Anabolic effects of oxandrolone in critically ill burn victims

Introduction: Severe burn causes a hypermetabolic, catabolic state. Loss of body protein, mainly from muscle, causes weakness, impaired immune function and delayed healing. Oxandrolone is an oral steroid that has been used in cachectic cancer and AIDS patients as well as rehabilitating burn patients to restore muscle mass. We hypothesize oxandrolone may reverse muscle catabolism in cachectic, critically ill burn patients. Methods: Ten severely burned children were enrolled in a prospective cohort analytic series. All had received care without skin grafting at outside hospitals prior to transfer to our pediatric burn unit. Upon transfer, excision and grafting and nutritional supplementation were employed. Nutritional status was assessed by weekly prealbumin measurements. Muscle protein kinetics were determined using a stable phenylalanine isotope tracer. Initial studies were done 5-7 days after admission. Six subjects were studied before and after approximately 1 week of oxandrolone 0.1 mg/kg QD. Four subjects were used as time controls and studied at matched time points. T-tests were used for statistical comparison. Data are presented as mean±SEM. Results: The four time control and six oxandrolone subjects did not differ in age or TBSA burn (7.1±3 yrs vs. 6.5±1.3 yrs; 40±5% vs. 41±11%). The control group arrived 34±17 days after injury, and the oxandrolone group 25±5. Prealbumin levels were low on presentation in both groups (9.3±3.8 mg/dl control vs. 7.4±2.8 oxandrolone) and remained low after one week of standard enteral feeding (14±5.3 vs. 13.3±2.2) with no differences between groups. Muscle protein net balance improved 1±6 nmol PHE/min/100cc leg in controls vs. 67±18 in the oxandrolone group (p<0.05). The improved protein metabolism in oxandrolone subjects was accompanied by an increased protein synthetic efficiency determined by the percent of intracellular amino acids directed to protein synthesis (17±6% before, 37±5% after oxandrolone; p=0.05). Muscle protein breakdown was unchanged. Conclusion: In cachectic, critically ill burn victims, oxandrolone improves net muscle protein synthesis by increasing the efficiency of intracellular amino acid utilization.