Anabolic Steroid Hastens Wound Healing (Following Burns)
Anabolic Steroid Hastens Wound Healing (Following Burns)
Abstract & Commentary
Synopsis: Following severe burn injury, patients given the testosterone analog oxandrolone demonstrated improved nitrogen retention and more rapid donor skin graft site healing than control patients receiving a placebo.
Source: Demling RH, Orgill DP. J Crit Care 2000;15:12-17.
Burns are associated with significant catabolism, and survival may be improved by modifying this deleterious response with anabolic steroids. Twenty patients with at least 40% deep body surface burns, requiring at least 20% body surface skin grafting, were randomized to receive either 20 mg/d of oxandrolone (OX) or placebo (PL) in two divided doses by mouth or by tube, starting by day three and continuing until transfer to a rehabilitation center. In addition to burn area, metabolic rate was measured every three days, nitrogen balance was measured weekly, body weight gain was charted daily, and donor skin site wound healing rate was observed every other day starting five days after harvest. Liver function abnormalities were used to identify possible drug toxicity. A standard feeding formula was used in both groups. Most nutrition was provided by the enteral route. Time to discharge to a rehabilitation center was used as length of stay.
Eleven patients received the treatment drug and nine received placebo. The groups were well matched in age (49 ± 13 OX; 44 ± 6 PL) and in burn size (54 ± 9% OX; 49 ± 7% PL), and about half the patients in each group had an inhalation injury as well. Metabolic rate was increased in both groups by about 50% and was not different at any point. Daily nitrogen balance was much less negative in the OX group, averaging less than half of the PL group on every measurement until discharge. Body weight declined less (after the second week) in the OX group. Donor wounds healed an average of four days sooner in the OX group (9 vs 13 days). While the average time to discharge was less in the OX group (29 vs 35 days), the large variation in the small sample did not produce a statistical difference in discharge time. About half of each group developed liver function abnormalities, but none was considered significant enough to stop the treatment. No patient developed abnormal hair growth.
COMMENT BY CHARLES G. DURBIN, Jr., MD, FCCM
While this is a small group of patients with a specific problem, the results are promising enough to consider expanding the test groups to include patients with acute respiratory distress syndrome (ARDS) and other inflammation-mediated diseases. The maintenance of body weight and improved wound healing seen in the present study were impressive. While not specifically evaluated, much of the improvement was probably in preservation of muscle mass. If this same protection occurs in the diaphragm, significant outcome benefit could be obtained, resulting in reduced weaning times in patients requiring mechanical ventilation. Failure to reduce length of stay in this study is merely due to the small number of patients studied.
Growth hormone has been used to promote tissue healing, but unlike this androgenic steroid, it seems to significantly increase metabolic rate as well as to disrupt glucose metabolism. Whether the failure to see an increase in metabolic rate from OX is related specifically to treatment of burns or is true in other forms of critical illness remains a question to be answered. The use of anabolic steroids is approved to help restore muscle mass following critical illness, but this is the first convincing study demonstrating benefit when administered during the illness. The safety of this agent is suggested but not proved by this study.
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