Peter I. Ramzy

Anabolic effects of oxandrolone after severe burn

ObjectiveTo explore the hypothesis that oxandrolone may reverse muscle catabolism in cachectic, critically ill pediatric burn patients. Summary Background DataSevere burn causes exaggerated muscle protein catabolism, contributing to weakness and delayed healing. Oxandrolone is an anabolic steroid that has been used in cachectic hepatitis and AIDS patients. MethodsFourteen severely burned children were enrolled during a 5-month period in a prospective cohort analytic study. There was a prolonged delay in the arrival of these patients to the burn unit for definitive care. This neglect of skin grafting and nutritional support resulted in critically ill children with significant malnutrition. On arrival, all patients underwent excision and skin grafting and received similar clinical care. Subjects were studied 5 to 7 days after admission, and again after 1 week of oxandrolone treatment at 0.1 mg/kg by mouth twice daily or no pharmacologic treatment. Muscle protein kinetics were derived from femoral arterial and venous blood samples and vastus lateralis muscle biopsies during a stable isotope infusion. ResultsControl and oxandrolone subjects were similar in age, weight, and percentage of body surface area burned. Muscle protein net balance decreased in controls and improved in the oxandrolone group. The improvement in the oxandrolone group was associated with increased protein synthesis efficiency. Muscle protein breakdown was unchanged. ConclusionsIn burn victims, oxandrolone improves muscle protein metabolism through enhanced protein synthesis efficiency. These findings suggest the efficacy of oxandrolone in impeding muscle protein catabolism in cachectic, critically injured children.

Muscle Protein Catabolism After Severe Burn: Effects of IGF-1/IGFBP-3 Treatment

OBJECTIVE To determine the effects of recombinant human insulin-like growth factor-1 (IGF-1) complexed with its principal binding protein, IGFBP-3, on skeletal muscle metabolism in severely burned children. SUMMARY BACKGROUND DATA Severe burns are associated with a persistent hypermetabolic response characterized by hyperdynamic circulation and severe muscle catabolism and wasting. Previous studies showed that nutritional support and pharmacologic intervention with anabolic agents such as growth hormone and insulin abrogated muscle wasting and improved net protein synthesis in the severely burned. The use of these agents, however, has several adverse side effects. A new combination of IGF-1 and IGFBP-3 is now available for clinical study. METHODS Twenty-nine severely burned children were prospectively studied before and after treatment with 0.5, 1, 2, or 4 mg/kg/day IGF-1/IGFBP-3 to determine net balance of protein across the leg, muscle protein fractional synthetic rates, and glucose metabolism. Another group was studied in a similar fashion without IGF-1/IGFBP-3 treatment as time controls. RESULTS Seventeen of 29 children were catabolic before starting treatment. The infusion of 1.0 mg/kg/day IGF-1/IGFBP-3 increased serum IGF-1, which did not further increase with 2.0 and 4.0 mg/kg/day. IGF-1/IGFBP-3 treatment at 1 to 4 mg/ kg/day improved net protein balance and increased muscle protein fractional synthetic rates. This effect was more pronounced in catabolic children. IGF-1/IGFBP-3 did not affect glucose uptake across the leg or change substrate utilization. CONCLUSIONS IGF-1/IGFBP-3 at doses of 1 to 4 mg/kg/day attenuates catabolism in catabolic burned children with negligible clinical side effects.

Biobrane versus 1% silver sulfadiazine in second-degree pediatric burns.

Partial‐thickness burns in children have been treated for many years by daily, painful tubbing, washing, and cleansing of the burn wound, followed by topical application of antimicrobial creams. Pain and impaired wound healing are the main problems. We hypothesized that the treatment of second‐degree burns with Biobrane is superior to topical treatment. Twenty pediatric patients were prospectively randomized in two groups to compare the efficacy of Biobrane versus 1% silver sulfadiazine. The rest of the routine clinical protocols were followed in both groups. Demographic data, wound healing time, length of hospital stay, pain assessments and pain medication requirements, and infection were analyzed and compared. Main outcome measures included pain, pain medication requirements, wound healing time, length of hospital stay, and infection. The application of Biobrane to partial‐thickness burns proved to be superior to the topical treatment. Patients included in the biosynthetic temporary cover group presented with less pain and required less pain medication. Length of hospital stay and wound healing time were also significantly shorter in the Biobrane group. None of the patients in either group presented with wound infection or needed skin autografting. In conclusion, the treatment of partial‐thickness burns with Biobrane is superior to topical therapy with 1 % silver sulfadiazine. Pain, pain medication requirements, wound healing time, and length of hospital stay are significantly reduced. (Plast. Reconstr. Surg. 105: 62, 2000.)

β-Blockade and Growth Hormone After Burn

Objective To determine whether propranolol and growth hormone (GH) have additive effects to combat burn-induced catabolism. Background Data Both GH and propranolol have been attributed anabolic properties after severe trauma and burn. It is conceivable that the two in combination would have additive effects. Methods Fifty-six children with more than 40% TBSA burns were randomized to one of four anabolic regimens: untreated control, GH treatment, propranolol treatment, or combination GH plus propranolol therapy. Clinical treatment was identical for all groups. Resting energy expenditure was determined by indirect calorimetry and skeletal muscle protein kinetics were measured using stable amino acid isotope infusions before and after each anabolic regimen. Results There were no differences in age, sex, or burn size between groups. Tachycardia and energy expenditure were decreased during propranolol treatment (P <.05). The net balance of muscle protein synthesis and breakdown was improved during proprandol and GH plus propranolol treatment (P <.05). There was no significant benefit of GH alone. No additive effect of combination therapy was seen. Conclusions Propranolol is a strongly anabolic drug during the early, hypercatabolic period after burn. No synergistic effect between propranolol and GH was identified.

Gut epithelial apoptosis after Severe burn : Effects of gut hypoperfusion

BACKGROUND Severe cutaneous burn causes transient mesenteric vasoconstriction and altered gut mucosal integrity. We recently showed that burn also increases gut epithelial cell death by apoptosis. The goal of this study was to determine whether changes in gut perfusion after burn contribute to burn-associated gut apoptosis. STUDY DESIGN We first correlated superior mesenteric artery blood flow with measurement of gut perfusion at the tissue level by laser doppler in four nonburned rats before, during, and after arterial clamping to validate our measurements of gut perfusion. We then characterized gut perfusion sequentially over time after burn; gut perfusion was measured 3 cm from the ligament of Treitz before burn and hourly for 6 hours. A group of control rats underwent the exact same protocol without the burn to exclude effects of anesthesia and laparotomy on tissue perfusion (n = 4). We studied a third group of rats with hypoperfusion of the same duration and magnitude induced mechanically without burn (n = 7). Sections of the proximal gut from all three groups (control without burn, burn, and hypoperfusion without burn) were examined for epithelial apoptosis. RESULTS Linear regression analysis demonstrated a strong correlation between superior mesenteric artery blood flow and intestinal tissue perfusion measured by laser doppler under both low and high flow conditions (r = 0.85). Laser doppler measurements of gut perfusion after burn showed deceased gut perfusion that was maximal at 2 hours postburn (p < 0.05), and that persisted for 4 hours (p < 0.05). By 6 hours, gut perfusion returned to baseline. Apoptosis increased significantly in the burn group (2.11 +/- 0.17%) compared with control (0.52 +/- 0.2%) and the mechanically decreased perfusion group (0.51 +/- .03) (p < 0.001). CONCLUSIONS We conclude that burn-induced gut hypoperfusion is insufficient to cause burn-related increased gut epithelial apoptosis. We speculate that the signal for increased gut epithelial apoptosis is primarily related to proinflammatory mediators induced by the burn wound.

Topical nystatin powder in severe burns: a new treatment for angioinvasive fungal infections refractory to other topical and systemic agents

Angioinvasive fungal infections have a significant morbidity and mortality in the immunocompromised host. Massive burns produce a profound derangement in cellular immunity along with a loss of cutaneous barrier function. Treatment of fungal burn wound infections poses a difficult therapeutic challenge. We present a new method of treatment for angioinvasive fungal infections with nystatin powder at a concentration of 6,000,000 units/g. It proved to be efficacious in four consecutive severely burned patients affected by massive angioinvasive fungal infection. Both superficial and deep tissue infections were eradicated without any other therapeutic interventions or adverse effects on wound healing.

Current Status of Anabolic Hormone Administration in Human Burn Injury

Survival after massive burns has increased due to advances in critical care and wound closure techniques. Because of the ravages of hypermetabolism that is so prevalent in these patients, survivors are left with significant lean body mass losses that correspond to decreased strength with which to begin the rehabilitation phase. Efforts to decrease lean body mass catabolism by environmental regulation, early wound closure, and sufficient caloric provision modify the hypermetabolic response to an extent; however, further manipulations are required to optimize recovery fully. Pharmacologic intervention with hormone agonists and antagonists holds this promise. This article reviews some of the current investigations in this area and points out the future work that needs to be done to elucidate the field of anabolic hormones after severe injury.

Correlation of bronchoalveolar lavage with radiographic evidence of pneumonia in thermally injured children.

The diagnosis of pneumonia in the critically ill patient is very difficult because the usual signs and symptoms are unreliable in the intensive care setting. Bronchoalveolar lavage (BAL) is a diagnostic tool with a reported sensitivity of 70%. The purpose of this study was to determine the efficacy and specificity of BAL in severely burned pediatric patients. An analysis was performed in which BAL cultures were compared and correlated to chest radiographs. Patient characteristics, such as age, sex, burn size, depth of burn, and the presence of inhalation injury were evaluated. Over a period of 18 months, 58 thermally injured children were identified who underwent 101 BALs. The mean age was 6.5 +/- 5 years, mean TBSA was 39 +/- 27%, and inhalation injury was diagnosed in 20 patients (35%). Of 101 BALs, 48 were positive, and of the 101 chest radiographs, 20 demonstrated signs of pneumonia. Ten of those were associated with a positive BAL and 10 with a negative BAL. Thus, the positive predictive value of BAL was 21%, whereas the negative predictive value was 81%. Interestingly 80% of patients with tracheobronchitis from inhalation injury demonstrated a positive BAL. We conclude that in pediatric burn patients BAL correlates poorly with radiographic signs of pneumonia.