Amino Acid Availability Regulates the Effect of Hyperinsulinemia on Skin Protein Metabolism in Pigs.

The effects of amino acid supply and insulin infusion on skin protein kinetics (fractional synthesis rate (FSR), fractional breakdown rate (FBR), and net balance (NB)) in pigs were investigated. Four-month-old pigs were divided into four groups as follows: control, insulin (INS), amino acid (AA), and INS + AA groups based on the nutritional and hormonal conditions. l-[ring-(13)C6]Phenylalanine was infused. FBR was estimated from the enrichment ratio of arterial phenylalanine to intracellular free phenylalanine. Plasma INS was increased (p < 0.05) in the INS and INS + AA groups. Plasma glucose was maintained by infusion of glucose in the groups receiving INS. The interventions did not change the NB of skin protein. However, the interventions affected the FSR and FBR differently. An infusion of INS significantly increased both FSR and FBR, although AA infusion did not. When an AA infusion was added to the infusion of insulin (INS + AA group), FSR and FBR were both lower when compared with the INS group. Our data demonstrate that in anesthetized pigs INS infusion did not exert an anabolic effect, but rather it increased AA cycling into and out of skin protein. Because co-infusion of AAs with INS ameliorated this effect, it is likely that the increased AA cycling during INS infusion was related to AA supply. Although protein kinetics were affected by both INS and AAs, none of the interventions affected the skin protein deposition. Thus, skin protein content is closely regulated under normal circumstances and is not subject to transient changes in AAs or hormonal concentrations.

Triglycerides produced in the livers of fasting rabbits are predominantly stored as opposed to secreted into the plasma.

OBJECTIVE: The liver plays a central role in regulating fat metabolism; however, it is not clear how the liver distributes the synthesized triglycerides (TGs) to storage and to the plasma. MATERIALS AND METHODS: We have measured the relative distribution of TGs produced in the liver to storage and the plasma by means of U-(13)C(16)-palmitate infusion in anesthetized rabbits after an overnight fast. RESULTS: The fractional synthesis rates of TGs stored in the liver and secreted into the plasma were not significantly different (stored vs. secreted: 31.9 ± 0.8 vs. 27.7 ± 2.6%∙h(-1), p > 0.05). However, the absolute synthesis rates of hepatic stored and secreted TGs were 543 ± 158 and 27 ± 7 nmol∙kg(-1)∙min(-1) respectively, indicating that in fasting rabbits the TGs produced in the liver were predominately stored (92 ± 3%) rather than secreted (8 ± 3%) into the plasma. This large difference was mainly due to the larger pool size of the hepatic TGs which was 21 ± 9-fold that of plasma TGs. Plasma free fatty acids (FFAs) contributed 47 ± 1% of the FA precursor for hepatic TG synthesis, and the remaining 53 ± 1% was derived from hepatic lipid breakdown and possibly plasma TGs depending on the activity of hepatic lipase. Plasma palmitate concentration significantly correlated with hepatic palmitoyl-CoA and TG synthesis. CONCLUSION: In rabbits, after an overnight fast, the absolute synthesis rate of hepatic stored TGs was significantly higher than that of secreted due to the larger pool size of hepatic TGs. The net synthesis rate of TG was approximately half the absolute rate. Plasma FFA is a major determinant of hepatic TG synthesis, and therefore hepatic TG storage.

Comparison of bolus injection and constant infusion methods for measuring muscle protein fractional synthesis rate in humans.

BACKGROUND: The use of stable isotope tracer techniques to measure muscle protein fractional synthesis rate (FSR) has been well established and widely used. The most common method that has been utilized so far is a primed constant infusion (CI) method, which requires 3-4 h of tracer infusion. However, recently our group has developed a bolus injection (BI) method, which requires an injection of bolus of tracer and can be completed within 1 h. In this study, we compared calf (gastrocnemius) muscle protein FSR measured using these two different methods--CI and BI. METHOD: FSRs were measured in eight people (5 men and 3 women; age: 62.3±6.9 years (mean±SD); body weight: 75.4±21.5 kg) at basal, postabsorptive state using L-[ring-2H5]-phenylalanine. In the CI protocol, a primed continuous infusion was given for 4 h, and muscle biopsies were taken at 120 and 240 min; in the BI, a bolus injection of the tracer was given at 0 min and biopsies were taken at 5 and 60 min. Tracer enrichments in blood and muscle tissue were determined by gas chromatography-mass spectrometry. Data are expressed as mean±SE; t-test, linear regression and Levene Median equal variance test analyses were performed. RESULTS: CI FSR was 0.066±0.006%/h, whereas BI FSR was 0.058±0.008%/h, p=NS. The linear regression analysis showed a significant relationship between BI and CI, p=0.038. The intra-class correlation coefficient was 0.83. The standard deviation of the differences in the measurements was 0.015%/h. The Levene Median equal variance test demonstrated no difference in variance between the CI and BI measurements (p=0.722). CONCLUSION: No difference could be detected in calf muscle protein FSR measured by CI and BI methods; the BI method can be used for the measurement of muscle protein FSR in humans.

A novel stable isotope tracer method to measure muscle protein fractional breakdown rate during a physiological non-steady-state condition.

The measurement of the fractional breakdown rate (FBR) of muscle proteins during physiological non-steady state of amino acids (AAs) presents some challenges. Therefore, the goal of the present experiment was to modify the bolus stable isotope tracer injection approach to determine both fractional synthesis rate (FSR) and FBR of leg muscle protein during a physiological non-steady state of AAs. The approach uses the traditional precursor-product principle but is modified with the assumption that inward transport of AAs is proportional to their plasma concentrations. The FBR value calculated from the threonine tracer served as a reference to evaluate the validity of the FBR measurement from the phenylalanine tracer, which was under a non-steady-state condition due to the concomitant injection of unlabeled phenylalanine. Plasma phenylalanine concentration increased more than fourfold after the bolus injection, and thereafter it decreased exponentially, whereas the threonine concentration remained stable. FBR values were similar with the two tracers [0.133 ± 0.003 and 0.148 ± 0.003%/h (means ± SE) for the phenylalanine and threonine tracers, respectively, P > 0.05]. In addition, FSR values for the two tracers were similar (0.069 ± 0.002 and 0.067 ± 0.001%/h for the phenylalanine and threonine tracers, respectively, P > 0.05), indicating that the traditional FSR approach can also be used in the non-steady state. Accordingly, net balance (NB) values were similar (-0.065 ± 0.002 and -0.081 ± 0.002%/h for the phenylalanine and threonine tracers, respectively, P > 0.05). This new method of measuring muscle protein FBR during physiological non-steady state gives reliable results and allows simultaneous measurement of muscle protein FSR and thus a calculation of NB.

Adult patients are more catabolic than children during acute phase after burn injury: a retrospective analysis on muscle protein kinetics.

PURPOSE: This study was performed to determine if there is an age-related specificity in the response of muscle protein metabolism to severe burn injury during acute hospitalization. This is a retrospective analysis of previously published data. METHODS: Nineteen adult and 58 pediatric burn-injured patients (age 43.3 ± 14.3 vs. 7.2 ± 5.3 years, adult vs. children) participated in stable isotope [ring-(2)H(5)]phenylalanine (Phe) infusion studies. Femoral arterial and venous blood samples and muscle biopsy samples were collected throughout the study. Data are presented as means ± standard deviation (SD). A p value less than 0.05 was considered statistically significant. RESULTS: Muscle net protein balance (NB) was higher in children (adult vs. children, -43 ± 61 vs. 8 ± 68 nmol Phe/min/100 ml leg volume, p < 0.05). Muscle protein fractional synthesis rate (FSR) was higher in children (adult vs. children, 0.11 ± 0.05 vs. 0.16 ± 0.10 %/h, p < 0.05). Leg muscle protein breakdown was not different between the groups (adult vs. children, 179 ± 115 vs. 184 ± 124 nmol Phe/min/100 ml leg volume, p > 0.05); synthesis rate was 134 ± 96 and 192 ± 128 nmol Phe/min/100 ml leg volume in adults and children, respectively (p = 0.07). Age significantly correlated with muscle protein NB (p = 0.01) and FSR (p = 0.02); but not with breakdown (p = 0.67) and synthesis (p = 0.07) rates measured by using a three-pool model. CONCLUSION: In burn injury, the muscle protein breakdown may be affected to the same extent in adults and children, whereas synthesis may have age-related specificities, resulting in a better but still low NB in children.

Enternal [corrected] arginine supplementation stimulates DNA synthesis in skin donor wound.

BACKGROUND & AIMS: Arginine infusion has been demonstrated to increase wound protein deposition; however, the effects of its enteral supplementation on wound cell proliferation have not been studied. METHODS: Skin donor wound was created on the back of rabbits. The rabbits were randomly assigned to receive a control enteral diet, or the control enteral diet with supplemental arginine. On day 5 L-[ring-(13)C(6)]phenylalanine and D-[U-(13)C(6)]glucose were infused to measure the fractional synthetic rates of DNA (reflecting cell proliferation) and protein in the wound. RESULTS: In the arginine group (n = 6) plasma arginine concentration was increased to 2.8 fold that in the control group (n = 8), which was a less increase than that of 6.4 fold for ornithine. Wound DNA fractional synthetic rate was 5.37 ± 0.21%/day in the arginine group, greater (p < 0.05) than that of 4.27 ± 0.35%/day in the control group. Protein fractional synthetic rates in the wound were comparable between the two groups. CONCLUSIONS: Enternal arginine supplementation increased wound DNA synthesis, which is anticipated to promote cell proliferation for wound healing. The failure of enteral arginine to stimulate protein synthesis is explained by limited increase in plasma arginine. Decreased availability of essential amino acids, especially branched chain amino acids, may also contribute to the failure to stimulate protein synthesis.

Long-term oxandrolone treatment increases muscle protein net deposition via improving amino acid utilization in pediatric patients 6 months after burn injury.

BACKGROUND: We recently showed that mechanisms of protein turnover in skeletal muscle are unresponsive to amino acid (AA) infusion in severely burned pediatric patients at 6 months postinjury. In the current study, we evaluated whether oxandrolone treatment affects mechanisms of protein turnover in skeletal muscle and whole-body protein breakdown in pediatric burn patients 6 months postinjury. METHODS: At the time of admission, patients were randomized to control or oxandrolone treatments. The treatment regimens were continued until 6 months postinjury, at which time patients (n = 26) underwent study with a stable isotope tracer infusion to measure muscle and whole-body protein turnover. RESULTS: Protein kinetics in leg muscle were expressed in nmol/min per 100 mL leg volume (mean ± SE). During AA infusion, rates of protein synthesis in leg muscle were increased (P < .05) in both groups (basal vs AA: control, 51 ± 8 vs 86 ± 21; oxandrolone, 56 ± 7 vs 96 ± 12). In the control group, there was also a simultaneous increase in breakdown (basal vs AA: 65 ± 10 vs 89 ± 25), which resulted in no change in the net balance of leg muscle protein (basal vs AA: -15 ± 4 vs -2 ± 10). In the oxandrolone group, protein breakdown did not change (basal vs AA: 80 ± 12 vs 77 ± 9), leading to increased net balance (basal vs AA: -24 ± 7 vs 19 ± 7; P < .05). Protein breakdown at the whole-body level was not different between the groups. CONCLUSION: Long-term oxandrolone treatment increased net deposition of leg muscle protein during AA infusion by attenuating protein breakdown, but did not affect whole-body protein breakdown.

Skeletal muscle is anabolically unresponsive to an amino acid infusion in pediatric burn patients 6 months postinjury.

OBJECTIVE: To evaluate leg muscle, whole-body muscle, and whole-body nonmuscle protein response to anabolic signaling of amino acids in pediatric burn patients at 6 months after injury. BACKGROUND: Burn injury is associated with a catabolic state persisting years after the injury. The tissue response to nutritional signaling (eg, amino acids) plays a critical role in tissue protein net balance via coordination of protein synthesis and breakdown mechanisms. METHODS: A total of 10 patients (7.4 ± 3.8 years; 27.4 ± 14.7 kg) and 5 healthy young males (22 ± 3 years; 76 ± 15 kg) underwent an 8-hour stable isotope infusion study. During the last 3 hours, an amino acid solution (10% Travasol, Clintec Nutrition, Deerfield, IL) was infused. Femoral arterial and venous blood samples and muscle biopsy samples were collected throughout the study. A P value of less than 0.05 was considered statistically different. RESULTS: During amino acid infusion, leg muscle protein synthesis rate significantly increased (P < 0.05) in both groups, however, in the burn group, protein breakdown also increased, although nonsignificantly. As a result, protein net balance remained negative. In the control group, breakdown nonsignificantly decreased resulting in a significant increase (P < 0.05) in muscle protein net balance. Whole-body protein breakdown was significantly higher in the burn patients. CONCLUSION: In pediatric burn patients at 6 months postinjury, leg muscle protein net deposition is unresponsive to amino acid infusion; and whole-body protein breakdown is significantly higher than in the control group.

Intensive insulin treatment increases donor site wound protein synthesis in burn patients.

BACKGROUND: In the treatment of burns, patients' own skin is the preferred material to cover burn wounds, resulting in the need to create a donor site wound. Enhancement of healing of the donor site wound would be beneficial in burn patients. Insulin, an anabolic agent, is used routinely to treat hyperglycemia after injury. We investigated whether intensive insulin treatment increases fractional synthesis rate (FSR) of the donor site wound protein and decreases the length of hospitalization normalized for total body surface area burned (LOS/TBSA). METHODS: FSR of the donor site wound protein was measured in pediatric patients randomized to control (n = 13) and insulin (n = 10) treatments. Depending on the postoperative day when the tracer study was done, studies were divided into "early" (days < 5) and "late" (days ≥ 5) periods. RESULTS: FSR of the donor site wound protein was greater in the insulin group at the "early" period of wound healing (control vs insulin, 8.2 ± 3.8 vs 13.1 ± 6.9% per day; P < .05); but not at the "late" (control vs insulin, 19.7 ± 4.6 vs 16.6 ± 4.0% per day; P > .05). Despite these differences, LOS/TBSA was not decreased in the insulin group. Correlation analyses demonstrated that, independent of the treatment regimen, FSR positively correlated (P < .05) with time after creation of the donor site and negatively correlated (P < .05) with LOS/TBSA. CONCLUSION: Insulin treatment increased FSR of the donor site wound protein in the early period of wound healing; FSR correlated with LOS/TBSA independent of the treatment regimen.

Beneficial effects of insulin on cell proliferation and protein metabolism in skin donor site wound.

BACKGROUND: Insulin has been demonstrated to accelerate skin wound healing; however, its effects on wound metabolism have not been adequately studied. MATERIALS AND METHODS: Adult rabbits were prepared by creation of skin donor site wound on the back, catheterization of the carotid artery and jugular vein, and placement of a nasogastric feeding tube under general anesthesia. The rabbits were given total enteral nutrition thereafter. On day 5 stable isotope tracers were infused to measure the kinetics of protein (reflecting tissue repair) and DNA (reflecting cell proliferation) in the wound. During the isotope tracer infusion, regular human insulin was infused at 2.5 mU/kg per min with concomitant glucose infusion for euglycemia in an insulin group but not in a control group. RESULTS: Plasma insulin concentration was 140±26 µU/mL in the insulin group (n=8), greater (P<0.001) than that of 16±3 µU/mL in the control group (N=8). In the insulin group the fractional synthetic rates of wound protein and DNA were 9.0±1.2 and 5.4±0.5%/day, greater (P < or=0.05) than those of 6.4±0.5 and 4.0±0.6%/day in the control group, respectively. Wound protein fractional breakdown rates were not significantly (P =0.2) different; net protein deposition rate was ~50% greater in the insulin than in the control group, although the difference was not statistically different (P=0.2). CONCLUSIONS: Insulin infusion increased wound protein and DNA synthesis, which are anticipated to promote tissue repair and reepithelialization.

Temperature responses in severely burned children during exercise in a hot environment.

The authors have previously described thermoregulatory responses of severely burned children during submaximal exercise in a thermoneutral environment. However, the thermoregulatory response of burned children to exercise in the heat is not well understood and could have important safety implications for rehabilitation. Children (n = 10) with >40% TBSA burns and nonburned children (n = 10) performed a 30-minute bout of treadmill exercise at 75% of their peak aerobic power in a heated environment. Intestinal temperature, burned and unburned skin temperature, and heart rate were recorded pre-exercise, every 2 minutes during exercise, and during recovery. Three of the 10 burned children completed the exercise bout in the heat; however, all the nonburned children completed the 30-minute bout. One burned child reached a core body temperature >39 degrees C at minute 23. Burned children had significantly higher core body temperature through the first 12 minutes of exercise compared with nonburned children. However, nine of 10 (90%) burned children did not become hyperthermic during exercise in the heat. Specific to this study, hyperthermia did not typically occur in burned children, relative to nonburned children. Whether this is due to an intolerance to exercise in the heat or to an inability to generate sufficient heat during exercise needs to be explored further.

Whole body protein kinetics measured with a non-invasive method in severely burned children.

UNLABELLED: Persistent and extensive skeletal muscle catabolism is characteristic of severe burns. Whole body protein metabolism, an important component of this process, has not been measured in burned children during the long-term convalescent period. The aim of this study was to measure whole body protein turnover in burned children at discharge (95% healed) and in healthy controls by a non-invasive stable isotope method. Nine burned children (7 boys, 2 girls; 54±14 (S.D.)% total body area burned; 13±4 years; 45±20 kg; 154±14 cm) and 12 healthy children (8 boys, 4 girls; 12±3 years; 54±16 kg; 150±22 cm) were studied. A single oral dose of (15)N-alanine (16 mg/kg) was given, and thereafter urine was collected for 34 h. Whole body protein flux was calculated from labeling of urinary urea nitrogen. Then, protein synthesis was calculated as protein flux minus excretion, and protein breakdown as flux minus intake. At discharge, total protein turnover was 4.53±0.65 (S.E.)g kg body weight(-1) day(-1) in the burned children compared to 3.20±0.22 g kg(-1) day(-1) in controls (P=0.02). Expressed relative to lean body mass (LBM), the rates were 6.12±0.94 vs. 4.60±0.36 g kg LBM(-1) day(-1) in burn vs. healthy (P=0.06). Total protein synthesis was also elevated in burned vs. healthy children, and a tendency for elevated protein breakdown was observed. CONCLUSION: Total protein turnover is elevated in burned children at discharge compared to age-matched controls, possibly reflecting the continued stress response to severe burn. The oral (15)N-alanine bolus method is a convenient, non-invasive, and no-risk method for measurement of total body protein turnover.

Donor site wound protein synthesis correlates with length of acute hospitalization in severely burned children.

Autografting of burn wounds results in generation of donor site wounds. Here we measured donor site wound protein fractional synthesis rate (FSR) in a burn pediatric population and showed that FSR increases over time postsurgery and correlates with the length of hospital stay (LOS) normalized for total body surface area (TBSA) burn size. 3.9 +/- 1.1 days after the grafting surgery patients participated in a metabolic study consisting of continuous infusion of l-[ring-(2)H(5)]-phenylalanine and donor site wound punch biopsies. Donor site wound protein FSR was 10.4 +/- 7.5%/day. Wound FSR demonstrated linear correlation with the time postsurgery (p<0.05). Multiple regression analysis showed that LOS/TBSA correlated with donor site wound protein FSR and time postsurgery (p<0.001) and the following equation describes the relationship: estimated LOS/TBSA=(FSR-12.95-1.414 x postsurgery day)/(-17.8). This equation predicted that FSR corrected for the postsurgery day when the metabolic study was conducted accounted for 67% of the variability (r(2)=0.673) in the LOS/TBSA. Donor site wound protein FSR correlated to LOS/TBSA of burn patients admitted to the intensive care unit. Measurement of protein deposition in regenerating donor site wound using stable isotope technique provides a quantitative measure of wound healing.

Intensive insulin therapy improves insulin sensitivity and mitochondrial function in severely burned children.

OBJECTIVE: To institute intensive insulin therapy protocol in an acute pediatric burn unit and study the mechanisms underlying its benefits. DESIGN: Prospective, randomized study. SETTING: An acute pediatric burn unit in a tertiary teaching hospital. PATIENTS: Children, 4-18 yrs old, with total body surface area burned > or =40% and who arrived within 1 wk after injury were enrolled in the study. INTERVENTIONS: Patients were randomized to one of two groups. Intensive insulin therapy maintained blood glucose levels between 80 and 110 mg/dL. Conventional insulin therapy maintained blood glucose < or =215 mg/dL. MEASUREMENTS AND MAIN RESULTS: Twenty patients were included in the data analysis consisting of resting energy expenditure, whole body and liver insulin sensitivity, and skeletal muscle mitochondrial function. Studies were performed at 7 days postburn (pretreatment) and at 21 days postburn (posttreatment). Resting energy expenditure significantly increased posttreatment (1476 +/- 124 to 1925 +/- 291 kcal/m(2) x day; p = .02) in conventional insulin therapy as compared with a decline in intensive insulin therapy. Glucose infusion rate was identical between groups before treatment (6.0 +/- 0.8 conventional insulin therapy vs. 6.8 +/- 0.9 mg/kg x min intensive insulin therapy; p = .5). Intensive insulin therapy displayed a significantly higher glucose clamp infusion rate posttreatment (9.1 +/- 1.3 intensive insulin therapy versus 4.8 +/- 0.6 mg/kg x min conventional insulin therapy, p = .005). Suppression of hepatic glucose release was significantly greater in the intensive insulin therapy after treatment compared with conventional insulin therapy (5.0 +/- 0.9 vs. 2.5 +/- 0.6 mg/kg x min; intensive insulin therapy vs. conventional insulin therapy; p = .03). States 3 and 4 mitochondrial oxidation of palmitate significantly improved in intensive insulin therapy (0.9 +/- 0.1 to 1.7 +/- 0.1 microm O(2)/CS/mg protein/min for state 3, p = .004; and 0.7 +/- 0.1 to 1.3 +/- 0.1 microm O(2)/CS/mg protein/min for state 4, p < .002), whereas conventional insulin therapy remained at the same level of activity (0.9 +/- 0.1 to 0.8 +/- 0.1 microm O(2)/CS/mg protein/min for state 3, p = .4; 0.6 +/- 0.03 to 0.7 +/- 0.1 microm O(2)/CS/mg protein/min, p = .6). CONCLUSION: Controlling blood glucose levels < or =120 mg/dL using an intensive insulin therapy protocol improves insulin sensitivity and mitochondrial oxidative capacity while decreasing resting energy expenditure in severely burned children.

Enhanced albumin synthesis in severely burned adults.

Albumin plays an important role in maintaining physiological homeostasis. Although decreased albumin concentration has been well described as an acute-phase response following injury, it is unclear whether the decrease is due to compromised synthesis of albumin, dilution, or imbalance between synthesis and breakdown rates, particularly after injury. We investigated changes in albumin synthesis in severely burned patients using stable isotope infusion techniques. Five patients (29 ± 3 years; 80 ± 7 kg) with burn of 48% ± 4% total body surface area (TBSA) were enrolled and studied in the ICU at the Burn Unit of the US Army Institute of Surgical Research. Five age- and sex-matched healthy volunteers (33 ± 5 years; 81 ± 6 kg) were included as controls. On the study day (13 ± 3 days after burn), a primed constant infusion (4 h) of stable isotope d5-phenlylalanine and d3-ketoisocaproic acid was given. Hourly arterial blood samples were drawn during the infusion to determine albumin synthesis rates, using gas chromatography-mass spectrometry analysis. Burned patients had higher heart and respiration rates. Plasma total protein in burn patients (4.5 ± 0.3 g · dL-1) was lower compared with controls (6.8 ± 0.2 g · dL-1). Plasma albumin concentration in burn patients (1.1 ± 0.1 g · dL-1) was also lower compared with controls (3.8 ± 0.1 g · dL-1; both P < 0.05). Albumin synthesis rate in burn patients (4.6 ± 0.2 mg · kg-1 · h-1) was enhanced compared with controls (2.2 ± 0.2 mg · kg-1 · h-1; P < 0.05). Despite the decrease in albumin concentration, albumin synthesis was enhanced in severely burned patients during the flow phase.

Crew resource management improved perception of patient safety in the operating room.

To improve safety in the operating theater, a company of aviation pilots was employed to guide implementation of preprocedural briefings. A 5-point Likert scale survey that assessed the attitudes of operating room personnel toward patient safety was distributed before and 6 months following implementation of the briefings. Using Mann-Whitney analysis, the survey showed a significant (P < .05) improvement in 2 questions (of 13) involving reporting error and 2 questions (of 11) involving patient safety climate. When analyzed by occupation, there were no significant changes for faculty physicians; for resident physicians, there was a significant improvement in 1 question (of 13) regarding error reporting. For nurses, there were significant improvements in 3 questions (of 4) involving teamwork, 1 question (of 13) involving reporting error, and 3 questions (of 11) regarding patient safety climate. These results suggest that aviation-based crew resource management initiatives lead to an improved perception of patient safety, which was largely demonstrated by nursing personnel.

Measurement of body composition in burned children: is there a gold standard?

BACKGROUND: Maintaining lean body mass (LBM) after a severe burn is an essential goal of modern burn treatment. An accurate determination of LBM is necessary for short- and long-term therapeutic decisions. The aim of this study was to compare 2 measurement methods for body composition, whole-body potassium counting (K count) and dual x-ray absorptiometry (DEXA), in a large prospective clinical trial in severely burned pediatric patients. METHODS: Two-hundred seventy-nine patients admitted with burns covering 40% of total body surface area (TBSA) were enrolled in the study. Patients enrolled were controls or received long-term treatment with recombinant human growth hormone (rhGH). Near-simultaneous measurements of LBM with DEXA and fat-free mass (FFM) with K count were performed at hospital discharge and at 6, 9, 12, 18, and 24 months post injury. Results were correlated using Pearson's regression analysis. Agreement between the 2 methods was analyzed with the Bland-Altman method. RESULTS: Age, gender distribution, weight, burn size, and admission time from injury were not significantly different between control and treatment groups. rhGH and control patients at all time points postburn showed a good correlation between LBM and FFM measurements (R(2) between 0.9 and 0.95). Bland-Altman revealed that the mean bias and 95% limits of agreement depended only on patient weight and not on treatment or time postburn. The 95% limits ranged from 0.1 +/- 2.9 kg for LBM or FFM in 7- to 18-kg patients to 16.3 +/- 17.8 kg for LBM or FFM in patients >60 kg. CONCLUSIONS: DEXA can provide a sufficiently accurate determination of LBM and changes in body composition, but a correction factor must be included for older children and adolescents with more LBM. DEXA scans are easier, cheaper, and less stressful for the patient, and this method should be used rather than the K count.

The leading causes of death after burn injury in a single pediatric burn center.

INTRODUCTION: Severe thermal injury is characterized by profound morbidity and mortality. Advances in burn and critical care, including early excision and grafting, aggressive resuscitation and advances in antimicrobial therapy have made substantial contributions to decrease morbidity and mortality. Despite these advances, death still occurs. Our aim was to determine the predominant causes of death in burned pediatric patients in order to develop new treatment avenues and future trajectories associated with increased survival. METHODS: Primary causes of death were reviewed from 144 pediatric autopsy reports. Percentages of patients that died from anoxic brain injuries, sepsis, or multi-organ failure were calculated by comparing to the total number of deaths. Data was stratified by time (from 1989 to 1999, and 1999 to 2009), and gender. Statistical analysis was done by chi-squared, Student's t-test and Kaplan-Meier for survival where applicable. Significance was accepted as P < 0.05. RESULTS: Five-thousand two-hundred-sixty patients were admitted after burn injury from July 1989 to June 2009, and of those, 145 patients died after burn injury. Of these patients, 144 patients had an autopsy. The leading causes of death over 20 years were sepsis (47%), respiratory failure (29%), anoxic brain injury (16%), and shock (8%). From 1989 to 1999, sepsis accounted for 35% of deaths but increased to 54% from 1999 to 2009, with a significant increase in the proportion due to antibiotic resistant organisms (P < 0.05). CONCLUSIONS: Sepsis is the leading cause of death after burn injury. Multiple antibiotic resistant bacteria now account for the bulk of deaths due to sepsis. Further improvement in survival may require improved strategies to deal with this problem.

Randomized controlled trial to determine the efficacy of long-term growth hormone treatment in severely burned children.

BACKGROUND: Recovery from a massive burn is characterized by catabolic and hypermetabolic responses that persist up to 2 years and impair rehabilitation and reintegration. The objective of this study was to determine the effects of long-term treatment with recombinant human growth hormone (rhGH) on growth, hypermetabolism, body composition, bone metabolism, cardiac work, and scarring in a large prospective randomized single-center controlled clinical trial in pediatric patients with massive burns. PATIENTS AND METHODS: A total of 205 pediatric patients with massive burns over 40% total body surface area were prospectively enrolled between 1998 and 2007 (clinicaltrials.gov ID NCT00675714). Patients were randomized to receive either placebo (n = 94) or long-term rhGH at 0.05, 0.1, or 0.2 mg/kg/d (n = 101). Changes in weight, body composition, bone metabolism, cardiac output, resting energy expenditure, hormones, and scar development were measured at patient discharge and at 6, 9, 12, 18, and 24 months postburn. Statistical analysis used Tukey t test or ANOVA followed by Bonferroni correction. Significance was accepted at P < 0.05. RESULTS: RhGH administration markedly improved growth and lean body mass, whereas hypermetabolism was significantly attenuated. Serum growth hormone, insulin-like growth factor-I, and IGFBP-3 was significantly increased, whereas percent body fat content significantly decreased when compared with placebo, P < 0.05. A subset analysis revealed most lean body mass gain in the 0.2 mg/kg group, P < 0.05. Bone mineral content showed an unexpected decrease in the 0.2 mg/kg group, along with a decrease in PTH and increase in osteocalcin levels, P < 0.05. Resting energy expenditure improved with rhGH administration, most markedly in the 0.1 mg/kg/d rhGH group, P < 0.05. Cardiac output was decreased at 12 and 18 months postburn in the rhGH group. Long-term administration of 0.1 and 0.2 mg/kg/d rhGH significantly improved scarring at 12 months postburn, P < 0.05. CONCLUSION: This large prospective clinical trial showed that long-term treatment with rhGH effectively enhances recovery of severely burned pediatric patients.

The synthetic rate of muscle triglyceride but not phospholipid is increased in obese rabbits.

Fat is a major energy source for skeletal muscle, and disruption of normal trafficking of fatty acids in muscle is linked to insulin resistance. We quantified muscle triglyceride (TG) and phospholipid (PL) synthesis in lean and obese rabbits by means of l-[U-(13)C(16)]palmitate infusion. Intramyocellular palmitoyl-coenzyme A was used as the precursor for rates of TG and PL synthesis, which were compared with the rates calculated using plasma nonesterified palmitate as the precursor. The muscle of obese rabbits had a greater (P < .05) combined pool of fatty acyl-coenzyme A plus fatty acyl-carnitine than lean rabbits (40.9 +/- 3.7 vs 28.6 +/- 5.3 nmol/g). Although the fractional synthetic rates of muscle TG were almost identical (0.095%/h +/- 0.016%/h vs 0.092%/h +/- 0.019%/h), the absolute synthetic rates were greater (P < .01) in the obese than in lean rabbits (39.7 +/- 9.5 vs 10.1 +/- 2.5 nmol g(-1) h(-1)) because of greater TG content in the muscle of obese rabbits. Plasma nonesterified fatty acids and TG accounted for 51% to 55% of the true precursor pool for muscle lipid synthesis in both groups, and the rest was derived from fatty acids recycled within the muscle. In contrast, the fractional and absolute synthetic rates of muscle PL as well as PL contents were comparable in the 2 groups. In conclusion, the content and synthetic rate of muscle TG rather than PL were increased in obese rabbits, which might be linked to insulin resistance. Plasma lipids and muscle lipolysis were the 2 predominate contributors to the intramyocellular fatty acyl-coenzyme A pool for lipid synthesis.