Mrs B, 78, is admitted to a wound center with a large sacral wound and a fever of 103°F. Clinical assessment of the patient reveals a Stage IV pressure ulcer measuring 4.3 x 7 cm, 2 cm deep, with undermining of 1 cm laterally along 1 complete edge. Approximately 60% of the wound surface is covered with hard, necrotic tissue, and 25% with yellow slough.
A complete history and physical, neuropsychological examination, and nutritional assessment are obtained. The latter includes anthropometric measurements, biochemical analysis of parameters indicative of nutritional status, and calculation of Mrs B’s overall nutrient and fluid requirements. Table 1 lists the results of the nutritional assessment. Table 2 reviews common laboratory markers of nutritional status.
Before deciding on any course of treatment for this patient, the practitioner needs to understand how the treatment works and the rationale behind it. In the case of patients with nonhealing cutaneous wounds, one must first understand the body’s physiologic response to a wound and how supplemental nutritional and pharmacologic therapies may attenuate this response.
The Stress Response
When the body is under stress, whether physical or psychological, its fight-or-flight mechanism is amplified. The initial insult leads to local and generalized inflammation and an increase in the level of stress hormones, particularly catecholamines and cortisol. 1 At the same time, the body experiences a decrease in the level of anabolic hormones (human growth hormone and testosterone). This hormonal imbalance leads to a catabolic and hypermetabolic state, in which the body breaks down to release energy to meet increased demands. Working harder and faster than usual to fight off the stressor and regain homeostasis causes both body temperature and metabolic rate to increase. This leads to an increased demand for glucose, which may be met by gluconeogenesis or rapidly breaking down lean body mass as a means of obtaining more energy.
Loss of Lean Body Mass
If this cycle continues for an extended period, a patient will lose weight and, more important, experience a loss of lean body mass. Table 3 shows the effects of continued loss of lean body mass. If a patient shows a steady downward trend in body weight, his or her body will lack sufficient energy and nutritional substrate from which to build new tissue to heal a wound. Building new tissue requires protein to fuel an anabolic process. A stressed, catabolic patient will lack this protein because it will be shuttled off the normal metabolic course to be used for energy. In other words, healing is an anabolic process.
Weight loss and lean body mass loss are symptoms of a catabolic process. A patient cannot be in anabolic and catabolic states simultaneously. Wound healing will likely be delayed until the weight loss and catabolic process are corrected.
Therefore, management of this patient is a multifaceted process designed to correct impaired healing and weight loss. 2 Specific goals for practitioners treating patients in this case include:
- controlling the catabolic state
- restoring sufficient nutrient intake to meet increased protein and energy needs
- maintaining protein intake at approximately 1.5 g/kg/day to allow for restoration of lost lean body mass
- increasing anabolic stimulation to direct protein intake into protein synthesis
- avoiding replacement of lost lean body mass with fat gain
- using resistance exercise to increase the body’s anabolic drive
- considering the use of exogenous anabolic hormones to increase net protein synthesis.
Course of Treatment
Antibiotics and appropriate acute medical care are initiated for Mrs B. The surgical wound team debrides and excises the wound within 3 days. An absorbent wound dressing is chosen for its ability to manage the flow of exudate and facilitate autolytic debridement of the slough and necrotic tissue. Once Mrs B is stabilized, she is transferred to a long-term-care facility for further wound care, antibiotics, and preparation for grafting.
Nutritional status should be optimized, as measured by an albumin level of at least 3.5 g/mL prior to flap reconstruction. 3 In conjunction with frequent turning and repositioning to alleviate pressure to the sacral area, nutritional support, including a high-protein supplement, is initiated. The patient is given her favorite foods and a daily multivitamin and vitamin C and zinc supplements. To meet her elevated nutritional needs, a between-meals supplement program is started. Several different supplements are tried until the patient’s favorites are identified. Many choices are available for high-protein supplements, including canned liquid drinks, shakes, puddings, cookies, high-protein coffee, and protein powder that can be mixed with a variety of foods and beverages. The various types should be offered to a patient until an acceptable flavor and texture is found. For this patient, the practitioner initiated a routine of pudding in the morning, a shake in the afternoon, and cookies at bedtime. Variety is important in any supplementation program to avoid food and flavor fatigue.
To increase anabolism and restore lost lean body mass, the practitioner orders oxandrolone (Oxandrin), 5 mg orally every 12 hours. The testosterone analog oxandrolone attenuates the catabolic state by decreasing protein breakdown and increasing protein synthesis. 4 This also improves intracellular reutilization of amino acids so that nitrogen is retained in the body rather than excreted. 4 A successful effort has been made to separate the anabolic activity from the androgenic or virilizing activity of testosterone, leading to fewer adverse effects.
Oxandrolone has 6.3 times more anabolic activity than methyl testosterone. 5 The drug is the only oral agent approved by the Food and Drug Administration to promote weight gain after involuntary weight loss due to surgery, chronic infections, or severe trauma or for any patient who fails to maintain normal weight. It is also approved to offset the protein catabolism associated with prolonged corticosteroid use. 6
Several studies have been conducted using oxandrolone in a variety of patient populations, including patients with spinal cord injuries, burns, cancer, and HIV/AIDS. 7–10 Demling and DeSanti studied the relationship between restoration of weight loss and wound healing. 11 The study subjects had nonhealing wounds for an average of 12 months, despite good local wound care. All subjects had lost 10% or more of their usual body weight and did not regain lost weight, despite optimal nutritional intervention. Oxandrolone was added to the treatment regimen for a 12-week period. The authors reported a significant correlation between weight restoration and wound healing, with the most significant wound healing occurring after 50% of the lost weight had been restored.
After 3 weeks of nutritional intervention, Mrs B’s albumin level is 3.0 g/mL and her prealbumin level is 18 mg/mL; she has gained 4 pounds. Her wound has developed significant granulation tissue, with little evidence of infection. One week later, the patient undergoes a complex flap procedure, and 7 days later, she is discharged with a total weight gain of 6 pounds and a prealbumin level of 21 mg/mL. The sacral pressure ulcer is covered with a viable flap.
Wound healing and involuntary weight loss are interrelated clinical problems. To optimize wound healing, the practitioner should examine and document the reasons that a patient continues to lose weight. If weight loss continues despite attempts to maximize nutritional intake and optimize the patient’s diet, a hormonal imbalance due to a stress response may be the cause.
This case demonstrates that the combination of nutritional support, including nutrient supplementation, and the anabolic agent oxandrolone can lead to a significant improvement in wound healing and, ultimately, a viable graft. The correction of involuntary weight loss with appropriate nutritional support and the anabolic stimulus provided by oxandrolone can accelerate wound healing by reversing lean body loss, thus improving a patient’s outcome.
1. Himes D. Protein-calorie malnutrition and involuntary weight loss: the role of aggressive nutritional intervention in wound healing. Ostomy Wound Manage 1999; 45:46–55.
2. Demling RH, DeSanti L. Protein-energy malnutrition and the nonhealing cutaneous wound. Medical Education Collaborative/Medscape Online Clinical Module. Available at http://www.medscape.com/viewprogram/714_pnt
. Accessed November 14, 2003.
3. Wilhelmi BJ, Neumeister M. Pressure ulcers, surgical treatment and principles. Available at http://www.emedicine.com/plastic/topic462.htm
. Accessed November 14, 2003.
4. Sheffield-Moore M, Urban RJ, Wolf SE, et al. Short-term oxandrolone administration stimulates net muscle protein synthesis in young men. J Clin Endocrinol Metab 1999; 84( 8): 2705–11.
5. Fox M, Minot AS, Liddie GW. Oxandrolone: a potent anabolic steroid of novel chemical configuration. J Endocrinol Metab 1962; 22:921–4.
6. Oxandrin (oxandrolone) Package Insert. Savient Pharmaceuticals. New Brunswick, NJ. 2001.
7. Spungen AM, Koehler KM, Modeste-Duncan R, Rasul M, Cytryn AS, Bauman WA. 9 clinical cases of nonhealing pressure ulcers in patients with spinal cord injury treated with an anabolic agent: a therapeutic trial. Adv Skin Wound Care 2001; 14:139–44.
8. Demling RH, DeSanti L. Use of anticatabolic agents for burns. Curr Opin Crit Care 1996; 2:282–91.
9. Strawford A, Barbieri T, Van Loan M, et al. Resistance exercise and supraphysiologic androgen therapy in eugonadal men with HIV-related weight loss: a randomized controlled trial. JAMA 1999; 281:1282–90.
10. Cleary S. Ongoing placebo-controlled study of oxandrolone in cancer-related weight loss. Abstract 1039. Presented at the 44th Annual Meeting of the American Society for Therapeutic Radiology; October 19–23, 2003; Salt Lake City, UT.
11. Demling R, De Santi L. Closure of the “non-healing wound” corresponds with correction of weight loss using the anabolic agent oxandrolone. Ostomy Wound Manage 1998; 44:58–68.