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Propranolol and Oxandrolone Therapy Accelerated Muscle Recovery in Burned Children.

ABSTRACT: INTRODUCTION:Severe burns result in prolonged hypermetabolism and skeletal muscle catabolism. Rehabilitative exercise training (RET) programs improved muscle mass and strength in severely burned children. The combination of RET with ?-blockade or testosterone analogs showed improved exercise-induced benefits on body composition and muscle function. However, the effect of RET combined with multiple drug therapy on muscle mass, strength, cardiorespiratory fitness, and protein turnover are unknown. In this placebo-controlled randomized trial, we hypothesize that RET combined with oxandrolone and propranolol (Oxprop) will improve muscle mass and function and protein turnover in severely burned children compared with burned children undergoing the same RET with a placebo. METHODS:We studied 42 severely burned children (7-17 yr) with severe burns over 30% of the total body surface area. Patients were randomized to placebo (22 control) or to Oxprop (20) and began drug administration within 96 h of admission. All patients began RET at hospital discharge as part of their standardized care. Muscle strength (N·m), power (W), V?O2peak, body composition, and protein fractional synthetic rate and fractional breakdown rate were measured pre-RET (PRE) and post-RET (POST). RESULTS:Muscle strength and power, lean body mass, and V?O2peak increased with RET in both groups (P < 0.01). The increase in strength and power was significantly greater in Oxprop versus control (P < 0.01), and strength and power was greater in Oxprop over control POST (P < 0.05). Fractional synthetic rate was significantly higher in Oxprop than control POST (P < 0.01), resulting in improved protein net balance POST (P < 0.05). CONCLUSIONS:Rehabilitative exercise training improves body composition, muscle function, and cardiorespiratory fitness in children recovering from severe burns. Oxprop therapy augments RET-mediated improvements in muscle strength, power, and protein turnover.

SUBMITTER: Chao T

PROVIDER: S-EPMC5820183 | biostudies-literature | 2018 Mar

REPOSITORIES: biostudies-literature

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Propranolol and Oxandrolone Therapy Accelerated Muscle Recovery in Burned Children.

Chao Tony T Porter Craig C Herndon David N DN Siopi Aikaterina A Ideker Henry H Mlcak Ronald P RP Sidossis Labros S LS Suman Oscar E OE

Medicine and science in sports and exercise 20180301 3

<h4>Introduction</h4>Severe burns result in prolonged hypermetabolism and skeletal muscle catabolism. Rehabilitative exercise training (RET) programs improved muscle mass and strength in severely burned children. The combination of RET with β-blockade or testosterone analogs showed improved exercise-induced benefits on body composition and muscle function. However, the effect of RET combined with multiple drug therapy on muscle mass, strength, cardiorespiratory fitness, and protein turnover are ...[more]

PMID: 29040226

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Project description:Administration of oxandrolone, a nonaromatizable testosterone analog, to children for 12 months following severe burn injury has been shown to improve height, increase bone mineral content (BMC), reduce cardiac work, and augment muscle strength. Surprisingly, the increase in BMC persists well beyond the period of oxandrolone administration. This study was undertaken to determine if administration of oxandrolone for 2 years yields greater effects on long-term BMC and bone mineral density (BMD). Patients between 0 and 18 years of age with ?30% of total body surface area burned were consented to an IRB-approved protocol and randomized to receive either placebo (n = 84) or 0.1 mg/kg oxandrolone orally twice daily for 24 months (n = 35). Patients were followed prospectively from the time of admission until 5 years postburn in a single-center, intent-to-treat setting. Height, weight, BMC, and BMD were recorded annually through 5 years postinjury. The long-term administration of oxandrolone for 16 ± 1 months postburn (range, 12.1-25.2 months) significantly increased whole-body (WB) BMC (p < 0.02) and lumbar spine (LS) BMC (p < 0.05); these effects were significantly pronounced for a longer time in patients who were in growth spurt years (7-18 years). When adjusted for height, sex, and age, LS BMD was found to significantly increase with long-term oxandrolone administration (p < 0.0009). Fewer patients receiving oxandrolone exhibited LS BMD z scores below -2.0 as compared with controls, indicating a significantly reduced risk for future fracture with oxandrolone administration. Long-term oxandrolone patients had significantly greater height velocity than controls throughout the first 2-year postburn (p < 0.05). No adverse side effects were attributed to the long-term administration of oxandrolone. A comparison of the current patients receiving long-term oxandrolone to previously described patients receiving 12 months of oxandrolone revealed that long-term oxandrolone administration imparted significantly greater increases in WB-BMC, WB-BMD, and LS-BMD (p < 0.05). In conclusion, the administration of oxandrolone for up to 24 months to severely burned pediatric patients significantly improves WB BMC, LS BMC, LS BMD, and height velocity. The administration of long-term oxandrolone was more efficacious than administration for 12 months. Additionally, fewer patients in the oxandrolone cohort met the diagnostic criteria for pediatric osteoporosis, pointing to a reduced risk for future bone fracture. This study demonstrates that administering oxandrolone for up to 2 years following severe burn injury results in greater improvements in BMC, BMD, and height velocity.

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Propranolol and Oxandrolone Therapy Accelerated Muscle Recovery in Burned Children.

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Propranolol and Oxandrolone Therapy Accelerated Muscle Recovery in Burned Children.

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