Improved Post-burn Hypertrophic Scarring and Physical Recovery with Year-long Administration of Oxandrolone and Propranolol
David N. Herndon1, Gabriel Hundeshagen*1, Austin F. Lee*2, Lewis E. Kazis*2, Jayson W. Jay*1, Guillermo Foncerrada-Ortega*1, Anesh Prasai*1, Amina El Ayadi*1, Evan Ross*1, Elizabeth Blears*1, Karel Capek*1, Christian Sommerhalder*1, Dagmar Amtmann*3, Kara McMullen*3, Robert Cox*1, Kristofer Jennings*1, Linda E. Sousse*1, Walter J. Meyer, III*1, Oscar E Suman*1, Celeste C Finnerty*1
1University of Texas Medical Branch, Galveston, TX;2Boston University, Boston, MA;3University of Washington, Seattle, WA
OBJECTIVE(S): Severe burns affect physical and psychosocial recovery through prolonged hypermetabolism, hypercatabolism, and inflammation. We previously demonstrated that administration of propranolol (Prop) or oxandrolone (Ox) during acute burn care ameliorate these effects. When co-administered for one year post-burn, growth is stimulated in severely burned children. We hypothesized that long-term administration of OxProp would decrease hypertrophic scarring and improve physical recovery over time. METHODS: Pediatric subjects (0-18 years) with ≥30% of total body surface area burned were randomized to placebo (n=254) or OxProp (n=62) administered for one year; patients were assessed for up to 3 years post-burn. Scar severity was evaluated with the Vancouver Scar Scale and biopsies examined histologically. The Burn Model Systems (BMS) Questionnaire and Shriners/ABA Burn Outcomes Questionnaire (BOQ) were administered at discharge from the ICU and at follow-ups. Mixed models using generalized estimating equations with random effects were used to generate 3-year recovery curves for each outcome domain and a composite score representing the physical component generated using factor analysis.
RESULTS: With OxProp compared to placebo: scar height and severity were reduced (p<0.05); histologically, nodularity (p<0.0001), dermal inflammation (p<0.0001), and abnormal procollagen deposition (p<0.0001) were decreased; skin tightness interfered less with physical function (p=0.003), and skin rigidity was reduced (p<0.05). The physical composite score improved over 36 months of post-burn recovery (p=0.016) with a large clinical effect (Cohen's d=2.4).
CONCLUSIONS: The novel co-administration of Oxandrolone and Propranolol for one year post-burn reduces hypertrophic scarring, and profoundly improves physical recovery of severely burned children.
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