The Beneficial Effects of the Anabolic Steroid Oxandrolone in the Geriatric Burn Population

Introduction The geriatric patient, usually defined as being over 65 years of age, comprises an increasing percent of the major burn population.[1–3] This statistic will continue to increase as the aging population increases. The high morbidity and mortality in the geriatric burn population is related to the presence of significant comorbid factors, many of which decrease lean body mass and body protein content.[1–5] Some of these comorbid factors cannot be significantly improved, such as cardiopulmonary disease. However, one major comorbid factor, which appears to be increasing in the elderly, is the presence of a degree of protein energy malnutrition (PEM),[6–9] prior to the burn injury. This factor leads to lost lean mass, impaired immune function, thinning of skin, muscle weakness, and impaired healing. The addition of the anabolic steroid agent oxandrolone to optimum nutrition has been shown to decrease the rate of lean mass loss and increase the rate of restoration of lost weight in the general burn patient population. Oxandrolone should be especially beneficial in patients with pre-existing PEM once nutrition has been implemented.[10,11] However, the efficacy and safety of this approach has not been defined for the geriatric burn population. The purpose of this study was to determine the effect of the anabolic steroid oxandrolone in the geriatric burn population in a randomized prospective trial comparing standard of care versus standard care plus oxandrolone. Outcome variables measured included mortality, weight loss, nitrogen loss, and rate of wound healing, which are indicators of the status of the lean mass compartment. In addition, the authors wanted to assess length of stay, a marker of restoration of musculoskeletal function. The authors studied burns of 10 to 30 percent of total body surface, as this population is at high risk for morbidity. A burn of 10 percent or more is a major burn, especially in the geriatric population. Larger burns, exceeding 30-percent total body surface (TBS), have extremely high mortality in this age group mainly due to cardiopulmonary failure and infection and were not studied. Many of these larger burn patients deteriorate within hours after injury. Methods Study protocol. All burn patients over 65 years of age admitted to the burn center from 1999 through 2001 were eligible for this randomized prospective study, which was approved by the Institutional Research Review Board. Total body surface burn was required to be in the range of 10 to 30 percent of TBS with at least one excision and grafting procedure required. Exclusion criteria were an elevated prostate screening antigen (PSA) in male patients or patients with a history of prostate carcinoma. Patients enrolled were randomized into a burn care alone group or burn care plus oxandrolone 10mg/twice a day group. Patients with an elevated creatinine had a creatinine clearance performed. A dose of 10mg of oxandrolone a day was used if creatinine clearance was less than 25 percent of normal for age. The study was continued until the patient was discharged or transferred to our rehabilitation center. Oxandrolone was also discontinued if serum aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) exceeded three times normal values and remained elevated for over 72 hours in the absence of an identifiable cause. If values rapidly returned to normal, oxandrolone was re-instituted. Nutritional assessment and support. An assessment of nutritional status on admission was performed, which included a nutritional history, a history of pre-burn unintentional weight loss, especially over the previous six months, physical findings of malnutrition, and a serum pre-albumin level drawn immediately on admission. In addition, a standard hematology and chemistry profile was obtained at least weekly. Patients were defined as not being malnourished or having mild, moderate, or severe protein energy malnutrition, PEM, based on standard nutritional definitions, e.g., a pre-albumin of less than 5mg/dL was considered to reflect severe PEM. Measurements. Demographic and group descriptive data were obtained, which included age, gender, burn size, and burn depth in addition to other comorbid factors. Comorbid factors included presence of smoke inhalation injury, diabetes, cardiopulmonary disease, chronic illness, and the presence and degree of any PEM. Markers of outcome included death and infection complications, especially pneumonia. Burn wound infection was defined using the quantitative wound swab method. Markers of body composition changes included changes in weight from pre-admission weight. Pre-admission weight was determined by history if fluid resuscitation had started prior to admission. In addition, net nitrogen balance was obtained weekly as a marker of the degree of protein loss. A measurement of healing, a marker of anabolism, was the reepithelialization rate of the first donor site (10/1000 inch) taken in the surgical management of the deep burns. Complete reepithelialization was considered to be a healed wound. Also, length of stay per percent surface burn was considered a marker of the status of an anabolism and physical function. Statistical Analysis Between-group differences were determined using ANOVA. A p value of less than 0.05 was considered statistically significant. Results Of the 58 potential candidates, 50 patients were included. There were eight exclusions because of elevated PSA, none of which were eventually diagnosed as prostate cancer. There were four deaths in the study groups. There were two deaths in each group, all having burns over 25 percent of TBS with superimposed smoke inhalation injuries. The survival rate in both groups was significantly higher than that predicted for age and burn size from a national burn registry (Figure 1).[3] The demographics and characteristics of the two groups are shown in Table 1. Mean age was 70 years. Both groups had significant comorbid factors with an incidence of cardiopulmonary dysfunction of over 50 percent. Diabetes was also common. There was a significant incidence of PEM, exceeding half of the patients—a reflection of the health status of the elderly who suffer a burn. Most cases were mild to moderate in degree based on nutritional history, physical exam, and pre-albumin level. Anabolic markers. There was a significant decrease in the loss of body weight measured as percent of total (Table 2) and loss of body protein measured by nitrogen balance assessments (Figure 2) in the oxandrolone-treated group. In addition, there was a 30-percent decrease in the time to healing of a standard donor site in the oxandrolone group compared to the standard care group. Because there was no significant difference in any of the outcome variables assessed between the patients with pre-existing PEM and those without, the authors analyzed all variables using the entire group. Insufficient numbers to analyze subgroups was the reason that the authors could not do a subgroup analysis with severe PEM. Length of stay was significantly decreased in the oxandrolone group compared to control with both groups being significantly lower than predicted.[3] Since the time of discharge depended on the ability to function at home or in an acute rehabilitation facility, this comparison is a good reflection of preserved lean body mass (LBM) (Figure 3). Complications. Complication rates are presented in Table 3. As expected, pneumonia was the most common complication in this elderly group. All pulmonary complications resolved. Skin graft loss, defined as more than 15 percent of the graft being lost, is a marker of infection and also healing. Graft loss was significantly lower in the oxandrolone group. Mild liver dysfunction was seen in both groups with no differences in incidence. The mild liver dysfunction was transient and did not require stopping of the oxandrolone. There were no cases of progressive liver dysfunction. Discussion It has long been recognized that the increased morbidity and mortality in elderly burn victims is related as much to the presence of comorbid factors as to burn size.[1–7] The authors found, as would be expected, a high incidence of significant cardiopulmonary disease and diabetes in the study group. In addition, the authors noted an incidence of PEM, evidenced by pre-existing involuntary weight loss and decreased pre-albumin levels on admission, of nearly 50 percent of this group of geriatric patients.[7–9] The incidence of PEM is increasing in general in the elderly.[5–8] The added loss of body protein increases the risk of complications especially since a further loss of lean mass is expected from the burn.[1,2] Loss of LBM due to aging degeneration is a well-recognized risk factor for increased morbidity, especially impairment of musculoskeletal function, increased infection, and impaired healing.[7–9] As endogenous anabolic activity in the elderly population is quite low, a further loss of body protein due to the burn response will be more difficult to correct.[9,10] A decrease in protein synthesis will be evident.[9,10] The high incidence of some degree of pre-existing malnutrition in this population was an important finding.[9–11] Correction of a pre-existing malnourished state and correction of burn-induced weight loss is necessary to decrease morbidity. Many studies in the elderly population have demonstrated that correction of a lean mass deficit is not only important but it can be done quite effectively with the combination of a high-energy, high-protein intake, resistance exercise, which can be done at the bedside, and increasing anabolic activity, i.e., protein synthesis rate.[9–14] The authors have previously demonstrated that oxandrolone added to good nutrition decreases weight loss, improves wound healing, and more rapidly restores lean mass in burn patients 65 years of age and under.[10,11,15] In this study, it would appear that the addition of oxandrolone to the geriatric burn population also improves outcome. The authors noted a decreased morbidity defined as decreased weight loss, decreased nitrogen loss, increased healing rate, and decreased length of stay when oxandrolone was added to optimum nutrition.[1] Complications were minimal with mild transient increase in AST and ALT seen in 15 percent of patients in both groups with return to baseline in most cases even while on the agent.[12] Mortality (