Long-Term Outcomes and Post-Intensive Care Syndrome: Investigating the Associations Between Metabolic Signatures and Physical Functioning in Critically Ill Patients

Despite being young, healthy, and physically fit, some intensive care unit (ICU) patients experience significantly worse functional recovery after critical illness than older patients with multiple comorbidities although a poor precondition seems to be associated with worse ICU outcomes. This paradox highlights a fundamental gap in our understanding of the determinants of long-term recovery. While nonmodifiable factors such as age and pre-existing disease explain part of the variation, they cannot fully account for the wide heterogeneity in outcomes. Metabolic disturbances during critical illness, such as hypercatabolism, impaired muscle metabolism, nutritional deficits, systemic inflammation, and disruption of gut health, are likely to influence recovery trajectories, yet remain poorly characterized. Because these processes represent potentially modifiable targets, combining their evaluation with nonmodifiable patient characteristics is essential for unraveling the complex, multifactorial mechanisms underlying post-intensive care syndrome (PICS). This explorative, prospective, observational study aims to investigate the associations between metabolic signatures during the acute phase of critical illness and PICS outcomes throughout the recovery trajectory of ICU survivors, with a primary focus on physical functioning. In addition, the study explores the longitudinal course of metabolic parameters from ICU admission up to 12 months post-discharge, and whether these signatures can help identify distinct recovery phenotypes. Participants will be followed for 12 months, with study assessments at ICU admission, ICU discharge, and at 3-, 6-, and 12-months post-ICU admission.

Inclusion Criteria: * Age ≥ 18 years at time of ICU admission; * Received ventilatory support (IMV or NIV) within 48 hours after ICU admission with an expected duration of ≥48 hours during ICU stay (irrespective of ICU length of stay); OR * An expected ICU length of stay of ≥72 hours (irrespective of ventilatory support). Exclusion Criteria: * Concurrent participation in an intervention study with an anticipated therapeutic effect on PICS outcomes (physical functioning, cognitive functioning, or mental health status) * Pre-admission diagnosis of a progressive neurological disease (e.g., Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, progressive forms of multiple sclerosis) * Participants with neurological paralysis significantly affecting leg function (e.g., spinal cord injury, multiple sclerosis) * Patients receiving palliative care, with a life expectancy of \