnormalities earlier than radiographs, but they are less specific when bone turnover is high.1,2 MRI is the procedure of choice for diagnosing osteomyelitis in patients with diabetes. A drawback is that it cannot distinguish whether abnormal bone marrow edema is due to neuropathic changes or osteomyelitis. The changes seen on MRI are not pathognomonic of osteomyelitis but can be used as a basis for initiating treatment or proceeding to bone biopsy. Indium-labeled leukocyte scanning uses radioactive indium as the tracer; it accumulates in the bone marrow at the site of infection or inflammation. It is more reliable than plain imaging but has a lower specificity and sensitivity than MRI.13,22,23
Diabetic foot infections are divided into non-limbthreatening and limb-threatening. In non-limb-threatening infections, cellulitis is less than 2 cm deep and does not extend to the bone or joint, and there is no evidence of systemic toxicity. In limb-threatening infections, cellulitis is more than 2 cm deep and extends to the bone or joint, and systemic infection is present.2,6 Hospitalization for limb-threatening infections is mandatory. 2,22 Mild soft tissue infections are treated with oral antibiotics for 1 to 2 weeks, but deep infections require broad-spectrum IV therapy and deep surgical debridement.1,6,9,15,22
Empiric therapy should be started initially and cultures obtained. Once the pathogen causing the infection is identified, therapy can be switched to an agent that is specific for that organism. IV therapy should usually continue for 6 weeks, but shorter courses can be used if the affected bone has been resected. Moderate and severe infections, which often are polymicrobial, require 2 to 4 weeks of IV therapy, switching to oral therapy after a good response.2,6,22
Pressure relief
Off-loading, also called pressure relief, is the third principle of treatment 24 (see Table 6). Bed rest, an ideal pressure relief measure, often is impractical.16 Offloading is limited by the patient's physical characteristics and ability to comply with treatment and by the location and severity of the ulcer.24,25 The heel is the most difficult plantar area to off-load; a wheelchair or crutches may be required.25 Despite these drawbacks, off-loading remains the gold standard for ulcer treatment and for preventing recurrence.25
Total contact casting (TCC) is the most effective method of off-loading. A total contact cast is a special cast designed to redistribute the patient's weight off the ulcer site, allowing ambulation while the ulcer is healing. The major drawbacks are that TCC limits access to the ulcer for dressing changes and wound inspection and that it requires a technician specifically trained in its application.1,2,4,6,8,9 The patellar tendon-bearing brace is expensive and challenging to make but allows for considerable mobility while off-loading the entire foot.25 Surgical shoes can be used in place of TCC, but they are not as effective and must be worn even when the patient takes one or two steps.17 In patients with foot deformities, an orthopedic evaluation should be considered. 13 Surgical treatment corrects the foot deformity and improves foot mechanics.25
Conclusion
Many amputations resulting from diabetic foot ulcers are preventable with a thorough evaluation and aggressive treatment. The most important primary preventive measures are properly fitting socks and shoes and good control of blood glucose and lipid levels and of BP. A comprehensive, multidisciplinary evaluation, including determination of etiology, is essential in treating the diabetic foot ulcer.
The primary objective is to heal the ulcer and prevent amputation. Patients with an infected foot ulcer benefit from early, aggressive treatment that encompasses debridement, good wound care, and pressure relief. An infected diabetic foot ulcer requires close supervision whether it is limb threatening or not. A radiograph of the foot is acceptable initially, but a technetium scan or MRI may be warranted to confirm the clinical assessment. Antibiotic coverage should be broad spectrum and tailored to the patient. JAAPA
REFERENCES
1. Brem H, Sheehan P, Boulton AJ. Protocol for treatment of diabetic foot ulcers. Am J Surg. 2004;187(5A):1S-10S.
2. Frykberg RG, Armstrong DG, Giurini J, et al. Diabetic foot disorders: a clinical practice guideline. American College of Foot and Ankle Surgeons. J Foot Ankle Surg. 2000;39(5 suppl):S1-S60.
3. Uccioli L. Clinical results related to the use of the TissueTech Autograft System in the treatment of diabetic foot ulceration. Wounds. 2003;15(9):279-288.
4. Eldor R, Raz I, Ben Yehuda A, Boulton AJ. New and experimental approaches to treatment of diabetic foot ulcers: a comprehensive review of emerging treatment strategies. Diabet Med. 2004;21(11):1161-1173.
5. McCulloch DK. Evaluation of the diabetic foot. UpToDate. Available at: http://www.uptodate.com. Accessed November 27, 2006.
6. Daugherty KK, Adams AG, Piascik P. Treatment of diabetic foot ulcers in elderly patients. Clin Geriatr. 2000;8(7):75-86.
7. Bennett SP, Griffiths GD, Schor AM, et al. Growth factors in the treatment of diabetic foot ulcers. Br J Surg. 2003;90(2):133-146.
8. Epstein DA, Corson JD. Surgical perspective in treatment of diabetic foot ulcers. Wounds. 2001;13(2):59-65.
9. Frykberg RG. Diabetic foot ulcers: pathogenesis and management. Am Fam Physician. 2002;66(9):1655-1662.
10. Kaufman MW, Bowsher JE. Preventing diabetic foot ulcers. Medsurg Nurs. 1994; 3(3):204-210.
11. Inlow S, Orsted H, Sibbald RG. Best practices for the prevention, diagnosis, and treatment of diabetic foot ulcers. Ostomy Wound Manage. 2000;46(11):55-68.
12. Snyder RJ. Treatment of diabetic foot ulcers: an interdisciplinary approach. Podiatry Manage. 1999;18(5):61-70.
13. McCulloch DK, Hordon LD. Management of diabetic foot lesions. UpToDate. Available at: http://www.uptodate.com. Accessed November 27, 2006.
14. Kalker AJ, Kolodny HD, Cavuoto JW. The evaluation and treatment of diabetic foot ulcers. J Am Podiatry Assoc. 1982;72(10):491-496.
15. Sage R, Doyle D. Surgical treatment of diabetic foot ulcers: a review of forty-eight cases. J Foot Surg. 1984;23(2):102-111.
16. Spencer S. Pressure relieving interventions for preventing and treating diabetic foot ulcers. Cochrane Database System Rev. 2000;(3):CD002302.
17. Miller OF 3rd. Essentials of pressure ulcer treatment. The diabetic experience. J Dermatol Surg Oncol. 1993;19(8):759-753.
18. Steed DL. Platelet-derived growth factors in the treatment of diabetic foot ulcers. Wounds. 2000;12(6):95B-98B.
19. Kalani M, Jorneskog G, Naderi N, et al. Hyperbaric oxygen therapy in the treatment of diabetic foot ulcers: long-term follow-up. J Diabetes Complications. 2002;16(2): 153-158.
20. Senior C. Treatment of diabetic foot ulcers with hyperbaric oxygen. J Wound Care. 2000;9(4):193-197.
21. Kessler L, Bilbault P, Ortega F, et al. Hyperbaric oxygenation accelerates the healing rate of nonischemic chronic diabetic foot ulcers: a prospective randomized study. Diabetes Care. 2003;26(8):2378-2382.
22. Weintrob AC, Sexton DJ. Management of diabetic foot infections. UpToDate. Available at: http://www.uptodate.com. Accessed November 27, 2006.
23. Ghiorzi T, Mackowiak P. Diagnosis of osteomyelitis in adults. UpToDate. Available at: http://www.uptodate.com. Accessed November 27, 2006.
24. Knowles EA, Armstrong DG, Hayat SA, et al. Off-loading diabetic foot wounds using the scotchcast boot: a retrospective study. Ostomy Wound Manage. 2002;48(9):50-53.
25. Inlow S, Kalla TP, Rahman J. Downloading plantar foot pressures in the diabetic patient. Ostomy Wound Manage. 1999;45(10):28-38.