Pathophysiology of Severe Burn Injuries: New Therapeutic Opportunities From a Systems Perspective.
J Burn Care Res
; 45(4): 1041-1050, 2024 Aug 06.
Article
em En
| MEDLINE
| ID: mdl-38517382
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, pathogen-associated molecular patterns, 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 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.
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Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Queimaduras
Limite:
Female
/
Humans
/
Male
Idioma:
En
Revista:
J Burn Care Res
Assunto da revista:
TRAUMATOLOGIA
Ano de publicação:
2024
Tipo de documento:
Article
País de afiliação:
Austrália