Therapeutic Strategies Targeting the Endocrine-Metabolic-Immunological Response to Trauma: A Systematic Review

Abstract

Background: The Endocrine-Metabolic-Immunological Response to Trauma (REMIT) encompasses a complex set of physiological adaptations triggered immediately after trauma events—such as injury, surgery, burns, or haemorrhage—with the aim of restoring homeostasis, maintaining tissue perfusion, and providing the energy needed for survival. Objective: This systematic review aims to evaluate the clinical effectiveness, associated risks, and applicability of key therapeutic strategies designed to modulate the endocrine-metabolic-immunological response to trauma (REMIT). The analysis focuses on interventions targeting the endocrine, metabolic, and immunological axes in critically ill or polytraumatized adult patients. Methodology: A systematic literature review was conducted. Searches were conducted in PubMed, SciELO, LILACS, BVS, and MEDLINE databases from January 2014 to April 2024. The review followed PRISMA guidelines. Included studies were original research (clinical trials, cohort studies, experimental models, and systematic reviews) involving adult patients with physical, surgical, or burn trauma. Filters were applied to include only full-text studies published in Portuguese, English, or Spanish, involving human adults (≥18 years). Duplicates were removed using Mendeley reference manager. Interventions analysed included glycemic control, nutrition, immunonutrition, beta-blockers, corticosteroids, antioxidants, and DAMP-targeting therapies. Selection, data extraction, and methodological quality assessment were independently conducted by two reviewers using appropriate tools (ROBIS, Cochrane, NOS). Results: Out of 117 studies screened, 15 were included, covering diverse trauma types and interventions. Early enteral nutrition, immunonutrients, and beta-blockers demonstrated the most positive clinical impact, reducing infectious complications, organ dysfunction, and hospital stay. Experimental therapies like DAMP inhibition and mitochondrial modulation showed promise in animal models. Intensive glycemic control and corticosteroid use had limited benefits and posed risks such as hypoglycemia and immunosuppression. Treatment approaches varied widely depending on trauma type and severity. Conclusion: Effective modulation of REMIT requires integrated, individualised interventions. Early enteral nutrition and immunonutrition are supported by the strongest clinical evidence. Further multicenter trials and biomarker development are needed to optimise therapeutic decision-making and improve outcomes in critical care.