Oxandrolone for Management of Hypercatabolism in Severe Burns

Case

RG, a 69-year-old man, is admitted to the burn center for management following a 31% full thickness burn. A week into the admission, he begins to lose significant lean body mass (LBM). This symptom is thought to be a hypermetabolic response resulting from his burn. Pharmacy is consulted to assist with management.

Answer

Severe burn injuries cause a profound metabolic and catabolic response.¹ Initially there is a decrease in cardiac output and metabolism. However, after 48 hours, increased levels of endogenous catecholamines circulate, causing increased myocardial oxygen demand and a hypermetabolic response.^2,3 Insulin resistance quickly develops and there is not enough glucose available to meet metabolic demands. Skeletal muscle becomes a major source of fuel, leading to significant reductions in LBM. Compounding this issue, anabolic hormones, such as testosterone, are exceedingly diminished in severe burns. In the absence of testosterone, protein synthesis is decreased and body mass cannot be restored.² The inability to maintain LBM is detrimental in burn patients because it increases susceptibility to infection and impairs wound healing.^1,4

Oxandrolone, a synthetic derivative of testosterone, is used in patients with severe burns to increase LBM and enhance wound healing. It works by binding to intracellular androgen receptors, forming a complex which binds to DNA and stimulates protein synthesis.

Oxandrolone is preferred over testosterone based on its oral bioavailablity and low androgenicity, allowing it to be used in women and prepubescent children.² Wolf and colleagues evaluated the effect of oral oxandrolone 10 mg twice daily for 12 months beginning 5 days after injury and found a decrease in length of hospital stay.⁵ Additional studies found that oxandrolone was effective in maintaining LBM and improving bone density for an additional 3 to 5 years post therapy.^6,7 Hepatic enzymes were elevated in patients on oxandrolone, but no cases of hepatic damage were ever reported.^5-7

In the case of RG, oral oxandrolone 10 mg twice daily is recommended to prevent loss of LBM resulting from his burn. Treatment should be continued throughout his inpatient admission and rehabilitation. Liver function and blood lipids should be monitored periodically while on oxandrolone.

Jennifer Sutherland, PharmD, is a critical care pharmacist within the surgery group at University of North Carolina (UNC) Healthcare and an assistant adjunct faculty member at the UNC Eshelman School of Pharmacy.

References:

• Gauglitz GG, Williams FN, Herndon DN, Jeschke MG. Burns: where are we standing with propranolol, oxandrolone, rhGH, and the new incretin analogues? Curr Opin Clin Nutr Metab Care. 2011;14(2):176-181.
• Rojas Y, Finnerty CC, Radhakrishnan RS, Herndon DN. Burns: an update on current pharmacotherapy. Expert Opin Pharmacother. 2012;13(17):2485-2494.
• Wolfe RR. Review: acute versus chronic response to burn injury. Circ Shock. 1981;8(1):105-115.
• Pereira CT, Murphy KD, Herndon DN. Altering metabolism. J Burn Care Rehabil. 2005;26(3):194-199.
• Wolf SE, Edelman LS, Kemalyan N, et al. Effects of oxandrolone on outcome measures in the severely burned: a multicenter prospective randomized double-blind trial. J Burn Care Res. 2006;27(2):131-139.
• Jeschke MG, Finnerty CC, Suman OE, et al. The effect of oxandrolone on the endocrinologic, inflammatory, and hypermetabolic responses during the acute phase postburn. Ann Surg. 2007;246(3):351-360.
• Porro LJ, Herndon DN, Rodriguez NA, et al. Five-year outcomes after oxandrolone administration in severely burned children: a randomized clinical trial of safety and efficacy. J Am Coll Surg. 2012;214(4):489-502.