BackgroundMain contributors to adverse outcomes in severely burned pediatric patients are profound and complex metabolic changes in response to the initial injury. It is currently unknown how long these conditions persist beyond the acute phase post-injury. The aim of the present study was to examine the persistence of abnormalities of various clinical parameters commonly utilized to assess the degree hypermetabolic and inflammatory alterations in severely burned children for up to three years post-burn to identify patient specific therapeutic needs and interventions.Methodology/Principal FindingsPatients: Nine-hundred seventy-seven severely burned pediatric patients with burns over 30% of the total body surface admitted to our institution between 1998 and 2008 were enrolled in this study and compared to a cohort non-burned, non-injured children. Demographics and clinical outcomes, hypermetabolism, body composition, organ function, inflammatory and acute phase responses were determined at admission and subsequent regular intervals for up to 36 months post-burn. Statistical analysis was performed using One-way ANOVA, Student's t-test with Bonferroni correction where appropriate with significance accepted at p<0.05. Resting energy expenditure, body composition, metabolic markers, cardiac and organ function clearly demonstrated that burn caused profound alterations for up to three years post-burn demonstrating marked and prolonged hypermetabolism, p<0.05. Along with increased hypermetabolism, significant elevation of cortisol, catecholamines, cytokines, and acute phase proteins indicate that burn patients are in a hyperinflammatory state for up to three years post-burn p<0.05.ConclusionsSevere burn injury leads to a much more profound and prolonged hypermetabolic and hyperinflammatory response than previously shown. Given the tremendous adverse events associated with the hypermetabolic and hyperinflamamtory responses, we now identified treatment needs for severely burned patients for a much more prolonged time.

IntroductionSevere 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.MethodsPrimary 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.ResultsFive-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).ConclusionsSepsis 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.

SYNOPSIS Severe burn injury is followed by a profound hypermetabolic response that persists up to 24 months after injury. It is mediated by up to 50-fold elevations in plasma catecholamines, cortisol and inflammatory cells that lead to whole body catabolism, elevated resting energy expenditures and multi-organ dysfunction. All of these metabolic and physiologic derangements prevent full rehabilitation and acclimatization of burn survivors back into society. Modulation of the response by early excision and grafting of burn wounds, thermoregulation, early and continuous enteral feeding with high protein–high carbohydrate feedings and pharmacologic treatments have markedly decreased morbidity.

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. Summary Background Data Severe burns trigger a hypermetabolic response that persists for up to 2 years after burn. Propranolol given for 1 month post burn 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 >30% total body surface area burns were randomized to receive control (n = 89) or 4 mg/kg/d propranolol (n = 90) for 12 months after burn. 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 adjust for non-normality, repeated measures, and regression analyses. P <0.05 was considered significant. Results Long-term propranolol treatment significantly reduced the percent of the predicted heart rate and percent 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, following thermal injury, ameliorates the hyperdynamic, hypermetabolic, hypercatabolic, and osteopenic responses in pediatric patients. This study is registered at clinicaltrials.gov, NCT00675714.

No abstract

Background Patient survival following severe burn injury is largely determined by burn size. Modern developments in burn care have tremendously improved survival and outcomes. However, no large analysis on outcomes in pediatric burn patients with current treatment regimen exists. This study was designed to identify the burn size presently associated with significant increases in morbidity and mortality in pediatric burn patients. Methods Single center prospective observational cohort study utilizing the clinical data of severely burned pediatric patients admitted between 1998 and 2009. This study included 952 severely burned pediatric patients with burns over at least 30% of their total body surface area (TBSA). Patients were stratified by burn size in 10% increments, ranging from 30 to 100%, with a secondary assignment made according to the outcome of a receiver operating characteristic (ROC) analysis. Statistical analysis was performed using Student’s t-test, χ2 test, logistic regression and ROC analysis, as appropriate, with significance set at p<0.05. Findings All groups were comparable in age (age in years: 30–39: 6.1±5.1, 40–49: 7.1±5.2, 50–59: 7.6±5.1, 60–69: 7.2±5.1, 70–79: 8.3±5.9, 80–89: 8.4±5.6, 90–100: 9.6±5.4), and gender distribution (male: 30–39: 68%, 40–49: 64%, 50–59: 65%, 60–69: 59%, 70–79: 71%, 80–89: 62%, 90–100: 82%). Mortality (30–39: 3%, 40–49: 3%, 50–59: 7%, 60–69: 16%, 70–79: 22%, 80–89: 35%, 90–100: 55%), multi-organ failure (30–39: 6%, 40–49: 6%, 50–59: 12%, 60–69: 27%, 70–79: 29%, 80–89: 44%, 90–100: 45%), and sepsis (30–39: 2%, 40–49: 5%, 50–59: 6%, 60–69: 15%, 70–79: 13%, 80–89: 22%, 90–100: 26%), increased significantly (p<0.001) among the groups and at a threshold of 62% TBSA. Comparison of patients with burns larger than 62% with those smaller showed significant differences in inflammatory (Cytokines), acute phase (CRP) and hypermetabolic responses (REE), as well as organ function (p<0.05). Interpretation We established that in a modern pediatric burn care setting, a burn size of approximately 60% TBSA represents a crucial threshold for post-burn morbidity and mortality. Based on these findings, we recommend that pediatric burn patients over 60% TBSA burn should be immediately transferred to a specialized burn center. Furthermore, at the burn center patients should be treated with increased vigilance and enhanced therapies recognizing the increased risk for poor outcome associated with this burn size.

Objective Cardiac stress, mediated by increased catecholamines, is the hallmark of severe burn injury typified by marked tachycardia, increased myocardial oxygen consumption, and increased cardiac output. It remains one of the main determinants of survival in large burns. It is currently unknown for how long cardiac stress persists after a severe injury. Therefore, the aim of this study was to determine the extent and duration of cardiac stress after a severe burn. To determine persistence of cardiac alteration we determined cardiac parameters of all surviving patients with burns ≥ 40% total body surface area (TBSA) from 1998 to 2008. Methods One-hundred ninety-four patients were included in this study. Heart Rate (HR), mean arterial pressure (MAP), cardiac output (CO), stroke volume (SV), cardiac index (CI), and ejection fractions (EF) were measured at regular intervals from admission up to two years after injury. Rate pressure product (RPP) was calculated as a correlate of myocardial oxygen consumption. All values were compared to normal non-burned children to validate our findings. Statistical analysis was performed using log transformed ANOVA with Bonferroni correction, and Student’s t-test where applicable. Results Heart rate, cardiac output, cardiac index and RPP remained significantly elevated in burned children for up to two years when compared to normal ranges (p<0.05) indicating vastly increased cardiac stress. Ejection fraction was within normal limits for two years. Conclusions Cardiac stress persists for at least 2 years post burn and we suggest that attenuation of these detrimental responses may improve long-term morbidity.

Aggressive nutrition support is recommended following severe burn injury. Initially, such injury results in a prolonged and persistent hypermetabolic response mediated by a 10- to 20-fold elevation in plasma catecholamines, cortisol, and inflammatory mediators. This response leads to twice-normal metabolic rates, whole-body catabolism, muscle wasting, and severe cachexia. Thus, it is relevant to review the literature on nutrition in burns to adjust/update treatment. Failure to meet the increased substrate requirements may result in impaired wound healing, multiorgan dysfunction, increased susceptibility to infection, and death. Therefore, aggressive nutrition support is essential to ensure adequate burn care, attenuate the hypermetabolic response, optimize wound healing, minimize devastating catabolism, and reduce morbidity and mortality. Here, the authors provide nutrition recommendations gained from prospective trials, retrospective analyses, and expert opinions based on the authors' practices in Galveston, Texas, and Vienna, Austria.