The rate of restoration of body weight after burn injury, using the anabolic agent oxandrolone, is not age dependent.

We determined the effect of age on the restoration of lost body weight and lean mass after burn injury, using the anabolic steroid oxandrolone. Patients with deep burns of 30-55% of body surface were studied when entering the recovery phase of injury, defined as resolution of the hypermetabolic, catabolic state. Patients were provided optimum nutrition and exercise alone or with the addition of oxandrolone. The rate of body weight and lean mass gain and improvement in physical function were measured over a 4-week period. Four groups were studied. A younger group, mean age of 34 years and burn size of 47+/-7% versus an older group, mean age 60 years and burn size 36+/-5%. The mean loss of body weight in the younger and older groups was 10+/-2 and 11+/-2% of total. Both groups were randomly divided into a control and oxandrolone study group. Weight restoration, 74+/-5% of which was lean mass, averaged 1.7+/-0.4 kg and 1.6+/-0.3 kg per week in the young and older oxandrolone groups. This rate was compared with 0.7+/-0.2 kg and 0.5+/-0.2 kg in the young and older control groups, with only 55% of weight gain being lean mass. These differences were statistically significant. The increase in the rate of weight gain with oxandrolone corresponded with a 30% decrease in length of stay in the burn rehabilitation unit. We concluded that the ability of an anabolic steroid to restore lean mass and physical function after burn surgery is not related to age.

Effect of a hypocaloric diet, increased protein intake and resistance training on lean mass gains and fat mass loss in overweight police officers.

We compare the effects of a moderate hypocaloric, high-protein diet and resistance training, using two different protein supplements, versus hypocaloric diet alone on body compositional changes in overweight police officers. A randomized, prospective 12-week study was performed comparing the changes in body composition produced by three different treatment modalities in three study groups. One group (n = 10) was placed on a nonlipogenic, hypocaloric diet alone (80% of predicted needs). A second group (n = 14) was placed on the hypocaloric diet plus resistance exercise plus a high-protein intake (1.5 g/kg/day) using a casein protein hydrolysate. In the third group (n = 14) treatment was identical to the second, except for the use of a whey protein hydrolysate. We found that weight loss was approximately 2.5 kg in all three groups. Mean percent body fat with diet alone decreased from a baseline of 27 +/- 1.8 to 25 +/- 1.3% at 12 weeks. With diet, exercise and casein the decrease was from 26 +/- 1.7 to 18 +/- 1.1% and with diet, exercise and whey protein the decrease was from 27 +/- 1.6 to 23 +/- 1.3%. The mean fat loss was 2. 5 +/- 0.6, 7.0 +/- 2.1 and 4.2 +/- 0.9 kg in the three groups, respectively. Lean mass gains in the three groups did not change for diet alone, versus gains of 4 +/- 1.4 and 2 +/- 0.7 kg in the casein and whey groups, respectively. Mean increase in strength for chest, shoulder and legs was 59 +/- 9% for casein and 29 +/- 9% for whey, a significant group difference. This significant difference in body composition and strength is likely due to improved nitrogen retention and overall anticatabolic effects caused by the peptide components of the casein hydrolysate.

Enteral glutamine administration prevents the decrease in cell energy charge potential produced in ileum after a skin burn in the rat.

A skin burn produces a decrease in cell energy charge potential (ECP), a marker of cell function, in the liver and other organs. The process appears to be oxidant induced because reduced glutathione (GSH) appears to be protective. The gut mucosal barrier is also known to be altered after burns and appears to be improved by glutamine, which is a source of energy and GSH production. Neither the relationship between the gut barrier change and the ECP of the gut barrier nor the mechanism of glutamine protection has been defined. The effect of a 20% total body surface area, full-thickness burn in a rat on ECP and GSH content in the ileum and the liver and the effect of oral glutamine (1 g/kg/d) on any changes were studied. Three groups of rats (14 rats per group) were studied: a control group, a group with burns alone, and a group with burns that were given glutamine. Half of the rats were killed 1 day after the burn, and the other half were killed 6 days after the burn. ECP did not decrease 1 day after the burn, but 6 days after the burn, ECP decreased from a control of 0.53+/-0.06 to 0.41+/-0.01 in the liver and from 0.64+/-0.04 to 0.29+/-0.04 in the ileum. In the ileum, glutamine prevented the decrease of the ECP (which increased to 0.58+/-.03), but in the liver, glutamine did not alter the ECP (which remained at 0.42+/-0.05). The GSH content was unchanged after the burn injury in both organs compared with the value before the burn injury. It can be concluded that a delayed decrease in ECP in the ileum occurs after a burn injury. Orally administered glutamine prevents the decrease in ECP, probably by providing cell energy rather than by increasing gut GSH (antioxidant) activity.

Oxandrolone, an anabolic steroid, enhances the healing of a cutaneous wound in the rat.

The effect of the anabolic steroid oxandrolone on the healing rate of a standardized full thickness linear wound on the back of the rat was studied. Oxandrolone was given orally by gavage in peanut oil at a dose of 0.1 mg/kg/day. A placebo powder in peanut oil was given at the same dose to a control group. Parameters monitored were time to complete wound closure, wound hydroxyproline content and tensile strength, as well as histology. We found that wounds closed completely in 12+/-3 days with oxandrolone, compared to 18+/-3 days for a placebo, a statistically significant difference. The rate of body weight gain was identical in both groups. Hydroxyproline content of the healed incision site was 23+/-4 mg/g tissue vs. 17+/-3 mg/g tissue, while the tensile strength increased to 185+/-13 g/mm2 vs. 102+/-18 g/mm2 in the oxandrolone and placebo groups, respectively. Both parameters were significantly increased with the anabolic steroid. Histologic examination showed a wound that contained more mature and densely packed collagen and was also hypercellular with oxandrolone treatment. We conclude that the anabolic steroid oxandrolone significantly enhanced wound healing unrelated to any generalized increase in protein mass as would be reflected in body weight.

The anticatabolic and wound healing effects of the testosterone analog oxandrolone after severe burn injury.

PURPOSE: Severe burn injury leads to marked catabolism and decreased lean mass, which can impair healing. Anabolic agents can attenuate net catabolism. Our purpose was to determine whether the testosterone analog, oxandrolone, given during the acute post burn period decreased the degree of nitrogen loss and loss of body weight while also increasing the healing rate of a skin donor site. MATERIALS AND METHODS: Patients with burns between 40% and 70% of body surface were studied. A randomized double-blinded placebo-controlled study design was used. Patients were given oxandrolone 20 mg/day (n = 11) or a placebo 20 mg/day (n = 9) beginning between days 2 and 3 post burn. Net nitrogen balance and the healing time of a standardized donor site were measured. Patients were monitored until transferred to a burn rehabilitation facility, an average time period of 33 +/- 9 days. RESULTS: Mean burn size was 49 +/- 8% for placebo and 53 +/- 9% of total body surface for the oxandrolone group. Smoke inhalation was present in approximately 50% of patients in both groups. All patients survived the burn injury. Net weight loss was 8 +/- 3.1 kg in the placebo group compared with 3 +/- 1.9 kg in the oxandrolone group, a statistically significant decrease. Net daily nitrogen loss over a 3-week period (days 7 to 28) was 13 +/- 4 g in placebo treated compared with 4 +/- 1.9 g for the oxandrolone group, a statistically significant decrease. The healing time of a standardized donor site, decreased from the placebo group value of 13 +/- 3 days to 9 +/- 2 days for oxandrolone treated patients, a significant improvement. No major liver dysfunction, or other complication attributable to an anabolic steroid was seen in either group. CONCLUSION: We found the anabolic agent, oxandrolone, significantly decreased weight loss and net nitrogen loss and increased donor site wound healing compared with placebo controls. We noted no complications with the use of oxandrolone.

Metabolic management of patients with severe burns.

Burn injury results in profound metabolic abnormalities perpetuated by an exaggerated stress response to injury. Hypermetabolism and marked catabolism, with rapid erosion of lean body mass, becomes evident shortly after injury. Much of the morbidity and mortality of a major burn can be attributed to this process, which increases infection risks, decreases the healing rate, and alters cell function. Rapid removal of devitalized burn tissue combined with early aggressive nutritional support significantly attenuates this autodestructive process. The addition of anabolic agents decreases the degree of lean mass loss and increases the rate of restoration. Immediate attention to the metabolic response to a severe burn significantly decreases complications and improves outcome.

Involuntary weight loss and the nonhealing wound: the role of anabolic agents.

Endocrine responses to trauma result in a net catabolic state and exaggerated hepatic gluconeogenesis, with losses in lean body mass that can compromise wound healing. With proper nutrition, reduction of stress, resistance exercise, and the addition of certain anabolic agents, lean body mass can be restored and wound healing promoted.

Comparison of the anabolic effects and complications of human growth hormone and the testosterone analog, oxandrolone, after severe burn injury.

This study compared the anticatabolic and wound healing effects of the anabolic agents human growth hormone, HGH, and the testosterone analogue, oxandrolone, after severe burn injury. A randomized prospective study design was used. Patients were given HGH at a dose of 0.1 mg/kg/day (n = 20) or oxandrolone, 20 mg/day (n = 16), beginning between days 7-10 post-burn. Data was compared to burn patients not placed on either agent (n = 24). Patients were monitored until they were sufficiently healed to be transferred to a rehabilitation center. The results of our study were as follows. All patients survived. Net weight loss was 8 +/- 2.1 kg in the control group compared with 4 +/- 1.8 kg with HGH and 3 +/- 1.2 kg with oxandrolone, a significant decrease. Net daily nitrogen loss was 12 +/- 3 g in non-treated compared to 3 g or less for each of the anabolic groups, a significant decrease. The metabolic rate in untreated burns was 155 + 25% of predicted normal, compared to 178 +/- 28% for HGH and 156 +/- 20% for oxandrolone treated patients. The complete healing time of a standardized donor site, decreased from the control value of 14 +/- 2 days to 10 +/- 3 days for HGH and 10 +/- 2 days for oxandrolone treated patients, a significant improvement. Hyperglycemia (glucose over 225 mg/dl 12.5 mM) was present in 100% of HGH patients compared to 55% for control and 50% for oxandrolone treated. We found that both anabolic agents significantly decreased weight and nitrogen loss and increased healing with nearly identical benefits. However HGH resulted in the significant complications of hyperglycemia and accentuated hypermetabolism. We noted no side effects with oxandrolone.

Management of partial thickness facial burns (comparison of topical antibiotics and bio-engineered skin substitutes).

This study compared the effect of standard topical antibiotic management versus a biological skin substitute wound closure for mid-partial thickness burns of the face. Adult patients with mid-dermal facial burns produced by flash flames or flame exposure were studied using a randomized prospective study design. Total daily burn care time, pain (0-10 scale) and healing time were monitored. Immediately after partial thickness debridement, the entire face burn, including ears, was closed with a bioengineered skin substitute coated with fibronectin (TransCyte) or treated by the open technique using bacitracin ointment applied 2-3 times daily. 21 patients were studied, with 10 patients in the skin substitute group. We found a significant decrease in wound care time 0.35 +/- 0.1 versus 1.9 +/- 0.5 h, decrease in pain of 2 +/- 1 versus 4 +/- 2 and re-epithelialization time 7 +/- 2 versus 13 +/- 4 days in the skin substitute group compared to topical antibiotics. We can conclude that a bioengineered skin substitute significantly improves the management and healing rate of partial thickness facial burns, compared to the standard open topical ointment technique.

Anticatabolic and anabolic strategies in critical illness: a review of current treatment modalities.

Critically ill patients characteristically exhibit a pronounced catabolism in addition to a down-regulation of normal anabolic activity, leading to major complications from loss of body protein stores. The marked decrease in lean body mass and protein stores leads to the loss of essential structural and functional proteins required for restoring and maintaining homeostasis. The standard management of the catabolic response to injury and illness has centered on optimizing nutrient intake that modulates but does not reverse the process. Complications of ongoing catabolism therefore remain a major cause of morbidity. Addition of anticatabolic and anabolic agents that may counteract "the stress response to injury or illness" may be of significant clinical benefit. Agents currently available for clinical use, which will be described, can be divided into two groups. The first group are nutrients and nutrient metabolites, namely protein and the specific amino acids, glutamine, arginine, and branched chain amino acids, especially leucine. The second group are anabolic hormones, namely growth hormone, testosterone, and the testosterone analog oxandrolone. The pros and cons of these agents, as to their anabolic and anticatabolic value, are described.

Increased protein intake during the recovery phase after severe burns increases body weight gain and muscle function.

We determined the effect of protein intake on weight gain and muscle function in the recovery phase after severe burns. Fifteen patients with deep burns between 30% to 50% of total body surface were studied over a 3 week period-after resolution of the hypermetabolic, catabolic state. All patients were studied in an acute rehabilitation hospital affiliated with the burn center. Nutritional profiles; weight gain; and muscle strength, measured by a physical therapy index (0 to 10)--10 being the greatest progress-were measured. All patients were provided a high-calorie, high-protein diet. Group 1 patients (n=8) also were provided a standard nutrient supplement to maintain caloric intake at 30 to 35 kcal/kg/day and to maintain protein intake at 1.3 to 1.5 g/kg/day. Group 2 patients (n=7) were provided a high-calorie, high-protein diet plus a protein hydrolysate (70 g/day) that provided a protein intake of 1.7 to 2 g/kg/day. Group 1 patients averaged a 1 to 1.5 pound weight gain per week or four pounds during three weeks. Their physical therapy index at three weeks of 4+/-0.5 indicated adequate improvement in strength and endurance. Group 2 patients averaged 2.5 to 3 pounds weight gain per week or 8.5 pounds during three weeks. Their physical therapy index of 7+/-0.7 indicated marked gains in muscle strength. Both measurements were significantly higher than those of Group 1. We conclude that increased protein intake by means of adding a protein hydrolysate increases the rate of restoration of body weight and muscle function.

Oxandrolone, an anabolic steroid, significantly increases the rate of weight gain in the recovery phase after major burns.

We studied the effect of an anabolic steroid, oxandrolone, combined with a high-protein diet (2 g/kg/day) on the rate of weight gain and restoration of muscle function in the recovery phase after deep burns of 30 of 50% of total body surface (n = 7). The findings were compared with findings from an isocaloric (2 g/kg/day protein) diet alone (n = 6). The study was prospective and randomized. Data were also compared retrospectively with data from a group of burn patients treated in the same fashion using a high-calorie, high-protein diet with a protein content of 1.3 to 1.4 g/kg/day (n = 10). Muscle function was quantified using a physical therapy index defining rate of progress (0 = lowest, 10 = highest). Oxandrolone was given in the beginning of the recovery phase in a dosage of 10 mg orally twice a day. The recovery phase was defined as resolution of the hypermetabolic state using physiologic criteria. The study was performed in an acute burn rehabilitation facility where patients were transferred once entering the recovery phase. Patients in each group were not different with regard to age and burn size. We found that mean weight loss for all patients was 11 +/- 2% of preburn weight during the catabolic phase despite optimum nutrition and early wound closure. Data are presented as mean +/- SD. We found that the average weight gain during the first 3 weeks was 14.5 +/- 2.5 pounds and that the physical therapy index was 8.8 +/- 0.5 of recovery in the oxandrolone-protein group (n = 7); both of these values were significantly greater than the corresponding values in the other groups. In the high-protein alone group (n = 6), weight gain was 7.5 +/- 1.7 pounds and physical therapy index was 7.0 +/- 0.8. In the retrospective group (n = 10), weight gain was 4.4 +/- 0.8 pounds and function index was 4.1 +/- 0.5. The daily caloric intake was not different between groups. Protein content and oxandrolone were the variables. No side effects were noted with oxandrolone. We can conclude that an anabolic steroid combined with increased protein intake can significantly increase the rate of restoration of weight gain postburn.

Excessive liver oxidant stress causes mortality in response to burn injury combined with endotoxin and is prevented with antioxidants.

We studied the effect of the oral administration of a water-soluble antioxidant solution containing ascorbic acid, glutathione, and a precursor for glutathione synthesis, N-Acetyl-L-cysteine, on liver antioxidant activity, liver cell energetics, and mortality in rats in response to a 20% third-degree burn injury challenged 5 days later with an intraperitoneal injection of 30 mg/kg endotoxin. Rats with burns were fluid-resuscitated with subcutaneous Ringer's lactate solution according to the Parkland formula (4 cc/kg/%burn). Rats challenged with endotoxin 5 days after burn were given an additional 100 ml/kg of subcutaneous Ringer's lactate solution immediately after the injection of endotoxin. A group of rats with burns challenged with endotoxin 5 days after burn were given an oral antioxidant solution beginning after burn injury. Liver cell energetics were measured as tissue energy charge potential (ECP), adenosine triphosphate (ATP) content, and total adenine nucleotides. The levels of endogenous liver glutathione, catalase, vitamin C, and vitamin E were measured to monitor antioxidant status. We found that burn injury alone did not produce any mortality over the 6-day period despite a 35% decrease in liver energy charge potential resulting from a decrease in ATP, a 34% decrease in liver catalase activity, and a 20% decrease in liver vitamin C. It was interesting that glutathione increased and vitamin E remained unchanged. We found that endotoxin injury combined with burn injury produced a 61% mortality rate with a 63% decrease in liver energy charge potential, again resulting from a decrease in ATP, a 74% decrease in liver catalase activity, a 16% decrease in vitamin C, and a 29% decrease in vitamin E. Glutathione was significantly decreased compared with burn alone. We compared the liver antioxidant status of survivors with that of nonsurvivors who were killed when appearing moribund and found that glutathione was decreased by 51% and vitamin C by 73% in nonsurvivors over that in survivors, whereas catalase and vitamin E levels were comparable between the two groups. The oral administration of the antioxidants prevented mortality and the decrease in antioxidant activity and attenuated the decrease in energy charge potential. We conclude that a 20% burn produces a modest decrease in liver energy charge potential and antioxidant defenses without producing mortality. The addition of endotoxin further decreases liver antioxidant defenses, liver energy charge potential, and markedly increases mortality. Antioxidants, given post-burn, restored antioxidant defenses, attenuated the altered cell energetics, and prevented mortality, indicating oxidants to be the cause of mortality. This data also suggests that a critical value of decreases in antioxidant defenses and ATP exists, resulting in mortality.

Use of growth hormone for postoperative respiratory failure.

BACKGROUND: The authors examined the efficacy of human growth hormone (HGH) in patients dependent on mechanical ventilation who were being weaned from the respirator. METHODS: A total of 53 patients were chosen by the primary surgical team in consultation with the critical care service to undergo HGH therapy. These patients had been receiving standard ICU support and had failed standard ventilator weaning protocols. As such, they were treated with HGH in an attempt to increase respiratory muscle strength and facilitate weaning from mechanical ventilation. RESULTS: General demographic information was recorded. Patients suffered from a high incidence of co-morbid conditions and infectious complications. The average duration of HGH therapy was 38 days, and 81% of the previously unweanable patients were eventually weaned from mechanical ventilation with an overall survival of 76%. Mortality as predicted by APACHE II Scores was significantly less than actual mortality (24% actual mortality vs. 42% predicted mortality, P < 0.05). CONCLUSIONS: This phase I study presents clinical evidence supporting the safety and efficacy of HGH in promoting respiratory independence in a selected group of surgical ICU patients. Randomized, blinded, controlled trials now seem warranted.

Essential microminerals and their response to burn injury.

Certain microminerals, named because of their minute quantities in the body, are essential components for maintaining homeostasis involving, in particular, metabolism, immune defense, and wound healing. In general, these trace elements are characterized by having multiple roles and by demonstrating deficiency syndromes that are complex and difficult to diagnosis. The response of the microminerals to injury, especially burn injury, is not well defined. The purpose of this article is to describe the known roles of the trace elements and the effect of burn injury on circulating and tissue levels. As will be noted, much less is known regarding the impact of trace elements' changes on the injury process than the role of these elements in the normal state. In addition, the amount of trace elements needed for the stress changes after injury are, for the most part, undefined.

Efficacy of subcutaneous heparin in prevention of venous thromboembolic events in trauma patients.

Trauma patients have an incidence of deep venous thrombosis (DVT) of 7% to 65%. Conflicting data exists regarding the impact of prophylactic anticoagulant therapy. The purpose of this study is to assess the efficacy of DVT prophylaxis based upon our data and a meta-analysis of the current literature. Literature review revealed five recent studies that met the following criteria: 1) Adult patients sustaining major trauma (injury severity score (ISS) > 10), 2) prospective surveillance for DVT using lower extremity duplex examinations, 3) clear documentation of method of DVT prophylaxis with particular attention to the use of anticoagulation and the corresponding incidence of DVT or pulmonary embolus (PE). Additionally, 66 trauma patients in our intensive care unit were prospectively identified and followed with duplex examinations. Patients received either anticoagulation DVT prophylaxis or pneumatic compression boots. An unpaired Student t test was used to compare the characteristics of patients with and without DVT. A Mantel-Haenszel chi-square meta-analysis was performed on the five recent studies and our own data to compare the incidence of DVT/PE in patients with and without anticoagulation. Meta-analysis of the literature included 1102 patients and demonstrated no benefit from anticoagulation for DVT prophylaxis in trauma patients (10% DVT/PE with anticoagulation versus 7 per cent DVT/PE without anticoagulation, P = 0.771). Our own population had a mean age of 38 +/- 17 years, ISS of 29 +/- 11 and a length of stay (LOS) of 34 +/- 22 days. Sixteen events occurred with 13 (20%) DVTs and three (4%) pulmonary emboli.(ABSTRACT TRUNCATED AT 250 WORDS)

Micronutrients in critical illness.

Micronutrients play a key role in many of the metabolic processes that promote survival from critical illness. For vitamins, these processes include oxidative phosphorylation, which is altered in the patient with systemic inflammation, and protection against mediators, in particular oxidants. Trace elements are essential for direct antioxidant activity as well as functioning as cofactors for a variety of antioxidant enzymes. Wound healing and immune function also depend on adequate levels of vitamins and trace elements (Table 6). Of extreme importance is the ease with which a deficiency state can develop in the critically ill because of decreased nutrient intakes and increased requirements. Daily intakes up to or exceeding many times the RDA usually are required. The enteral route is preferred, although, if not available, most of these agents can be given by the parenteral route. In that case, however, dose recommendations are less clear. Attention to micronutrients is paramount both in optimizing the nutritional management of the critically ill and in the overall management of these patients. It also is essential in promoting positive outcomes and decreasing complications.