Dynamic muscle loss and metabolic dysregulation in sepsis-associated muscle wasting: an integrated ultrasound and metabolomics study

J J, Jinyuan Li, Xuepeng Bai, Hanyu Mai, Tao Feng, Jianjun Yang, Huan Ding

Objective This study aimed to investigate early changes in the rectus femoris muscle during sepsis-associated muscle wasting (SAMW) and their association with metabolic dysregulation through a dynamic analysis of ultrasound texture features and metabolomics. Methods In this prospective observational study, adults with sepsis underwent ultrasound of the right rectus femoris on intensive care unit (ICU) days 1, 4, and 7 to measure rectus femoris cross-sectional area (RF-CSA), muscle layer thickness (RF-MLT), and gray-level co-occurrence matrix texture features. Linear mixed-effects models were used to assess group, time, and group-by-time effects, and repeated-measures correlations were used to test longitudinal associations with metabolic/inflammatory biomarkers. Untargeted metabolomics was performed in the SAMW subgroup. Results Of the 751 patients screened, 60 were included, and 16 (26.7%) developed SAMW. A significant group-by-time interaction was observed only for RF-CSA ( p = 0.031), which declined in SAMW (slope −0.121, SE 0.039; p = 0.0024). Patients with sepsis showed reduced systemic inflammation during the first week in the ICU; however, SAMW featured persistent muscle wasting, possibly driven by ongoing glucose/lipid dysregulation and hypercatabolism. RF-MLT was negatively correlated with low-density lipoprotein ( r = −0.42, p < 0.001), and RF-CSA with total cholesterol ( r = −0.25, p < 0.05). Texture standard deviation correlated positively with glucose ( r = 0.29, p < 0.01) and negatively with interleukin-6 ( r = −0.23, p < 0.05). Metabolomics identified 29 metabolites that progressively decreased from controls to SAMW on days 1 and 7, with enrichment of fatty acid pathways; docosahexaenoic acid and arachidonic acid emerged as key differential metabolites. Conclusion Although systemic inflammation gradually decreased during the first week of ICU stay in patients with sepsis, those who developed SAMW showed persistent loss of muscle mass associated with metabolic dysregulation. Clinical trial registration The study was registered at ClinicalTrials.gov (registration no.: ChiCTR2400092420).