The effects of short bouts of ergometric exercise for severely burned children in intensive care: A randomized controlled trial.

OBJECTIVE: To determine the effects of short bouts of ergometric exercises on the number of days in the burn intensive care unit (ICU), body mass, and functional ambulation. DESIGN: Multi-center, randomized controlled trial. SETTING: Burn intensive care unit. PARTICIPANTS: Children ages 7-17 with severe burns covering over 30% total body surface area (TBSA). INTERVENTION: All patients received standard of care (Control) with the experimental group receiving additional exercise with a cycle ergometer (Exercise). MAIN MEASURES: The number of days in the ICU, total weight, lean body mass (LBM), and functional ambulation were taken shortly after randomization and again within one week of the scheduled hospital discharge. Results of outcomes are expressed as median ± interquartile range (IQR), unless otherwise noted (e.g. demographics). RESULTS: Fifty-four severely burned children (n = 18 Control, n = 36 Exercise) were included. The average ± standard deviation for age was 12 ± 3 years and TBSA was 48 ± 16%. The median ± IQR ICU days for Control was 46 ± 51 days vs 31 ± 29 days for Exercise. The median total weight loss for Control was 2.2 ± 1.2 kg vs 1.8 ± 1.4 kg in Exercise. Control lost 0.75 ± 0.8 kg of LBM vs 0.46 ± 0.43 kg in Exercise. Both groups showed significant improvement in functional ambulation (p < 0.01). However, exercise did not add additional benefits. CONCLUSION: Short bouts of ergometric exercises are feasible for severely burned patients while receiving care in the ICU but did not add additional benefits.

ß-Adrenergic blockade does not impair the skin blood flow sensitivity to local heating in burned and nonburned skin under neutral and hot environments in children.

OBJECTIVE: We tested the hypothesis that propranolol, a drug given to burn patients to reduce hypermetabolism/cardiac stress, may inhibit heat dissipation by changing the sensitivity of skin blood flow (SkBF) to local heating under neutral and hot conditions. METHODS: In a randomized double-blind study, a placebo was given to eight burned children, while propranolol was given to 13 burned children with similar characteristics (mean±SD: 11.9±3 years, 147±20 cm, 45±23 kg, 56±12% Total body surface area burned). Nonburned children (n=13, 11.4±3 years, 152±15 cm, 52±13 kg) served as healthy controls. A progressive local heating protocol characterized SkBF responses in burned and unburned skin and nonburned control skin under the two environmental conditions (23 and 34°C) via laser Doppler flowmetry. RESULTS: Resting SkBF was greater in burned and unburned skin compared to the nonburned control (main effect: skin, P<.0001; 57±32 burned; 38±36 unburned vs 9±8 control %SkBFmax ). No difference was found for maximal SkBF capacity to local heating between groups. Additionally, dose-response curves for the sensitivity of SkBF to local heating were not different among burned or unburned skin, and nonburned control skin (EC50 , P>.05) under either condition. CONCLUSION: Therapeutic propranolol does not negatively affect SkBF under neutral or hot environmental conditions and further compromise temperature regulation in burned children.

Co-administration of vancomycin and piperacillin-tazobactam is associated with increased renal dysfunction in adult and pediatric burn patients.

BACKGROUND: Burn patients are prone to infections which often necessitate broad antibiotic coverage. Vancomycin is a common antibiotic after burn injury and is administered alone (V), or in combination with imipenem-cilastin (V/IC) or piperacillin-tazobactam (V/PT). Sparse reports indicate that the combination V/PT is associated with increased renal dysfunction. The purpose of this study was to evaluate the short-term impact of the three antibiotic administration types on renal dysfunction. METHODS: All pediatric and adult patients admitted to our centers between 2004 and 2016 with a burn injury were included in this retrospective review if they met the criteria of exposition to either V, V/IC, or V/PT for at least 48 h, had normal baseline creatinine, and no pre-existing renal dysfunction. Creatinine was monitored for 7 days after initial exposure; the absolute and relative increase was calculated, and patient renal outcomes were classified according to the Kidney Disease Improving Global Outcomes (KDIGO) criteria depending on creatinine increases and estimated creatinine clearance. Secondary endpoints (demographic and clinical data, incidences of septicemia, and renal replacement therapy) were analyzed. Antibiotic doses were modeled in logistic and linear multivariable regression models to predict categorical KDIGO events and relative creatinine increase. RESULTS: Out of 1449 patients who were screened, 718 met the inclusion criteria, 246 were adults, and 472 were children. Between the study cohorts V, V/IC, and V/PT, patient characteristics at admission were comparable. V/PT administration was associated with a statistically higher serum creatinine, and lower creatinine clearance compared to patients receiving V alone or V/IC in adults and children after burn injury. The incidence of KDIGO stages 1, 2, and 3 was higher after V/PT treatment. In children, the incidence of KDIGO stage 3 following administration of V/PT was greater than after V/IC. In adults, the incidence of renal replacement therapy was higher after V/PT compared with V or V/IC. Multivariate modeling demonstrated that V/PT is an independent predictor of renal dysfunction. CONCLUSION: Co-administration of vancomycin and piperacillin-tazobactam is associated with increased renal dysfunction in pediatric and adult burn patients when compared to vancomycin alone or vancomycin plus imipenem-cilastin. The mechanism of this increased nephrotoxicity remains elusive and warrants further scientific evaluation.

Correlation Between PaO2/FIO2 and Peripheral Capillary Oxygenation/FIO2 in Burned Children With Smoke Inhalation Injury.

OBJECTIVES: Determine whether the peripheral capillary oxygenation/FIO2 ratio correlates with the PaO2/FIO2 ratio in burned children with smoke inhalation injury, with the goal of understanding if the peripheral capillary oxygenation/FIO2 ratio can serve as a surrogate for the PaO2/FIO2 ratio for the diagnosis of acute respiratory distress syndrome. DESIGN: Retrospective chart review. SETTING: Shriners Hospitals for Children-Galveston. PATIENTS: All burned children with smoke inhalation injury who were admitted from 1996 to 2014 and had simultaneously obtained peripheral capillary oxygenation, FIO2 and PaO2 measurements. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Two hundred seventy-three patients (63% male, 8 ± 5 yr, 53% ± 24% total body surface area burns) were analyzed. Peripheral capillary oxygenation/FIO2 ratios were divided into four subgroups based on peripheral capillary oxygenation values (≤ 100%, ≤ 98%, ≤ 95%, and ≤ 92%). Significance was accepted at r greater than 0.81. The r (number of matches) was 0.66 (23,072) for less than or equal to 100%, 0.87 (18,932) for less than or equal to 98%, 0.89 (7,056) for less than or equal to 95%, and 0.93 (4,229) for less than or equal to 92%. In the subgroup of patients who developed acute respiratory distress syndrome, r was 0.65 (8,357) for less than or equal to 100%, 0.89 (7,578) for less than or equal to 98%, 0.89 (4,115) for less than or equal to 95%, and 0.91 (2,288) less than or equal to 92%. CONCLUSIONS: PaO2/FIO2 and peripheral capillary oxygenation/FIO2 strongly correlate in burned children with smoke inhalation injury, with a peripheral capillary oxygenation of less than 92% providing the strongest correlation. Thus, peripheral capillary oxygenation/FIO2 ratio may be able to serve as surrogate for PaO2/FIO2, especially when titrating FIO2 to achieve a peripheral capillary oxygenation of 90-95% (i.e., in the acute respiratory distress syndrome range).

Nebulized Epinephrine Limits Pulmonary Vascular Hyperpermeability to Water and Protein in Ovine With Burn and Smoke Inhalation Injury.

OBJECTIVES: To test the hypothesis that nebulized epinephrine ameliorates pulmonary dysfunction by dual action-bronchodilation (ß2-adrenergic receptor agonism) and attenuation of airway hyperemia (α1-adrenergic receptor agonism) with minimal systemic effects. DESIGN: Randomized, controlled, prospective, and large animal translational studies. SETTING: University large animal ICU. SUBJECTS: Twelve chronically instrumented sheep. INTERVENTIONS: The animals were exposed to 40% total body surface area third degree skin flame burn and 48 breaths of cooled cotton smoke inhalation under deep anesthesia and analgesia. The animals were then placed on a mechanical ventilator, fluid resuscitated, and monitored for 48 hours in a conscious state. After the injury, sheep were randomized into two groups: 1) epinephrine, nebulized with 4 mg of epinephrine every 4 hours starting 1 hour post injury, n = 6; or 2) saline, nebulized with saline in the same manner, n = 6. MEASUREMENTS AND MAIN RESULTS: Treatment with epinephrine had a significant reduction of the pulmonary transvascular fluid flux to water (p < 0.001) and protein (p < 0.05) when compared with saline treatment from 12 to 48 hours and 36 to 48 hours, respectively. Treatment with epinephrine also reduced the systemic accumulation of body fluids (p < 0.001) with a mean of 1,410 ± 560 mL at 48 hours compared with 3,284 ± 422 mL of the saline group. Hemoglobin levels were comparable between the groups. Changes in respiratory system dynamic compliance, mean airway pressure, PaO2/FiO2 ratio, and oxygenation index were also attenuated with epinephrine treatment. No considerable systemic effects were observed with epinephrine treatment. CONCLUSIONS: Nebulized epinephrine should be considered for use in future clinical studies of patients with burns and smoke inhalation injury.

Survivors versus nonsurvivors postburn: differences in inflammatory and hypermetabolic trajectories.

OBJECTIVE: To evaluate whether a panel of common biomedical markers can be utilized as trajectories to determine survival in pediatric burn patients. BACKGROUND: Despite major advances in clinical care, of the more than 1 million people burned in the United States each year, more than 4500 die as a result of their burn injuries. The ability to predict patient outcome or anticipate clinical trajectories using plasma protein expression would allow personalization of clinical care to optimize the potential for patient survival. METHODS: A total of 230 severely burned children with burns exceeding 30% of the total body surface, requiring at least 1 surgical procedure were enrolled in this prospective cohort study. Demographics, clinical outcomes, and inflammatory and acute-phase responses (serum cytokines, hormones, and proteins) were determined at admission and at 11 time points for up to 180 days postburn. Statistical analysis was performed using a 1-way analysis of variance, the Student t test, χ test, and Mann-Whitney test where appropriate. RESULTS: Survivors and nonsurvivors exhibited profound differences in critical markers of inflammation and metabolism at each time point. Nonsurvivors had significantly higher serum levels of interleukin (IL)-6, IL-8, granulocyte colony-stimulating factor, monocyte chemoattractant protein-1, C-reactive protein, glucose, insulin, blood urea nitrogen, creatinine, and bilirubin (P < 0.05). Furthermore, nonsurvivors exhibited a vastly increased hypermetabolic response that was associated with increases in organ dysfunction and sepsis when compared with survivors (P < 0.05). CONCLUSIONS: Nonsurvivors have different trajectories in inflammatory, metabolic, and acute phase responses allowing differentiation of nonsurvivors from survivors and now possibly allowing novel predictive models to improve and personalize burn outcomes.

Effects of propranolol and exercise training in children with severe burns.

OBJECTIVES: To investigate whether propranolol administration blocks the benefits induced by exercise training in severely burned children. STUDY DESIGN: Children aged 7-18 years (n = 58) with burns covering ≥30% of the total body surface area were enrolled in this randomized trial during their acute hospital admission. Twenty-seven patients were randomized to receive propranolol, whereas 31 served as untreated controls. Both groups participated in 12 weeks of in-hospital resistance and aerobic exercise training. Muscle strength, lean body mass, and peak oxygen consumption (VO2 peak) were measured before and after exercise training. Paired and unpaired Student t tests were used for within and between group comparisons, and χ(2) tests for nominal data. RESULTS: Age, length of hospitalization, and total body surface area burned were similar between groups. In both groups, muscle strength, lean body mass, and VO2 peak were significantly greater after exercise training than at baseline. The percent change in VO2 peak was significantly greater in the propranolol group than in the control group (P < .05). CONCLUSIONS: Exercise-induced enhancements in muscle mass, strength, and VO2 peak are not impaired by propranolol. Moreover, propranolol improves the aerobic response to exercise in massively burned children.

Long-term propranolol use in severely burned pediatric patients: a randomized controlled study.

OBJECTIVE: To determine the safety and efficacy of propranolol given for 1 year on cardiac function, resting energy expenditure, and body composition in a prospective, randomized, single-center, controlled study in pediatric patients with large burns. BACKGROUND: Severe burns trigger a hypermetabolic response that persists for up to 2 years postburn. Propranolol given for 1 month postburn blunts this response. Whether propranolol administration for 1 year after injury provides a continued benefit is currently unclear. METHODS: One-hundred seventy-nine pediatric patients with more than 30% total body surface area burns were randomized to control (n = 89) or 4 mg/kg/d propranolol (n = 90) for 12 months postburn. Changes in resting energy expenditure, cardiac function, and body composition were measured acutely at 3, 6, 9, and 12 months postburn. Statistical analyses included techniques that adjusted for non-normality, repeated-measures, and regression analyses. P < 0.05 was considered significant. RESULTS: Long-term propranolol treatment significantly reduced the percentage of the predicted heart rate and percentage of the predicted resting energy expenditure, decreased accumulation of central mass and central fat, prevented bone loss, and improved lean body mass accretion. There were very few adverse effects from the dose of propranolol used. CONCLUSIONS: Propranolol treatment for 12 months after thermal injury, ameliorates the hyperdynamic, hypermetabolic, hypercatabolic, and osteopenic responses in pediatric patients. This study is registered at clinicaltrials.gov: NCT00675714.

Comparison of Six-Minute Walk Test and Modified Bruce Treadmill Test in Paediatric Patients With Severe Burns: A Cross-Over Study.

OBJECTIVE: To compare the six-minute walk test and the Modified Bruce treadmill test in paediatric patients with severe burns. SUBJECTS: A total of 67 children, aged 7-17 years, with severe burns. METHODS: Participants were assigned to perform the six-minute walk test and the Modified Bruce treadmill test in randomized order on discharge from acute burn care. Primary outcome measure was heart rate. Secondary outcome measures were distance walked, Borg's CR-10 rate of perceived exertion, and maximal oxygen uptake (VO2). RESULTS: A total of 67 participants were enrolled. Thirty-eight patients completed both tests. The mean six-minute walk test maximum heart rate was 135 ± 19 bpm (range 97-180 bpm) and the mean Modified Bruce treadmill test maximum heart rate was 148 ± 24 bpm (range 100-197 bpm; p ≤ 0.05), with a weak positive correlation of R² = 0.14. The mean six-minute walk test maximum distance was 294 ± 124 m (range 55 to 522 m) while the mean Modified Bruce treadmill test maximum distance was 439 ± 181 m (range 53 to 976 m; p ≤ 0.05), with no correlation of R² = 0.006. The mean RPE CR-10 score for the six-minute walk test was 3 ± 2.5 (range 0-10) vs a mean RPE CR-10 score of 10 ± 0 for the Modified Bruce treadmill test. CONCLUSION: The Modified Bruce treadmill test challenges the cardiorespiratory system significantly more than the six-minute walk test, as reflected by maximum heart rate measurements, and the perception of effort (i.e. rate of perceived exertion) by the patient. When possible, the Modified Bruce treadmill test should be used to assess cardiovascular functional capacity. However, the six-minute walk test may be more clinically feasible for use with paediatric patients with burns, and provides information about submaximal functional exercise capacity.

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.

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.

Clearance of Indocyanine Green in Severe Pediatric Burns.

BACKGROUND: Clearance of indocyanine green dye (ICGc) reflects sinusoidal perfusion and hepatocyte cell membrane function. Thus, ICGc is a reflection of the functional reserve of intact hepatocytes. The purpose of this study was to identify predictors of ICGc in severely burned children during the acute hospitalization and at the time of discharge from the intensive care unit (ICU). A secondary aim was to determine the relationship between liver size and patient ICGc. METHODS: Twenty-six children (0.8-17 years old) with 35% or greater total body surface area burned (%TBSA-B) were included. Assessment of ICGc (in milliliters per minute per meter squared) was done during the acute hospitalization (median: 6 days after admission, median: 14 days postburn) and at the time of discharge from the ICU (median: 19 days after admission, median: 27 days postburn). Age, TBSA-B, % third-degree burns, inhalation injury, preexisting chronic malnutrition, hematocrit, liver dysfunction, and time from burn injury were incorporated in multiple linear regressions as predictive variables of ICGc. Only variables with p < 0.05 were retained in the final models. RESULTS: Time from injury and age were the strongest predictors of ICGc during the acute admission but not at the time of discharge from the ICU. Time from injury was negatively associated with ICGc, whereas age was positively associated. At the time of discharge from the ICU, ICGc was increased in proportion to the %TBSA-B, whereas inhalation injury and preexisting chronic malnutrition were associated with lower ICGc. There was no correlation between change-to-predicted liver length and ICGc. CONCLUSIONS: The intrinsic ability of the liver to extract ICG from plasma was lower in younger burned patients during the acute admission and in those with preexisting chronic malnutrition and inhalation injury at the time of discharge from the ICU. LEVEL OF EVIDENCE: Prognostic/Epidemiologic, level III.

Pathophysiologic response to severe burn injury.

OBJECTIVE: To improve clinical outcome and to determine new treatment options, we studied the pathophysiologic response postburn in a large prospective, single center, clinical trial. SUMMARY BACKGROUND DATA: A severe burn injury leads to marked hypermetabolism and catabolism, which are associated with morbidity and mortality. The underlying pathophysiology and the correlations between humoral changes and organ function have not been well delineated. METHODS: Two hundred forty-two severely burned pediatric patients [>30% total body surface area (TBSA)], who received no anabolic drugs, were enrolled in this study. Demographics, clinical data, serum hormones, serum cytokine expression profile, organ function, hypermetabolism, muscle protein synthesis, incidence of wound infection sepsis, and body composition were obtained throughout acute hospital course. RESULTS: Average age was 8 +/- 0.2 years, and average burn size was 56 +/- 1% TBSA with 43 +/- 1% third-degree TBSA. All patients were markedly hypermetabolic throughout acute hospital stay and had significant muscle protein loss as demonstrated by a negative muscle protein net balance (-0.05% +/- 0.007 nmol/100 mL leg/min) and loss of lean body mass (LBM) (-4.1% +/- 1.9%); P < 0.05. Patients lost 3% +/- 1% of their bone mineral content (BMC) and 2 +/- 1% of their bone mineral density (BMD). Serum proteome analysis demonstrated profound alterations immediately postburn, which remained abnormal throughout acute hospital stay; P < 0.05. Cardiac function was compromised immediately after burn and remained abnormal up to discharge; P < 0.05. Insulin resistance appeared during the first week postburn and persisted until discharge. Patients were hyperinflammatory with marked changes in IL-8, MCP-1, and IL-6, which were associated with 2.5 +/- 0.2 infections and 17% sepsis. CONCLUSIONS: In this large prospective clinical trial, we delineated the complexity of the postburn pathophysiologic response and conclude that the postburn response is profound, occurring in a timely manner, with derangements that are greater and more protracted than previously thought.

Gender differences in pediatric burn patients: does it make a difference?

OBJECTIVE: There is evidence that females have a better outcome in intensive care units (ICUs) when compared with males. The aim of the present study was to compare hospital course and physiologic markers between severely burned pediatric females and males. SUMMARY BACKGROUND DATA: One-hundred eighty-nine children sustaining a >or=40% total body surface area burn were divided into females (n = 76) and males (n = 113). METHODS: : Patient demographics, clinical parameters, and mortality were noted. Muscle protein synthesis was determined by stable isotope technique. Resting energy expenditure (REE) was measured by indirect calorimetry and body composition by dual x-ray absorptiometry. Serum hormones, proteins, and cytokines were determined. Cardiac function and liver size were determined by repeated ultrasound measurements. RESULTS: There were no significant differences between females and males for mortality, demographics, burn size, nutritional intake, or concomitant injuries. ICU stay was in females: 29+/-3 days whereas the stay in males was 38+/-3 days, P < 0.05. Females had a significant attenuated loss in muscle protein net balance (females: -0.028+/-0.001% vs. males: -0.05+/-0.007%) and an increase in lean body mass (Delta females: 5+/-4% vs. Delta males: -1+/-3%), P < 0.05. Percent-predicted REE was significantly decreased in females compared with males, P < 0.05. Systemic inflammatory markers and stress hormone levels were significantly decreased in females, P < 0.05. Cardiac and liver dysfunction were significantly attenuated in females compared with males, P < 0.05. CONCLUSIONS: Female burned patients exert an attenuated inflammatory and hypermetabolic response compared with males. This decrease is reflected in improved muscle protein net balance and preservation of lean body mass, which are associated with shortened hospital stay.

Are serum cytokines early predictors for the outcome of burn patients with inhalation injuries who do not survive?

INTRODUCTION: Severely burned patients suffering from inhalation injury have a significantly increased risk for mortality compared with burned patients without inhalation injury. Severe burn is associated with a distinct serum cytokine profile and alterations in cytokines that contribute to morbidity and mortality. The aim of the present study was therefore to determine whether severely burned pediatric patients with concomitant inhalation injury who had a fatal outcome exhibited a different serum cytokine profile compared with burn patients with inhalation injury who survived. Early identification followed by appropriate management of these high-risk patients may lead to improved clinical outcome. METHODS: Thirteen severely burned children with inhalation injury who did not survive and 15 severely burned pediatric patients with inhalation injury who survived were enrolled in the study. Blood was collected within 24 hours of admission and 5 to 7 days later. Cytokine levels were profiled using multiplex antibody coated beads. Inhalation injury was diagnosed by bronchoscopy during the initial surgery. The number of days on the ventilator, peak inspiratory pressure rates, arterial oxygen tension (PaO2)/fraction of inspired oxygen (FiO2) ratio and incidence of acute respiratory distress syndrome were recorded for those patients. RESULTS: Significantly altered levels of IL-4, IL-6, IL-7, IL-10, and IL-13 were detected within the first 7 days after admission in serum from burn pediatric patients with concomitant inhalation injury who did not survive when compared with similar patients who did (P < 0.05). Alterations in these cytokines were associated with increased incidence of acute respiratory distress syndrome, number of days under ventilation, increased peak inspiratory pressure, and lower PaO2/FiO2 ratio in this patient population. Multiple logistic regression analysis revealed that patients with increased IL-6 and IL-10 as well as decreased IL-7 serum levels had a significantly greater risk for mortality (P < 0.05). CONCLUSION: Early alterations in serum levels of IL-6, IL-7 and IL-10 may constitute useful predictive markers for identifying patients those who have sustained a burn with concomitant inhalation injury and who have high mortality.

Combination of recombinant human growth hormone and propranolol decreases hypermetabolism and inflammation in severely burned children.

OBJECTIVE: Recombinant human growth hormone (rhGH) is a salutary modulator of posttraumatic metabolic responses. However, rhGH administration is associated with deleterious side effects, such as hyperglycemia, increased free fatty acids, and triglycerides, which limit its use. Administration of beta-blocker attenuates cardiac work and resting energy expenditure after severe thermal injury and improves fat metabolism and insulin sensitivity. Therefore, the combination of rhGH plus propranolol appears ideal. The aim of the present study was to determine whether rhGH plus propranolol improves hypermetabolism and the inflammatory and acute phase response after severe burn without causing adverse side effects. DESIGN: Prospective randomized control trial. SETTING: Shriners Hospitals for Children. PATIENTS: Fifteen pediatric patients with burns > 40% total body surface area, 0.1-16 yrs of age, admitted within 7 days after burn. Fifteen children were matched for burn size, age, gender, inhalation injury, and infection and served as controls. INTERVENTIONS: Patients in the experimental group received rhGH (0.2 mg/kg/day) and propranolol (to decrease heart rate by 15%) for > or = 15 days. MEASUREMENTS AND MAIN RESULTS: Outcome measurements included resting energy expenditure, body composition, acute phase proteins, and cytokines. Both cohorts were similar in age, burn size, gender, and accompanying injuries. Percent predicted resting energy expenditure significantly decreased in patients receiving rhGH/propranolol (Delta -5% +/- 8%) compared with controls (Delta +35% +/- 20%) (p < .05). rhGH/propranolol administration significantly decreased serum C-reactive protein, cortisone, aspartate aminotransferase, alanine aminotransferase, free fatty acids, interleukin-6, interleukin-8, and macrophage inflammatory protein-1beta when compared with controls, while growth hormone/propranolol increased serum insulin-like growth factor-I, insulin-like growth factor binding protein-3, growth hormone, prealbumin, and interleukin-7 when compared with placebo (p < .05). CONCLUSIONS: rhGH in combination with propranolol attenuates hypermetabolism and inflammation without the adverse side effects found with rhGH therapy alone.

Estimated versus achieved maximal oxygen consumption in severely burned children maximal oxygen consumption in burned children.

PURPOSE: In burned children, exercise training increases maximal oxygen consumption (VO2 max) and can be combined with the nonspecific beta-blocker propranolol to decrease cardiac work. VO2 max is estimated if indirect calorimetry is not available. We compared measured and estimated VO2 max in severely burned children treated with or without propranolol to determine the suitability of commonly used formulas in these populations. METHODS: Patients received propranolol or placebo (control) during acute hospitalization. VO2 max was measured during a modified Bruce treadmill test at discharge and compared to values obtained using the Cooper, Bruce, American College of Sports Medicine, and Porro formulas. Pearson correlations and Bland-Altman analyses were used to compare measured and estimated values. RESULTS: Ninety-nine children (propranolol n=46,control n=53) admitted at our facility between 2003 and 2016 were analyzed. Age at burn (propranolol 12±4years, control 12±3years,p=0.893) and total body surface area burned (propranolol 44±15%,control 49±14%,p=0.090) were comparable between groups. Measured VO2 max was higher in the propranolol group (25.5±6.0mL/min/kg vs. 22.0±4.7mL/min/kg,p=0.002) and was generally lower than estimated values. Age, sex, inhalation injury, body mass index, exercise time, and maximal speed were predictive of measured VO2 max in the control group. Age, sex, and maximal speed were predictive in the propranolol group. Backward selection yielded the formula [7.63+ 2.16×sex(females=0,males=1)+0.41×age(years)+0.15×maximal speed(m/min)] (R2=0.6525). CONCLUSIONS: Propranolol seems to have beneficial effects on cardiorespiratory capacity in burned children. However, estimated VO2 max with common formulas were too high. The VO2 max formula reported here is suitable for propranolol-treated children and the Porro formula for non-propranolol-treated children.

Propranolol and Oxandrolone Therapy Accelerated Muscle Recovery in Burned Children.

INTRODUCTION: Severe burns result in prolonged hypermetabolism and skeletal muscle catabolism. Rehabilitative exercise training (RET) programs improved muscle mass and strength in severely burned children. The combination of RET with ß-blockade or testosterone analogs showed improved exercise-induced benefits on body composition and muscle function. However, the effect of RET combined with multiple drug therapy on muscle mass, strength, cardiorespiratory fitness, and protein turnover are unknown. In this placebo-controlled randomized trial, we hypothesize that RET combined with oxandrolone and propranolol (Oxprop) will improve muscle mass and function and protein turnover in severely burned children compared with burned children undergoing the same RET with a placebo. METHODS: We studied 42 severely burned children (7-17 yr) with severe burns over 30% of the total body surface area. Patients were randomized to placebo (22 control) or to Oxprop (20) and began drug administration within 96 h of admission. All patients began RET at hospital discharge as part of their standardized care. Muscle strength (N·m), power (W), V˙O2peak, body composition, and protein fractional synthetic rate and fractional breakdown rate were measured pre-RET (PRE) and post-RET (POST). RESULTS: Muscle strength and power, lean body mass, and V˙O2peak increased with RET in both groups (P < 0.01). The increase in strength and power was significantly greater in Oxprop versus control (P < 0.01), and strength and power was greater in Oxprop over control POST (P < 0.05). Fractional synthetic rate was significantly higher in Oxprop than control POST (P < 0.01), resulting in improved protein net balance POST (P < 0.05). CONCLUSIONS: Rehabilitative exercise training improves body composition, muscle function, and cardiorespiratory fitness in children recovering from severe burns. Oxprop therapy augments RET-mediated improvements in muscle strength, power, and protein turnover.

Burn size determines the inflammatory and hypermetabolic response.

BACKGROUND: Increased burn size leads to increased mortality of burned patients. Whether mortality is due to inflammation, hypermetabolism or other pathophysiologic contributing factors is not entirely determined. The purpose of the present study was to determine in a large prospective clinical trial whether different burn sizes are associated with differences in inflammation, body composition, protein synthesis, or organ function. METHODS: Pediatric burned patients were divided into four burn size groups: <40% total body surface area (TBSA) burn, 40-59% TBSA burn, 60-79% TBSA burn, and >80% TBSA burn. Demographic and clinical data, hypermetabolism, the inflammatory response, body composition, the muscle protein net balance, serum and urine hormones and proteins, and cardiac function and changes in liver size were determined. RESULTS: One hundred and eighty-nine pediatric patients of similar age and gender distribution were included in the study (<40% TBSA burn, n = 43; 40-59% TBSA burn, n = 79; 60-79% TBSA burn, n = 46; >80% TBSA burn, n = 21). Patients with larger burns had more operations, a greater incidence of infections and sepsis, and higher mortality rates compared with the other groups (P < 0.05). The percentage predicted resting energy expenditure was highest in the >80% TBSA group, followed by the 60-79% TBSA burn group (P < 0.05). Children with >80% burns lost the most body weight, lean body mass, muscle protein and bone mineral content (P < 0.05). The urine cortisol concentration was highest in the 80-99% and 60-79% TBSA burn groups, associated with significant myocardial depression and increased change in liver size (P < 0.05). The cytokine profile showed distinct differences in expression of IL-8, TNF, IL-6, IL-12p70, monocyte chemoattractant protein-1 and granulocyte-macrophage colony-stimulating factor (P < 0.05). CONCLUSION: Morbidity and mortality in burned patients is burn size dependent, starts at a 60% TBSA burn and is due to an increased hypermetabolic and inflammatory reaction, along with impaired cardiac function.

Respiratory management of inhalation injury.

Advances in the care of patients with major burns have led to a reduction in mortality and a change in the cause of their death. Burn shock, which accounted for almost 20 percent of burn deaths in the 1930s and 1940s, is now treated with early, vigorous fluid resuscitation and is only rarely a cause of death. Burn wound sepsis, which emerged as the primary cause of mortality once burn shock decreased in importance, has been brought under control with the use of topical antibiotics and aggressive surgical debridement. Inhalation injury has now become the most frequent cause of death in burn patients. Although mortality from smoke inhalation alone is low (0-11 percent), smoke inhalation in combination with cutaneous burns is fatal in 30 to 90 percent of patients. It has been recently reported that the presence of inhalation injury increases burn mortality by 20 percent and that inhalation injury predisposes to pneumonia. Pneumonia has been shown to independently increase burn mortality by 40 percent, and the combination of inhalation injury and pneumonia leads to a 60 percent increase in deaths. Children and the elderly are especially prone to pneumonia due to a limited physiologic reserve. It is imperative that a well organized, protocol driven approach to respiratory care of inhalation injury be utilized so that improvements can be made and the morbidity and mortality associated with inhalation injury be reduced.