Diabetic foot ulcers and infections: Current concepts

Advances in Skin & Wound Care, Jan/Feb 2002 by Calhoun, Jason H, Overgaard, Kristi A, Stevens, C Melinda, Dowling, James P E, Mader, Jon T

Infection can cause pedal ischemia and decrease oxygen levels. The decrease in the partial pressure of oxygen at the periphery of the wound will impede the growth of new tissue into the wound space. Diabetic wound infections are polymicrobial with a high incidence of anaerobes. Elevated tissue oxygen levels improve leukocyte killing of bacteria6,61 and are toxic to anaerobic organisms.

Although HBO therapy causes local vasoconstriction, the overall increase in blood oxygen levels results in a net gain that increases the oxygen concentration at the wound level. If the patient has adequate arterial circulation, HBO therapy may significantly assist the wound healing process. A common method for evaluating patients for HBO therapy is through the use of transcutaneous oximetery. Normal TcP02 values in the lower extremities are at least 40 mm Hg. If the value is lower in a diabetic patient with a nonhealing foot ulcer, he or she may be a good candidate for HBO therapy.

Several anecdotal and retrospective studies support HBO therapy as effective adjunctive therapy in the medical and surgical management of diabetic wounds.62-66 Hammarlund and Sundberg67 published the only double-blind clinical trial that showed a significant benefit on ulcer healing however, this study did not include diabetic patients. Stone and Scott68 showed a greater limb-salvage rate in the HBO therapy-treated group (72% versus 53%), despite the HBO therapy-treated group having more serious wounds. Stone and Cianci are reportedly conducting a prospective, controlled, randomized, double-blind trial of HBO therapy for the treatment of diabetic foot wounds.69

Advanced technologies

Recent developments in wound care have made advanced technologies available for the treatment of diabetic foot ulcers. These include the Food and Drug Administration (FDA) approval of the tissue-engineered skin substitutes Graftskin (Apligraf; Organogenesis Inc, Canton, MA, and Novartis Pharmaceuticals Corporation, East Hanover, ND, and Interactive Wound Dressing (Dermagraft Advanced Tissue Science, La Jolla, CA, and Smith & Nephew, Largo, FL), as well as becaplermin (Regranex; Ortho-McNeil, Raritan, ND, a topical gel containing recombinant human platelet-derived growth factor. When used in conjunction with standard wound care techniques (including ongoing debridement, frequent dressing changes, pressure relief, and treatment of infection),70 these products have shown promise in treating diabetic foot ulcers. In addition, they may be helpful in managing diabetic ulcers that are unresponsive to standard therapy.

Apligraf gained FDA approval on June 20, 2000, for use in the treatment of noninfected diabetic foot ulcers (it had been previously approved for venous ulcers). A bilayered skin substitute, Apligraf is made from bovine collagen and cells derived from human infant foreskins. Apligraf contains living fibroblasts and keratinocytes that allow it to produce cytokines, growth factors, and matrix proteins associated with wound healing.71 Apligraf provides wound protection and fosters the growth of new skin. In a 4week study, Pham et alt used a regimen of standard wound care and weekly applications of Apligraf. Complete wound closure was obtained in 80% of the patients treated with Apligraf, compared with 42% of patients in the control group. Furthermore, the median time to complete closure in the patients receiving Apligraf was 42.5 days, compared with 91 days in the control group. Apligraf produced a higher healing rate in their patient population.