Bacterial adhesion inhibitor prevents infection in a rodent surgical incision model.

Surgical site infection risk continues to increase due to lack of efficacy in current standard of care drugs. New methods to treat or prevent antibiotic-resistant bacterial infections are needed. Multivalent Adhesion Molecules (MAM) are bacterial adhesins required for virulence. We developed a bacterial adhesion inhibitor using recombinant MAM fragment bound to polymer scaffold, mimicking MAM7 display on the bacterial surface. Here, we test MAM7 inhibitor efficacy to prevent Gram-positive and Gram-negative infections. Using a rodent model of surgical infection, incision sites were infected with antibiotic-resistant bioluminescent strains of Staphylococcus aureus or Pseudomonas aeruginosa. Infections were treated with MAM7 inhibitor or control suspension. Bacterial abundance was quantified for nine days post infection. Inflammatory responses and histology were characterized using fixed tissue sections. MAM7 inhibitor treatment decreased burden of S. aureus and P. aeruginosa below detection threshold. Bacterial load of groups treated with control were significantly higher than MAM7 inhibitor-treated groups. Treatment with inhibitor reduced colonization of clinically-relevant pathogens in an in vivo model of surgical infection. Use of MAM7 inhibitor to block initial adhesion of bacteria to tissue in surgical incisions may reduce infection rates, presenting a strategy to mitigate overuse of antibiotics to prevent surgical site infections.

Contributions of severe burn and disuse to bone structure and strength in rats.

Burn and disuse results in metabolic and bone changes associated with substantial and sustained bone loss. Such loss can lead to an increased fracture incidence and osteopenia. We studied the independent effects of burn and disuse on bone morphology, composition and strength, and microstructure of the bone alterations 14days after injury. Sprague-Dawley rats were randomized into four groups: Sham/Ambulatory (SA), Burn/Ambulatory (BA), Sham/Hindlimb Unloaded (SH) and Burn/Hindlimb Unloaded (BH). Burn groups received a 40% total body surface area full-thickness scald burn. Disuse by hindlimb unloading was initiated immediately following injury. Bone turnover was determined in plasma and urine. Femur biomechanical parameters were measured by three-point bending tests and bone microarchitecture was determined by micro-computed tomography (uCT). On day 14, a significant reduction in body mass was observed as a result of burn, disuse and a combination of both. In terms of bone health, disuse alone and in combination affected femur weight, length and bone mineral content. Bending failure energy, an index of femur strength, was significantly reduced in all groups and maximum bending stress was lower when burn and disuse were combined. Osteocalcin was reduced in BA compared to the other groups, indicating influence of burn. The reductions observed in femur weight, BMC, biomechanical parameters and indices of bone formation are primarily responses to the combination of burn and disuse. These results offer insight into bone degradation following severe injury and disuse.

Opposition splint for partial thumb amputation: a case study measuring disability before and after splint use.

STUDY DESIGN: Case report. INTRODUCTION: A combined burn and a partial amputation can be extremely debilitating as the thumb constitutes 40% of the entire hand when evaluating functional impairment. PURPOSE OF THE STUDY: Measure disability with and without opposition splint use after partial thumb amputation due to a burn. METHODS: Impairment and disability measures were completed at discharge from the hospital and subsequently during outpatient follow-up visits while wearing and not wearing a thumb opposition splint at 3, 6, 8, and 15 months. Comparisons between disability and impairment scores were assessed over time. RESULTS: The difference between DASH scores with and without using the splint were 25 at 3 months, 16 at 6 months, 10 at 8 months, and 12 at 15 months. CONCLUSIONS: Splint use in this case demonstrated clinically significant changes over time with minimal changes in impairment indicating enhanced function and improved patient perception of disability. LEVEL OF EVIDENCE: 4.

Combat casualty care research at the U.S. Army Institute of Surgical Research.

The Institute of Surgical Research is the U.S. Army's lead research laboratory for improving the care of combat casualties. The Institute follows a rigorous process for analyzing patterns of injury and the burden of disease to determine where research can be conducted in order to positively impact care. These analyses led the ISR to focus research on: preventing death from bleeding; developing improved pain control techniques; developing improved vital signs analysis techniques; improving the treatment of extremity injuries; preventing burn injuries on the battlefield; and improving critical care for combat casualties. This process has resulted in numerous improvements in care on the battlefield. Highlights include development, fielding, and efficiency testing of tourniquets and improved dressings for bleeding control. Significant progress has also been made in the resuscitation of combat casualties using blood products instead of crystalloid or colloid solutions. Improvements in pain control include assessments of the effect of perioperative anaesthetics on the development of post-traumatic stress disorder [PTSD]. Novelvital signs analyses have been successful in identifying promising techniques which may improve the medic's ability to accurately triage patients. Current research in extremity injuries has focused on optimizing the use of negative pressure wound therapy for contaminated wounds. Burn research has focused on improving personnel protective equipment and implementing continuous renal replacement therapy. This research program is soldier focused and addresses care from self aid and buddy aid through all echelons of care. Many of these advances have been adopted in civilian medical centres as well, benefiting not only the military trauma patient, but also the civilian trauma patient.

Postexercise protein metabolism in older and younger men following moderate-intensity aerobic exercise.

Regular aerobic exercise strongly influences muscle metabolism in elderly and young; however, the acute effects of aerobic exercise on protein metabolism are not fully understood. We investigated the effect of a single bout of moderate walking (45 min at approximately 40% of peak O2 consumption) on postexercise (POST-EX) muscle metabolism and synthesis of plasma proteins [albumin (ALB) and fibrinogen (FIB)] in untrained older (n = 6) and younger (n = 6) men. We measured muscle phenylalanine (Phe) kinetics before (REST) and POST-EX (10, 60, and 180 min) using l-[ring-2H5]phenylalanine infusion, femoral arteriovenous blood samples, and muscle biopsies. All data are presented as the difference from REST (at 10, 60, and 180 min POST-EX). Mixed muscle fractional synthesis rate (FSR) increased significantly at 10 min POST-EX in both the younger (0.0363%/h) and older men (0.0830%/h), with the younger men staying elevated through 60 min POST-EX (0.0253%/h). ALB FSR increased at 10 min POST-EX in the younger men only (2.30%/day), whereas FIB FSR was elevated in both groups through 180 min POST-EX (younger men = 4.149, older men = 4.107%/day). Muscle protein turnover was also increased, with increases in synthesis and breakdown in younger and older men. Phe rate of disappearance (synthesis) was increased in both groups at 10 min POST-EX and remained elevated through 60 min POST-EX in the older men. A bout of moderate-intensity aerobic exercise induces short-term increases in muscle and plasma protein synthesis in both younger and older men. Aging per se does not diminish the protein metabolic capacity of the elderly to respond to acute aerobic exercise.

The effect of prolonged euglycemic hyperinsulinemia on lean body mass after severe burn.

BACKGROUND: The hypermetabolic response to burn increases protein catabolism. Euglycemic hyperinsu-linemia with exogenous insulin maintains muscle protein by continued stimulation of net protein synthesis. Our aim was to determine the effect of euglycemic hyperinsulinemia over the entire hospitalization on muscle anabolism by investigating lean body mass (LBM) as the primary endpoint. METHODS: Eighteen subjects between the ages of 2 and 18 with burns of more than 40% were prospectively randomized into 2 groups, a control (n = 9) and a treatment group (n = 9). The treatment group was given continuous intravenous insulin at a rate of at least 1.5 microU/kg/min to maintain serum glucose levels between 100 to 140 mg/dL. Treatment was instituted 24 to 48 hours after arrival and continued until the patient's injury was 95% healed. All patients received continuous enteral feeding. Patients underwent body composition studies by dual-energy x-ray absorptiometry (DEXA) scan on postoperative day 6 after initial burn excision and when 95% healed. RESULTS: Nutritional intakes were not different between groups. In the control, subjects continued catabolism resulted in peripheral muscle wasting and centripetal obesity with diminished truncal LBM. The treatment group had improvement in lean body mass (P =.004) and bone mass (P =.025). The treatment group also had less peripheral muscle wasting with overall increases in upper/lower extremity LBM (P =.005). Hospital length of stay in days per percent of total body surface area burned was decreased in the insulin group (control = 1.03 +/- 0.1 vs 0.7 +/- 0.9 for insulin patients; P <.05). CONCLUSIONS: Euglycemic hyperinsulinemia throughout the hospital course mitigates muscle catabolism and preserves lean body mass.

Treatment of extensive toxic epidermal necrolysis in children.

OBJECTIVE: Toxic epidermal necrolysis (TEN) is a rare but life-threatening disease of the skin and mucous membranes. We report our experience in the treatment of pediatric TEN patients with early debridement of necrotic skin and coverage with human allograft skin. METHODS: From 1984 to 2000, 15 children (6 girls, 9 boys, 7.2 +/- 1.5 years) with a histologic diagnosis of TEN and involvement of >30% total body surface area were treated at the Shriners Hospitals for Children in Galveston. All were treated in a specialized pediatric burn intensive care unit after our standard treatment protocol, including operative debridement of sloughing skin and allografting within 24 hours of admission. Outcome parameters were mortality, length of hospital stay, wound healing, clinical complications, causative drugs, corticosteroid use, and delay in referral to a burn center. RESULTS: Taking a new medication (antibiotics, anticonvulsive drugs) was associated with all cases of TEN. Patients who were treated with early debridement and coverage with allograft skin showed no wound infection, and overall mortality was 7%. Total length of hospital stay was 26 +/- 3 days. Long-term sequelae were changes in skin pigmentation (100%), ophthalmologic problems (40%), and diffuse itching early after wound healing (53%). CONCLUSION: Although a rare disease in children, TEN was managed successfully in a burn center environment, using early debridement and wound coverage with allograft skin as a biological dressing. The use of corticosteroids and referral patterns seems unchanged during the past 2 decades, indicating an additional need for information and education about the disease.

Reversal of catabolism by beta-blockade after severe burns.

BACKGROUND: The catecholamine-mediated hypermetabolic response to severe burns causes increased energy expenditure and muscle-protein catabolism. We hypothesized that blockade of beta-adrenergic stimulation with propranolol would decrease resting energy expenditure and muscle catabolism in patients with severe burns. METHODS: Twenty-five children with acute and severe burns (more than 40 percent of total body-surface area) were studied in a randomized trial. Thirteen received oral propranolol for at least two weeks, and 12 served as untreated controls. The dose of propranolol was adjusted to decrease the resting heart rate by 20 percent from each patient's base-line value. Resting energy expenditure and skeletal-muscle protein kinetics were measured before and after two weeks of beta-blockade (or no therapy, in controls). Body composition was measured serially throughout hospitalization. RESULTS: Patients in the control group and the propranolol group were similar with respect to age, weight, percentage of total body-surface area burned, percentage of body-surface area with third-degree burns, and length of time from injury to metabolic study. Beta-blockade decreased the heart rates and resting energy expenditure in the propranolol group, both as compared with the base-line values (P<0.001 and P=0.01, respectively) and as compared with the values in the control group (P=0.03 and P=0.001, respectively). The net muscle-protein balance increased by 82 percent over base-line values in the propranolol group (P=0.002), whereas it decreased by 27 percent in the control group (P not significant). The fat-free mass, as measured by whole-body potassium scanning, did not change substantially in the propranolol group, whereas it decreased by a mean (+/-SE) of 9+/-2 percent in the control group (P=0.003). CONCLUSIONS: In children with burns, treatment with propranolol during hospitalization attenuates hypermetabolism and reverses muscle-protein catabolism.

Testosterone administration in severe burns ameliorates muscle catabolism.

OBJECTIVE: To assess the effects of testosterone administration on muscle protein metabolism after severe burn injury. We hypothesized that restoration of blood testosterone concentrations would restore an important anabolic stimulus to skeletal muscle, and would further increase the anabolic response of muscle to amino acid supplementation. DESIGN: Pre- and postintervention trial conducted between September 1997 and July 1999. SETTING: Burn intensive care unit. PATIENTS: Six severely burned male patients (>70% total body surface area). INTERVENTION: Testosterone enanthate, 200 mg/wk (intramuscularly), for 2 wks. MEASUREMENTS AND MAIN RESULTS: Muscle protein synthesis, breakdown, and amino acid kinetics were determined. After a basal period in each study, we subsequently investigated the response to acute amino acid supplementation during enteral feeding. Total testosterone increased significantly from baseline to the low normal range after 1 wk, and to upper normal range after two injections (p <.001). Protein synthesis was unchanged, however, protein synthetic efficiency increased 2-fold (p <.01). Protein breakdown decreased almost 2-fold after testosterone enanthate (p <.05), resulting in an improvement in net amino acid balance to a value that was approximately zero (p <.0001). Amino acid supplementation at either time point provided no additional effects. CONCLUSIONS: Restoration of blood testosterone can ameliorate the muscle catabolism of severe burn injury with normal feedings.

Association of hyperglycemia with increased mortality after severe burn injury.

BACKGROUND: Hyperglycemia is commonly associated with the hypermetabolic stress response. However, persistent hyperglycemia may adversely affect wound healing and immunity. The purpose of this study was to assess any relationship between hyperglycemia and clinical outcome after severe burn injury. METHODS: Survey of the medical records from January 1996 to July 1999 identified 58 pediatric patients with burns > or = 60% body surface. Patients were categorized as having poor glucose control (n = 33) if > or = 40% of all plasma glucose determinations were > or = 7.8 mmol/L (140 mg/dL) and compared with patients deemed to have adequate glucose control (n = 25) in whom > or = 40% of all glucose values were > or = 7.8 mmol/L. RESULTS: Despite similar age, burn size, caloric intake, and frequency of wound infection, patients categorized with poor glucose control had a significantly greater incidence of positive blood cultures (positive blood cultures/length of stay days, 0.42 +/- 0.04 for hyperglycemia patients vs. 0.30 +/- 0.03 for normoglycemia patients; mean +/- SEM, p > or = 0.05). This finding was especially prominent for blood cultures positive for yeast. Hyperglycemia patients had significantly less percentage of skin graft take than did the normoglycemic patients (percent take/operative procedure, 64 +/- 9 for hyperglycemia patients vs. 88 +/- 5 for normoglycemia patients; p < 0.05). Nine patients (27%) with persistent hyperglycemia died compared with only one death (4%) in patients with adequate glucose control (p > or = 0.05). CONCLUSION: This association between poor glucose control, bacteremia/fungemia, reduced skin graft take, and subsequent mortality in severely burned children may be related to a hyperglycemia-induced detriment in antimicrobial defense. Although this report fails to establish cause and effect, these findings suggest that aggressive maneuvers to normalize plasma glucose in critically injured patients may be warranted.

Determinants of blood loss during primary burn excision.

BACKGROUND: Excisional therapy for burn wounds is frequently associated with large operative blood losses. Our objective was to identify patient and operative factors that affect surgical blood loss and determine strategies to minimize hemorrhage. METHODS: Data from 92 consecutive pediatric patients with severe burns (>40% total body surface area) were evaluated. Patient demographics, burn characteristics, operative factors, and clinical course variables were correlated with blood loss. Blood loss at the time of initial total burn excision was determined by a standardized, previously validated method. Data were analyzed sequentially and cumulatively through univariate and cross-sectional multivariate linear regression. RESULTS: Demographic factors that correlated with increased blood loss were older age, male sex, and larger body size. Area of full-thickness (third-degree) burn correlated with blood loss, whereas total burn size did not. High wound bacteria counts (derived from quantitative tissue cultures), total wound area excised, and operative time were the strongest predictors of the volume of operative hemorrhage. Blood loss increased with delay to primary burn excision at a maximum at 5 to 12 days after burn injury. CONCLUSIONS: Early definitive surgical therapy before extensive bacterial colonization and rapid operative excision is a strategy that may decrease operative hemorrhage and transfusion requirements during burn surgical procedures.

Efficacy of a high-carbohydrate diet in catabolic illness.

OBJECTIVE: To determine within the setting of isocaloric, isonitrogenous enteral diets whether a diet that supplies most of its calories from fat or carbohydrate would be most beneficial at limiting muscle protein wasting in catabolic illness. DESIGN: Prospective, randomized, crossover trial. SETTING: Academic pediatric burn unit in tertiary medical center. PATIENTS: Fourteen severely burned (>40% total body surface area) children underwent systemic metabolic and cross-leg muscle protein kinetic studies. INTERVENTIONS: All were treated clinically in a similar manner, including early excision and grafting, antimicrobial therapy, and isocaloric, isonitrogenous enteral nutritional support. Subjects randomly received either a high-carbohydrate enteral diet (3% fat, 82% carbohydrate, 15% protein), or a high-fat enteral diet (44% fat, 42% carbohydrates, 14% protein) for 1 week and then crossed over to the other diet for a second week. MEASUREMENTS AND MAIN RESULTS: On day 5 of each diet, muscle protein kinetics were determined from femoral arterial and venous blood samples during a primed-constant d5-phenylalanine infusion. Indirect calorimetry was used to determine systemic resting energy expenditure and respiratory quotient. The seven boys and seven girls were 7.1 +/- 1.1 (mean +/- sem) years old and suffered burns over 65 +/- 4% of their bodies, with 52 +/- 6% being third-degree burns. Muscle protein degradation markedly decreased (p <.01) with administration of the high-carbohydrate diet. Protein synthesis was unaltered. Endogenous insulin concentrations increased during the high-carbohydrate feeding period. No differences in energy expenditure were seen between study diets. CONCLUSIONS: In severely burned pediatric patients, enteral nutrition supplied predominantly as carbohydrate rather than fat improves the net balance of skeletal muscle protein across the leg. This is attributable to decreased protein breakdown, suggesting a protein-sparing effect of high-carbohydrate feedings.

Timing of amino acid-carbohydrate ingestion alters anabolic response of muscle to resistance exercise.

The present study was designed to determine whether consumption of an oral essential amino acid-carbohydrate supplement (EAC) before exercise results in a greater anabolic response than supplementation after resistance exercise. Six healthy human subjects participated in two trials in random order, PRE (EAC consumed immediately before exercise), and POST (EAC consumed immediately after exercise). A primed, continuous infusion of L-[ring-(2)H(5)]phenylalanine, femoral arteriovenous catheterization, and muscle biopsies from the vastus lateralis were used to determine phenylalanine concentrations, enrichments, and net uptake across the leg. Blood and muscle phenylalanine concentrations were increased by approximately 130% after drink consumption in both trials. Amino acid delivery to the leg was increased during exercise and remained elevated for the 2 h after exercise in both trials. Delivery of amino acids (amino acid concentration times blood flow) was significantly greater in PRE than in POST during the exercise bout and in the 1st h after exercise (P < 0.05). Total net phenylalanine uptake across the leg was greater (P = 0.0002) during PRE (209 +/- 42 mg) than during POST (81 +/- 19). Phenylalanine disappearance rate, an indicator of muscle protein synthesis from blood amino acids, increased after EAC consumption in both trials. These results indicate that the response of net muscle protein synthesis to consumption of an EAC solution immediately before resistance exercise is greater than that when the solution is consumed after exercise, primarily because of an increase in muscle protein synthesis as a result of increased delivery of amino acids to the leg.

Attenuation of posttraumatic muscle catabolism and osteopenia by long-term growth hormone therapy.

OBJECTIVE: To determine whether the beneficial effects of growth hormone persist throughout the prolonged hypermetabolic and hypercatabolic response to severe burn. SUMMARY BACKGROUND DATA: The hypermetabolic response to severe burn is associated with increased energy expenditure, insulin resistance, immunodeficiency, and whole body catabolism that persists for months after injury. Growth hormone is a potent anabolic agent and salutary modulator of posttraumatic metabolic responses. METHODS: Seventy-two severely burned children were enrolled in a placebo-controlled double-blind trial investigating the effects of growth hormone (0.05 mg/kg per day) on muscle accretion and bone growth. Drug or placebo treatment began on discharge from the intensive care unit and continued for 1 year after burn. Total body weight, height, dual-energy x-ray absorptiometry, indirect calorimetry, and hormone values were measured at discharge, then at 6 months, 9 months, and 12 months after burn. Results were compared between groups. RESULTS: Growth hormone subjects gained more weight than placebo subjects at the 9-month study point; this disparity in weight gain continued to expand throughout the remainder of the study. Height also increased in the growth hormone group compared with controls at 12 months. Change in lean body mass was greater in those treated with growth hormone at 6, 9, and 12 months. Bone mineral content was increased at 9 and 12 months; this was associated with higher parathormone levels. CONCLUSIONS: Low-dose recombinant human growth hormone successfully abates muscle catabolism and osteopenia induced by severe burn.

Anabolic effects of oxandrolone after severe burn.

OBJECTIVE: To explore the hypothesis that oxandrolone may reverse muscle catabolism in cachectic, critically ill pediatric burn patients. SUMMARY BACKGROUND DATA: Severe 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. METHODS: Fourteen 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. RESULTS: Control 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. CONCLUSIONS: In 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.

Influence of glucose kinetics on plasma lactate concentration and energy expenditure in severely burned patients.

BACKGROUND: In critically ill patients, elevation in the plasma lactate concentration has traditionally been interpreted as indicating a deficiency in oxygen availability and is often an impetus to increase oxygen delivery clinically. However, another possible basis for increased lactate concentrations may be simply a mass effect from increased pyruvate availability (i.e., accelerated glycolysis). METHODS: In six hypermetabolic burned patients, the rates of glucose production and oxidation were quantified using a tracer infusion of 6,6 d2 glucose combined with indirect calorimetry. Measurements were obtained after a 9-hour fast and after a 3-hour infusion of unlabeled glucose at 30 micromol/kg/min. No patient was overtly septic, hypoxic, or hypovolemic. RESULTS: The infusion of glucose significantly increased the arterial glucose concentration and rate of glucose oxidation, with a corresponding increase in the arterial plasma concentration of lactate and pyruvate. Resting energy expenditure and oxygen consumption were not affected by the infusion of glucose. CONCLUSIONS: These findings show that elevations in plasma lactate in severely injured patients may, in part, be related to increases in glucose flux and not entirely a reflection of any deficit in oxygen availability. Such findings highlight a potential pitfall for interpreting plasma lactate concentrations as an index of tissue oxygen availability in hypermetabolic patients.

Biobrane improves wound healing in burned children without increased risk of infection.

A synthetic bilaminar membrane used as a skin substitute (Biobrane) has been shown to decrease pain and hospitalization in superficial second-degree burns. Despite these benefits, it has not been utilized universally, particularly in young children, due to a perceived increase in related infections. We propose that when this synthetic membrane is applied to superficial scald burns <25% of the total body surface area (TBSA), decreased healing times are expected without increased risk of infection. Between 1994-1999, 89 children treated within 48 h after receiving superficial partial thickness scald burns covering 5-25% TBSA with no indication of infection were seen at our hospital. Forty-one were assigned randomly to receive treatment with the skin substitute Biobrane and 48 to receive conservative treatment with topical antimicrobials and dressing changes. Comparisons of treatment were made between groups for length of hospitalization, wound healing times, and infectious complications. Children treated with Biobrane or topical antimicrobials were similar in age, race, sex, %TBSA burned, and location of burn. Those receiving Biobrane had shorter hospitalizations and healing times, which was significant for both infants and toddlers and older children. Treatment groups were not different in the use of systemic antibiotics or readmissions for infectious complications. Biobrane was removed in 5.9% of cases for non-adherence. The application of Biobrane within 48 h of superficial burns provides for shorter hospitalizations and faster healing times in children of all ages without increased risk of infection.

Determinants of skeletal muscle catabolism after severe burn.

OBJECTIVE: To determine which patient factors affect the degree of catabolism after severe burn. SUMMARY BACKGROUND DATA: Catabolism is associated with severe burn and leads to erosion of lean mass, impaired wound healing, and delayed rehabilitation. METHODS: From 1996 to 1999, 151 stable-isotope protein kinetic studies were performed in 102 pediatric and 21 adult subjects burned over 20-99. 5% of their total body surface area (TBSA). Patient demographics, burn characteristics, and hospital course variables were correlated with the net balance of skeletal muscle protein synthesis and breakdown across the leg. Data were analyzed sequentially and cumulatively through univariate and cross-sectional multiple regression. RESULTS: Increasing age, weight, and delay in definitive surgical treatment predict increased catabolism (P < .05). Body surface area burned increased catabolism until 40% TBSA was reached; catabolism did not consistently increase thereafter. Resting energy expenditure and sepsis were also strong predictors of net protein catabolism. Among factors that did not significantly correlate were burn type, pneumonia, wound contamination, and time after burn. From these results, the authors also infer that gross muscle mass correlates independently with protein wasting after burn. CONCLUSIONS: Heavier, more muscular subjects, and subjects whose definitive surgical treatment is delayed are at the greatest risk for excess catabolism after burn. Sepsis and excessive hypermetabolism are also associated with protein catabolism.

Differential expression of hepatocyte growth factor in liver, kidney, lung, and spleen following burn in rats.

Hepatocyte growth factor (HGF) plays a role as an organotropic factor for regeneration of injured organs. HGF is synthesized as an inactive single-chain precursor which is then converted to a biologically active heterodimeric form by proteolytic processing. Burn is the insult that results in hypovolemia which causes systemic organ injury. In this study, we investigated the induction and activation of HGF in various rat organs following burn trauma. Tissue HGF content determined as the total amount of the single-chain and heterodimeric form increased significantly in liver, lung, spleen, and kidney 12 h after burn. Molecular analysis revealed that HGF in these four organs of control rats was the single-chain precursor. In the burned rats, HGF was the single-chain form in the liver and lung, whereas heterodimeric HGF was detected in the spleen and kidney. Tissue protein content, an index of tissue injury, decreased significantly in the spleen and kidney, indicating that tissue damage was severe in these two organs. These results suggest that burn induces the production of HGF in various organs, and that the induced HGF is activated according to the severity of tissue damage caused by burn.

Growth hormone, burns and tissue healing.

Severe illness or trauma alters the body's metabolic rate. After injury, host-defence protein synthesis and increased energy requirements are satisfied from available protein, usually active muscle tissue. A prolonged hypercatabolic state persists and may lead to increased morbidity and mortality in severely burned patients. Growth hormone (GH) is an anabolic agent shown to decrease some of the deleterious effects of hypermetabolism. This article will review the effects of GH on burn wound repair and gut healing. Studies on GH have shown a significant reduction in wound-healing times in burned patients given GH at a dose of 0.6 IU/kg/day (0.2 mg/kg/day). At this dose, other studies have shown no increase in mortality, and a number of beneficial effects in critically burned children have been demonstrated. Animal studies have suggested that insulin-like growth factor I (IGF-I), stimulated through the GH axis, plays an important role in the reconstitution of intestinal epithelial integrity following mucosal injury. Many encouraging papers report positive results regarding both the efficacy and safety of GH and IGF-I, therefore warranting continued investigation.