Cilastatin

Chicago -- Wound bed preparation and surgical reconstruction of acute, intensive wounds can be improved with the use of artificial skin substitute and bFGF application prior to skin grafting, according to Sadanori Akita, M.D., Ph.D., senior assistant professor in the department of plastic surgery at Nagasaki University in Nagasaki, Japan.

"A dermal substitute such as Pelnac (Gunze Co.) provides a better wound bed in normally difficult wounds such as wounds over bones, tendons or poorly perfused tissues," Dr. Akita says. "The staged skin grafting, using a dermal substitute first and then a skin graft, allows the surgeon to use a thinner layer of donor skin to achieve the same grafted skin quality. As a consequence, donor-site morbidity is less severe."

At the 15th Annual Meeting of the Wound Healing Society, Dr. Akita presented clinical results of surgical reconstructions performed on a series of 10 critically ill patients with invasive necrotizing fasciitis.

The patients consisted of seven men and three women who ranged in age from 42 to 78 years (average 62.3 [+ or -] 13.50 years). Underlying diseases included idiopathic thrombocytopenic purpura, diabetes mellitus, impaired glucose tolerance, osteomyelitis, varicose veins and systemic lupus erythematosus. Six patients were infected with methicillin resistant Staphylococcus aureus (MRSA), two with group A streptococci, and two with group B streptococci. The wound was on a lower extremity in five cases, on the trunk in three cases, and on an upper limb in two cases. For one patient, surgical debridement was delayed for 48 hours after hospital admission, pending transfer to the surgical unit. For all other patients, extensive surgical debridement was performed immediately upon admission. All patients were treated with systemic antibiotics. Initial antibiotic treatment consisted of penicillin G (4.0 g per day) or imipenem and cilastatin sodium (1.0 g per day). If MRSA infections were detected, treatment was switched to vancomycin (1.0 g per day).

The skin substitute used was Pelnac, a bilayer that combines a porcine tendon-derived collagen sponge with an outer silicone membrane. Pelnac was applied to the wounds immediately after debridement, and injections of basic fibroblast growth factor (bFGF) underneath the bilayer membranes were given daily until the skin grafting was performed.

"Topical application of bFGF accelerates local vascularity, activates fibroblast proliferation and differentiation, and integrates circulating and local cells and various growth factors," Dr. Akita says. "In addition, bFGF application improves wound scars by modulating the scar formation process."

Recombinant human bFGF (Trafermin, Kaken Pharmaceutical Co.) was injected at a final concentration of 30 micrograms of bFGF per 6 [cm.sup.2]. None of the patients experienced local infections that necessitated the removal of the artificial dermis or change in the surgical planning. The artificial dermis was removed and a split-thickness skin graft was performed after an average of 17.5 days (range: nine days to 21 days). In all cases donor tissue was harvested from the thigh, and the average thickness of the skin graft was 0.009 [+ or -] 0.0019 inches (range: 0.006 to 0.012 inches). The mean follow-up period after the final surgery was 3.6 [+ or -] 2.27 years (range: one to 7 years).

Measurements of skin hardness at the scar site were performed using a Teclock GS-701N durometer (Tedock Co.) according to the manufacturer's instructions. Five measurements were made at each of three points at least 6 mm apart and 12 mm from the edge of intact skin. Similar measurements were made in normal skin and in scar tissue from wounds not treated with bFGF.

Mean skin hardness in healthy volunteers, measured in various anatomical locations such as trunk, buttock, upper limb, thigh and calf, was 6.3 [+ or -] 1.75. Mean skin hardness of the scar tissue from the 10 bFGF-treated patients was 7.9 [+ or -] 3.64, comparable to normal skin and significantly lower than the measurement of 15.5 [+ or -] 4.39 in scar tissue from non-bFGF-treated wounds. These results suggest that bFGF treatment may improve the skin texture in wound healing.

"There were no obvious side effects using the dermal substitute, but larger wounds showed severe post-surgical deformities, probably induced by damage to the venous and lymphatic drainage," Dr. Akita says. "Because only a thin layer of donor skin was needed in the graft, the donor-site morbidity was minimal."

Dr. Akita and colleagues recommend the use of artificial dermis and bFGF injections for wound bed preparation prior to skin grafting in surgical reconstruction of invasive necrotizing fasciitis or similar difficult wounds.

Disclosure: Dr. Akita reports no conflicts of interest.

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