Disclosures: Dr. Demling is on the speakers bureau of BTG Pharmaceuticals Inc.

Introduction

Necrotizing fasciitis is defined as a necrotizing nonclostridial soft-tissue infection spreading along fascial planes.[1–6] The thrombosis of local blood vessels leads to devascularization and necrosis of overlying subcutaneous tissue and skin. The infection is usually caused by a combination of Gram-positive and Gram-negative aerobic and anaerobic organisms.[1–6]

After early aggressive surgical debridement has been performed, a large open wound results, which often takes several weeks to months to close. The combination of a large wound and residual soft-tissue inflammation should lead to a profound catabolic state comparable to a severe burn resulting in a loss of lean body mass. Lost body protein can lead to an immune deficiency state, weakness, and impaired wound healing.[7–10] Although healthy patients can develop this disorder, a comorbid factor, such as diabetes, is often present.[11]

The anabolic steroid, oxandrolone, has been shown to decrease catabolism and significantly attenuate lost lean mass after burn injury and other severe wounds.[12–14] There are currently no studies on the degree of the catabolic response to necrotizing fasciitis or on the effect of adding an anabolic steroid to this process.

The authors’ purpose was twofold. The authors first wanted to determine the degree and time course of catabolism, weight loss, and wound healing rate in patients with necrotizing fasciitis. Secondly, the authors wanted to determine the effect of adding the anabolic steroid, oxandrolone (Oxandrin®, BTG Pharmaceuticals, Inc., Iselin, New Jersey), to nutritional support and aggressive debridement on parameters measuring the rate of catabolism.

Methods

Study protocol. Patients over 18 years of age with the diagnosis of acute necrotizing fasciitis were eligible for the study. Age, sex, and presence of diabetes or other chronic disease were identified. Also identified was the initial site of the necrotizing fasciitis. On admission, patients were randomized into a standard care or standard care plus oxandrolone group. All patients were initially fluid resuscitated, begun on imipenem-cilastatin 1gm every six hours, underwent an initial surgical debridement, and then were begun on nutritional support. Caloric intake was determined using indirect calorimetry, and protein intake was determined to be 1.5g/kg/day. Nutrition was provided by the oral route using a small nasogastric feeding tube to provide the high-calorie, high-protein intake. All patients were given their assessed nutrient needs.

On Day 4 when nutritional support had been initiated, patients were treated either with standard care or standard care plus oxandrolone 20mg/day in two divided doses until wound closure was complete. Exclusion criteria for this Institutional Review Board-approved study was the presence of an elevated prostate-specific antigen (PSA), as prostate cancer is considered a contraindication for the use of oxandrolone.

The microbiology of the wound was identified through biopsies obtained on the initial and subsequent debridement, as well as the site of involvement. Gram stains of the biopsies, which included the involved soft tissue and fascia, were also obtained. The need for further debridement of involved tissue was based on daily clinical assessment of the open wound.

Local wound care consisted of daily dressing changes consisting of moist gauze dressings on the wound surface. Debridement was performed with the changes of the gauze, as well as local sharp debridement. This approach was used until all necrotic tissue was removed and there was no evidence of remaining infection. The clean wound was then managed using a closed drainage system (vacuum-assisted closure, V.A.C.®, Kinetic Concepts, Inc., San Antonio, Texas) until the wound was ready for closure.