Pathophysiology of severe burn injuries: new therapeutic opportunities from a systems perspective

Dobson, Geoffrey P., Morris, Jodie L., and Letson, Hayley L. (2024) Pathophysiology of severe burn injuries: new therapeutic opportunities from a systems perspective. Journal of Burn Care and Research. irae049. (In Press)

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Abstract

Severe burn injury elicits a profound stress response with the potential for high morbidity and mortality. If polytrauma is present, patient outcomes appear to be worse. Sex-based comparisons indicate females have worse outcomes than males. There are few effective drug therapies to treat burn shock and secondary injury progression. The lack of effective drugs appears to arise from the current treat-as-you-go approach rather than a more integrated systems approach. In this review, we present a brief history of burns research and discuss its pathophysiology from a systems’ perspective. The severe burn injury phenotype appears to develop from a rapid and relentless barrage of damage-associated molecular patterns (DAMPs), pathogen-associated molecular patterns (PAMPs) and neural afferent signals, which leads to a state of hyperinflammation, immune dysfunction, coagulopathy, hypermetabolism and intense pain. We propose that if the central nervous system (CNS) control of cardiovascular function and endothelial-glycocalyx-mitochondrial coupling can be restored early, these secondary injury processes may be minimized. The therapeutic goal is to switch the injury phenotype to a healing phenotype by reducing fluid leak and maintaining tissue O2 perfusion. Currently, no systems-based therapies exist to treat severe burns. We have been developing a small-volume fluid therapy comprising adenosine, lidocaine and magnesium (ALM) to treat hemorrhagic shock, traumatic brain injury and sepsis. Our early studies indicate that the ALM therapy holds some promise in supporting cardiovascular and pulmonary functions following severe burns. Future research will investigate the ability of ALM therapy to treat severe burns with polytrauma and sex disparities, and potential translation to humans.

Item ID: 82520
Item Type: Article (Research - C1)
ISSN: 1559-0488
Keywords: ALM, adenosine, lidocaine, magnesium, trauma, military, pathophysiology, fluids, shock
Copyright Information: © The Author(s) 2024. Published by Oxford University Press on behalf of the American Burn Association. This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial License (https://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com
Funders: US Department of Defense (USAMRAA Award)
Projects and Grants: USAMRAA Award W81XWH-22-1-0556, Log Number MB210101
Date Deposited: 04 Apr 2024 00:10
FoR Codes: 32 BIOMEDICAL AND CLINICAL SCIENCES > 3202 Clinical sciences > 320207 Emergency medicine @ 50%
32 BIOMEDICAL AND CLINICAL SCIENCES > 3208 Medical physiology > 320803 Systems physiology @ 50%
SEO Codes: 20 HEALTH > 2001 Clinical health > 200199 Clinical health not elsewhere classified @ 100%
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