Intensive Care Unit Acquired Weakness as a Modifiable Organ Dysfunction? A Narrative Review of Evolving Diagnostic and Therapeutic Concepts

Intensive Care Unit Acquired Weakness (ICUAW) is a highly prevalent neuromuscular complication affecting around 40% of critically ill patients, rising to over 80% in high-risk cohorts. It is independently associated with prolonged mechanical ventilation, increased intensive care unit (ICU) and hospital length of stay, elevated mortality (in-hospital, 1-year, and 5-year), higher healthcare costs, and long-term functional impairment. ICUAW is clinically defined by symmetric flaccid tetraparesis, frequently involving respiratory muscles, and exhibits significant pathobiological heterogeneity. Further subclassification is based on neurotopographic patterns: Critical Illness Polyneuropathy (CIP), Myopathy (CIM), and Polyneuromyopathy (CIPNM). Diagnosis typically relies on the Medical Research Council (MRC) Sum Score, with a threshold of <48 indicating clinically relevant weakness. While adjunct modalities such as electromyography/nerve conduction studies support assessment, their utility may be limited by patient cooperation and availability. Preventive strategies center on modifiable metabolic factors. Caloric and protein deficits exacerbate catabolism, while overfeeding—linked to anabolic resistance and stress hyperglycemia—also impairs recovery. To date, pharmacologic interventions remain inconclusive. However, early mobilization and neuromuscular electrical stimulation are promising non-pharmacologic strategies. The multifactorial and heterogeneous pathophysiology of ICUAW highlights the need for a biologically refined definition that can guide future targeted therapeutic interventions. Comprehensive multimodal strategies, together with structured long-term follow-up in Post-Intensive Care Syndrome (PICS) clinics, are essential for improving outcomes in this prevalent complication of critical care.