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      Long-Term Persistance of the Pathophysiologic Response to Severe Burn Injury

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          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.

          Methodology/Principal Findings

          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.

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          Most cited references74

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          The effect of insulin on the disposal of intravenous glucose. Results from indirect calorimetry and hepatic and femoral venous catheterization.

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            Cytokines and the hepatic acute phase response.

            H Moshage (1997)
            The acute phase response is an orchestrated response to tissue injury, infection or inflammation. A prominent feature of this response is the induction of acute phase proteins, which are involved in the restoration of homeostasis. Cytokines are important mediators of the acute phase response. Uncontrolled and prolonged action of cytokines is potentially harmful, therefore mechanisms exist which limit the activity of cytokines; these include soluble cytokine receptors and receptor antagonists. The cytokine signal is transmitted into the cell via membrane-bound receptors. Different intracellular signalling pathways are activated by different cytokine-receptor interactions. Eventually, cytokine-inducible transcription factors interact with their response elements in the promotor region of acute phase genes and transcription is induced. Systemic inflammation results in a systemic acute phase response. However, local inflammatory or injurious processes in the liver may also induce an acute phase response, for example after partial hepatectomy and during hepatic fibrosis. The acute phase proteins induced in these conditions probably act to limit proteolytic and/or fibrogenic activity and tissue damage. The possible function of the acute phase protein alpha 2-macroglobulin in hepatic fibrosis is discussed in some detail.
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              Stress-induced hyperglycemia.

              Stress hyperglycemia is common and likely to be associated with at least some of the same complications as hyperglycemia in true diabetes mellitus, such as poor wound healing and a higher infection rate. The predominant cause is the intense counterregulatory hormone and cytokine responses of critical illness, often compounded by excessive dextrose administration, usually as TPN. Although randomized data suggesting benefit of controlling hyperglycemia in hospitalized patients are paltry, prospective controlled trials are feasible and should be initiated. In the interim, the practice at the authors' institution is to use insulin to lower plasma glucose concentrations to a safe range of 150 mg/dL to 200 mg/dL in all patients.
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                Author and article information

                Contributors
                Role: Editor
                Journal
                PLoS One
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, USA )
                1932-6203
                2011
                18 July 2011
                : 6
                : 7
                : e21245
                Affiliations
                [1 ]Shriners Hospitals for Children, University of Texas Medical Branch, Galveston, Texas, United States of America
                [2 ]Department of Surgery, University of Texas Medical Branch, Galveston, Texas, United States of America
                [3 ]Sealy Center for Molecular Medicine and the Institute for Translational Sciences, University of Texas Medical Branch, Galveston, Texas, United States of America
                [4 ]Department of Dermatology and Allergology, Ludwig Maximilians University, Munich, Germany
                [5 ]Division of Plastic Surgery, Department of Surgery and Sunnybrook Health Sciences Centre, University of Toronto, Toronto, Canada
                Rutgers University, United States of America
                Author notes

                Conceived and designed the experiments: MGJ GGG DNH. Performed the experiments: MGJ GGG GAK FNW RK OES DNH RPM. Analyzed the data: MGJ GGG CCF GAK FNW RK OES DNH RPM. Contributed reagents/materials/analysis tools: MGJ GGG CCF GAK FNW RK OES DNH. Wrote the paper: MGJ GGG DNH. Proofread the manuscript: RPM.

                Article
                PONE-D-11-04378
                10.1371/journal.pone.0021245
                3138751
                21789167
                8f970230-2f34-46c0-8597-1cc14ae1b803
                Jeschke et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
                History
                : 28 February 2011
                : 24 May 2011
                Page count
                Pages: 12
                Categories
                Research Article
                Biology
                Anatomy and Physiology
                Immune Physiology
                Cytokines
                Biochemistry
                Metabolism
                Developmental Biology
                Molecular Development
                Cytokines
                Immunology
                Immune System
                Cytokines
                Immunity
                Inflammation
                Microbiology
                Immunity
                Inflammation
                Molecular Cell Biology
                Cell Division
                Cytokinesis
                Medicine
                Anatomy and Physiology
                Immune Physiology
                Cytokines
                Clinical Immunology
                Immune System
                Cytokines
                Immunity
                Inflammation
                Critical Care and Emergency Medicine
                Pediatric Critical Care
                Dermatology
                Burn Management
                Diagnostic Medicine
                Pathology
                Anatomical Pathology
                Surgical Pathology
                Metabolic Disorders
                Pediatrics
                Pediatric Critical Care
                Surgery
                Burn Management
                Pediatric Surgery
                Trauma Surgery

                Uncategorized
                Uncategorized

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