Background In this systematic review, we summarize the aetiology as well as the current knowledge regarding thermo(dys)regulation and hypothermia after severe burn trauma and aim to present key concepts of pathophysiology and treatment options. Severe burn injuries with >20% total body surface area (TBSA) affected commonly leave the patient requiring several surgical procedures, prolonged hospital stays and cause substantial changes to body composition and metabolism in the acute and long-term phase. Particularly in severely burned patients, the loss of intact skin and the dysregulation of peripheral and central thermoregulatory processes may lead to substantial complications. Methods A systematic and protocol-based search for suitable publications was conducted following the PRISMA guidelines. Articles were screened and included if deemed eligible. This encompasses animal-based in vivo studies as well as clinical studies examining the control-loops of thermoregulation and metabolic stability within burn patients Results Both experimental animal studies and clinical studies examining thermoregulation and metabolic functions within burn patients have produced a general understanding of core concepts which are, nonetheless, lacking in detail. We describe the wide range of pathophysiological alterations observed after severe burn trauma and highlight the association between thermoregulation and hypermetabolism as well as the interactions between nearly all organ systems. Lastly, the current clinical standards of mitigating the negative effects of thermodysregulation and hypothermia are summarized, as a comprehensive understanding and implementation of the key concepts is critical for patient survival and long-term well-being. Conclusions The available in vivo animal models have provided many insights into the interwoven pathophysiology of severe burn injury, especially concerning thermoregulation. We offer an outlook on concepts of altered central thermoregulation from non-burn research as potential areas of future research interest and aim to provide an overview of the clinical implications of temperature management in burn patients.

Introduction Our clinical research unveiled chronic heart failure with preserved ejection fraction (HFpEF) as a long-term sequel in survivors of severe pediatric burn injury due to a yet unknown molecular pathomechanism. Applying a standardized rat model, we systematically determined the pathophysiological impact of burn injury on long-term cardiac performance to uncover systemic and molecular pathomechanisms that may cause post-burn HFpEF development. Methods Male adolescent SD-rats were subjected to a 60 % total body surface area (TBSA) full-thickness burn- or sham-trauma and subsequently characterized after burn-injury by serial transthoracic echocardiography, bulk myocardial next-generation sequencing and proteomics as well as RT-PCR, immuno-blotting (IB), histology and plasma proteomics for cardiac performance and molecular alterations, respectively, at 3, 7, 30 and 90days. Results In comparison to the sham-group (SG), animals from the burn-group (BG) recapitulated typical post-burn clinical traits, such as significant loss in body weight (BG 27 % less than SG at 30d, p< 0.05) or skeletal muscle wasting (27 % less at 30d, p< 0.05) in accord with elevated molecular atrophy markers. We show post-burn cardiac muscle wasting (BG 22 % less at 30d, p< 0.05) and persistent markers of cardiac dysfunction in accord with significant histological cardiomyocyte hypotrophy (BG -8 % at 30d, p< 0.05) and significantly diminished left ventricular (LV) global longitudinal strain and isovolumic relaxation time in BGs, while LV-EF remained unchanged. Weighted gene network correlation analysis from bulk myocardial NGS and clinical traits related activation of immunological and pro-fibrotic pathways in post-burn injury hearts to cardiac dysfunction in BGs. Subsequent RT-PCR and histology confirmed significant myocardial accumulation of cardio-depressive damage associated molecular patterns (i.e., S100A8 and A9) and infiltration by granulocytes and monocytes as well as significant LV fibrosis. Serial plasma proteomic analysis indicated elevated plasma levels of S100A8 and A9 and other heart failure markers that mirrored similar changes in human post-burn plasma samples. Conclusions Here we report the development of HFpEF as a novel systemic consequence of severe burn injury in a rodent model, which warrants further mechanistic and translational studies. Cardiac inflammation and fibrosis are known to negatively impact cardiac performance and may be mechanistic key findings that will guide further therapeutic studies and subsequent validation of post-burn heart failure biomarkers Applicability of Research to Practice This model is part of a translational and interdisciplinary experimental and clinical effort to inform pathophysiology and mechanistics of long-term heart failure in burn patients. Echocardiographic data and parameters from this model are currently being used to evaluate adult survivors of severe burn injury for signs of HFpEF.

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