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Clinical Trial
. 2011;6(7):e21245.
doi: 10.1371/journal.pone.0021245. Epub 2011 Jul 18.

Long-term persistance of the pathophysiologic response to severe burn injury

Affiliations
Clinical Trial

Long-term persistance of the pathophysiologic response to severe burn injury

Marc G Jeschke et al. PLoS One. 2011.

Abstract

Background: Main 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.

Patients: 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.

Conclusions: Severe 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.

Trial registration: ClinicalTrials.gov NCT00239668 NCT00673309.

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Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.

Figures

Figure 1
Figure 1. Persistently increased percent predicted REE indicate prolonged hypermetabolism (A).
REE % predicted increases upon burn injury and decreased over time but remains significantly elevated up to two years post-injury. Bars represent means; error bars correspond to S.E.M. Asterisks denote statistical difference between burned children vs. normal range, p<0.05. Body composition, weights and heights: Bone mineral content (B), LBM (C), fat (D, E) and BMD (F, G) were measured at admission and subsequent time points. DEXA analysis revealed significantly decreased values throughout the whole time period studied for BMC, LBM, and fat, p<0.05. Cardiac function and liver size post-burn: Percent predicted cardiac output (H) and cardiac index (I) were significantly increased for up to 12 months post-burn. Heart rate (J) was twice that of non-burned children for up to three years post-burn, while predicted stroke volume (K) was normal. Liver size increased by nearly two-fold upon burn injury of predicted liver size and remained elevated for the remaining of the study (L). Bars represent means; error bars correspond to S.E.M. Asterisks denote statistical difference between burned children vs. non-burned children, p<0.05.
Figure 2
Figure 2. Urinary norepinephrine (A) and epinephrine (B) are significantly increased for two and 18 months post-burn, respectively.
Twenty-four hour total urine cortisol (C) and serum cortisol (D) levels increase upon burn injury and remain significantly elevated for up to 36 months. Bars represent means; error bars correspond to S.E.M. Asterisks denote statistical difference between burned children vs. non-burned children, p<0.05.
Figure 3
Figure 3. Severe burn leads to markedly increased inflammatory response.
Fourteen cytokines measured within this study were significantly altered in response to burn injury. Particularly serum IL-6, IL-8, G-CSF and MCP-1 revealed dramatic increases. IL-12p70 and MIP-1β were not significantly altered in response to burn trauma when compared to controls. Histograms depict serum concentrations of the respective cytokine at steady state levels. Bars represent means; error bars correspond to S.E.M. Asterisks denote statistical difference between burned children vs. non-burned children, p<0.05.
Figure 4
Figure 4. Serum proteins.
Acute phase proteins and constitutive proteins are significantly altered for up to 18 months post-burn. Serum complement C3 (A), α2-macroglobulin (B), haptoglobin (C), α1-acidglycoprotein (D), and CRP (E) were significantly increased for up to nine months post-burn. Serum constitutive hepatic proteins retinol binding protein (F), pre-albumin (G), transferrin (H) markedly decreased immediately post-burn and remained diminished for up to six months post-burn. Serum apolipoprotein A1 (I) and apolipoprotein B (J) were markedly decreased for 18 and one month, respectively. Serum triglycerides (K) demonstrated significantly increased levels for nine months post-burn. Burn trauma leads to hyperglycemia and elevated fasting serum insulin concentrations, indicating insulin resistance. Histograms depict fasting serum concentrations of (L) glucose and (M) insulin. Bars represent means; error bars correspond to S.E.M. Asterisks denote statistical difference between burned children vs. non-burned children, p<0.05.
Figure 5
Figure 5. Hepatic enzymes and proteins.
Histograms depict serum concentrations of Alanin-Aminotransferase (ALT) (A), aspartat-aminotransferase (AST) (B), albumin (ALB) (C), alkaline phosphatase (ALP) (D), glutamyl transpeptidase (GGT) (E), and serum calcium concentrations (F). Serum IGF-I (G), IGFBP-3 (H), GH (I), iPTH (J), osteocalcin (K), EST (L) were significantly decreased in response to thermal injury and remained diminished for up to three years post-burn. Analysis of serum testosterone (M) and progesterone (N) revealed only moderate increases throughout the first two months post-burn. Bars represent means; error bars correspond to S.E.M. Asterisks denote statistical difference between burned children vs. non-burned children, p<0.05.

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