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Rethinking Muscle Wasting in Critical Illness: A Systematic Review and Meta-Analysis of Myofiber Size and Protein
Felipe González-Seguel1,2,3, Cayla M Robinson4, Camilo Caceres-Parra3
1Department of Physical Therapy, College of Health Sciences, University of Kentucky, Lexington, KY.
Critical Care Medicine
|August 7, 2026
Summary
Skeletal muscle dysfunction in critical illness involves myofiber atrophy and increased protein degradation, but not reduced muscle protein synthesis. This study analyzes biological findings and meta-analyzes muscle mass and turnover in critically ill adults.
Area of Science:
- Biomedical Science
- Critical Care Medicine
- Skeletal Muscle Physiology
Background:
- Critical illness is associated with significant skeletal muscle dysfunction.
- Understanding the underlying biological mechanisms is crucial for patient recovery and management.
- Previous research indicates muscle wasting, but specific molecular pathways require detailed analysis.
Purpose of the Study:
- To identify and synthesize biological findings related to skeletal muscle dysfunction in critically ill adults.
- To meta-analyze myofiber cross-sectional area and protein turnover variables in this patient population.
Main Methods:
- Systematic literature search of six databases from inception to January 2025.
- Inclusion of original studies reporting biological findings from skeletal muscle biopsies of critically ill adults.
- Data extraction included bibliometrics, patient/control characteristics, and biological findings; random-effects meta-analyses were performed for myofiber size and protein turnover.
Main Results:
- Seventy-five studies (n=2,023 patients) revealed predominant type II myofiber atrophy, necrosis, mitochondrial dysfunction, inflammation, fibrosis, and upregulated ubiquitin-proteasome/autophagy pathways.
- Meta-analysis showed significantly lower myofiber cross-sectional area in critically ill patients compared to controls (22% reduction).
- Protein synthesis was not significantly different, but protein degradation markers were significantly higher in critically ill patients.
Conclusions:
- Muscle wasting in critical illness is a complex process involving multiple biological disturbances.
- Critically ill patients exhibit reduced myofiber size and elevated protein degradation.
- Muscle protein synthesis rates do not significantly differ from non-ICU controls, suggesting degradation is the primary driver of muscle loss.
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