Autophagic Activity in Peripheral Blood Mononuclear Cells of Critically Ill Patients With and Without Intensive Care Unit-Acquired Weakness: A Cross-Sectional Observational Study

Introduction This study aimed to compare autophagic activity in peripheral blood mononuclear cells (PBMCs) between intensive care unit-acquired weakness (ICU-AW) and non-ICU-AW patients, and to evaluate phase-specific differences and their associations with immune and inflammatory profiles. Methods This single-center, cross-sectional observational study included 42 patients who required mechanical ventilation for more than 48 hours between April 2020 and March 2022. PBMCs were collected within 48 hours of ICU admission (early phase) and on day 7 (late phase). Autophagic activity, assessed by mean fluorescence intensity (MFI), was evaluated via flow cytometry using DAPGreen (Dojindo, Kumamoto, Japan). ICU-AW was diagnosed based on a Medical Research Council sum score of less than 48 points. Results Among the 42 patients, 14 (33.3%) developed ICU-AW. PBMCs from ICU-AW patients demonstrated significantly lower autophagic activity in the early phase compared to non-ICU-AW patients (non-ICU-AW vs. ICU-AW patients: MFI of granulocytes, 30.9 (22.6, 51.7) vs. 20.4 (18.0, 22.6), p < 0.001; and lymphocytes, 94.6 (64.9, 123.0) vs. 65.2 (58.0, 77.5), p = 0.011). In contrast, excessive autophagic activity was observed in some ICU-AW cases during the late phase (MFI of granulocytes, 21.0 (17.9, 22.9) vs. 33.8 (22.9, 56.0), p < 0.001; and lymphocytes, 67.5 (54.4, 93.5) vs. 106.2 (64.6, 124.5), p = 0.012). The proportion of monocytes was also significantly reduced in the ICU-AW group. These findings suggest that impaired early-phase autophagy may contribute to ICU-AW pathogenesis, whereas delayed overactivation could be associated with persistent inflammation and impaired muscle recovery. Conclusion Autophagic activity in PBMCs exhibited temporal alterations in patients with ICU-AW. These findings suggest a potential association between dysregulated autophagy and muscle dysfunction in critically ill patients. Further research is needed to explore whether modulation of autophagy could inform future preventive strategies.