Fatigue after critical illness: prevalence, trajectories, and longitudinal associations in a multicenter ICU survivor follow-up program

Background: Fatigue is a common and disabling sequela among survivors of critical illness, yet its long-term trajectory and clinical correlates during recovery remain poorly understood, particularly its dynamic evolution over time and its relationship with physical and psychological domains of recovery. Methods: We conducted a prospective multicenter observational study embedded in a structured ICU follow-up program across six Italian hospitals. Outcomes were assessed during standardized in-person visits at 3, 6, 12, and 24 months after ICU discharge. Fatigue was assessed using the Fatigue Severity Scale (FSS; severe fatigue defined as FSS ≥36). Muscle strength and functional exercise capacity were evaluated using handgrip dynamometry and the six-minute walk test (6MWT), and psychological symptoms using the Hospital Anxiety and Depression Scale (HADS). Generalized linear mixed models (GLMM) with time-lagged variables were used to examine whether clinical measures at one visit were associated with severe fatigue at the subsequent visit, including prior fatigue status to account for preceding fatigue burden. Results: A total of 1,912 ICU survivors attended at least one follow-up visit, of whom 976 patients (51%) experienced severe fatigue at least once. The prevalence of severe fatigue was 336/967 (34.7%) at 3 months, 628/1,522 (41.3%) at 6 months, 434/1,135 (38.2%) at 12 months, and 64/217 (29.5%) at 24 months. Persistent severe fatigue across multiple visits was observed in 655 patients (34.3%), and individual trajectories were heterogeneous over time. In GLMM with time-lagged variable, prior fatigue status (OR 3.00, 95% CI 1.31-6.84), lower functional exercise capacity on the 6MWT (OR 0.77, 95% CI 0.61-0.95), and symptoms of anxiety (OR 6.76, 95% CI 2.01-22.68) and depression (OR 17.8, 95% CI 4.16-76.47), all measured at the preceding visit, were associated with severe fatigue at the subsequent visit. Conclusions: Severe fatigue remained common up to 24 months after ICU discharge, with heterogeneous trajectories over time and persistent severe fatigue affecting approximately one-third of survivors. Prior fatigue status, lower functional exercise capacity, and psychological distress were associated with subsequent fatigue, supporting the value of multidimensional assessment of recovery within structured ICU follow-up programs.