Oxidative Stress, Telomere Length, and Post-Intensive Care Syndrome in Mechanically Ventilated ICU Survivors

ICU survivors are at increased risk for persistent physical, cognitive, and psychological impairments, collectively known as Post-Intensive Care Syndrome (PICS). Critically ill patients, especially those on mechanical ventilation, experience increased oxidative stress burden, potentially contributing to telomere shortening. However, the relationship between oxidative stress, telomere attrition, and PICS-related outcomes remains unclear. Our objective was to examine associations among oxidative stress markers, telomere length, clinical characteristics, and PICS-related outcomes in mechanically ventilated ICU survivors. A cross-sectional study design was used. Blood samples were collected at two timepoints: study enrollment and within 48 hr of ICU discharge. PICS-related outcome measures were assessed within 48 hr of ICU discharge. Oxidative stress markers-including plasma protein carbonyls, vitamin C, reduced-to-oxidized glutathione ratio (GSH:GSSG), and total antioxidant capacity (TAC)-were quantified via ELISA. Three oxidative stress indices were calculated: vitamin C/GSH:GSSG, TAC/GSH:GSSG, and protein carbonyls/GSH:GSSG. Telomere length was determined using RT-qPCR. Clinical data included APACHE III and SOFA scores, ICU and hospital length of stay (LOS), and duration of mechanical ventilation. PICS-related outcomes included grip and foot strength, National Institutes of Health (NIH) Toolbox Cognition and Emotion assessments, and the Connor-Davidson Resilience Scale. Pearson's correlations were performed. Twenty-one participants were included in the final analysis. Plasma antioxidant status positively correlated with muscle strength and psychological resilience. Elevated plasma oxidant levels were associated with poorer cognitive outcomes. ICU LOS and duration of mechanical ventilation negatively correlated with muscle strength and cognitive performance. No significant correlations were observed between telomere length changes and PICS-related outcomes. Oxidative stress during acute critical illness may impede recovery and contribute to PICS. The lack of short-term associations with telomere length suggests that telomere-related effects on PICS may, possibly, become apparent over a longer post-ICU period.