<jats:title>Abstract</jats:title><jats:sec>
<jats:title>Rationale</jats:title>
<jats:p>Intensive care unit-acquired weakness (ICUAW) is common in critically ill patients, characterized by muscle weakness and physical function loss. Determining risk factors for ICUAW poses challenges due to variations in assessment methods and limited generalizability of results from specific populations, the existing literature on these risk factors lacks a clear and comprehensive synthesis.</jats:p>
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<jats:title>Objective</jats:title>
<jats:p>This overview aimed to synthesize risk factors for ICUAW, categorizing its modifiable and nonmodifiable factors.</jats:p>
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<jats:title>Methods</jats:title>
<jats:p>An overview of systematic reviews was conducted. Six relevant databases were searched for systematic reviews. Two pairs of reviewers selected reviews following predefined criteria, where bias was evaluated. Results were qualitatively summarized and an overlap analysis was performed for meta-analyses.</jats:p>
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<jats:title>Results</jats:title>
<jats:p>Eighteen systematic reviews were included, comprising 24 risk factors for ICUAW. Meta-analyses were performed for 15 factors, while remaining reviews provided qualitative syntheses. Twelve reviews had low risk of bias, 4 reviews were unclear, and 2 reviews exhibited high risk of bias. The extent of overlap ranged from 0 to 23% for the corrected covered area index. Nonmodifiable factors, including advanced age, female gender, and multiple organ failure, were consistently associated with ICUAW. Modifiable factors, including neuromuscular blocking agents, hyperglycemia, and corticosteroids, yielded conflicting results. Aminoglycosides, renal replacement therapy, and norepinephrine were associated with ICUAW but with high heterogeneity.</jats:p>
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<jats:title>Conclusions</jats:title>
<jats:p>Multiple risk factors associated with ICUAW were identified, warranting consideration in prevention and treatment strategies. Some risk factors have produced conflicting results, and several remain underexplored, emphasizing the ongoing need for personalized studies encompassing all potential contributors to ICUAW development.</jats:p>
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