Abstract Rationale Skeletal muscle biopsies enable direct examination of cellular and molecular mechanisms of muscle integrity in patients with critical illness, offering insights unattainable through non-invasive assessment methods. Nonetheless, how muscle biopsies have been implemented and analyzed in critical illness has not been systematically summarized. The objective of this systematic review is to identify the methodologies and measurements acquired with muscle biopsies in patients with critical illness. Methods Six databases were electronically searched from inception to January 2025 examining original studies with upper or lower limb muscle biopsies acquired from adults admitted to the intensive care unit (ICU). Studies conducted for diagnostic purposes or in animal models were excluded. Screening, data extraction, and critical appraisal were performed in duplicate by two independent assessors using DistillerSR, in accordance with PRISMA guidelines. This review was registered in PROSPERO (CRD42024559279). Results Of 22,036 titles screened, 74 studies (n = 2,068 patients; n = 651 controls) published between 1988-2024 were included, with 48 unique patient pools. Studies were mainly observational (64 86%), from countries in Europe (61 82%) and North America (11 15%), having a median P25-P75 number of biopsies of 32 15-46 per study. In most studies, vastus lateralis (63 85%) and tibialis anterior (6 8%) were biopsied, where acquisition techniques were percutaneous/Bergström (32 43%), open/surgical (23 31%), and conchotome (12 16%). Biopsies were most often obtained during the first (38 51%), second (17 23%), and third (15 20%) week of ICU stay, while only 7 (9%) studies had biopsies after ICU discharge. The number of time-points with biopsies were 1 (n = 44 studies), 2 (n = 25 studies), 3 (n = 3 studies) and 4 (n = 2 studies). Among the 74 studies included, the most common biological muscle parameters were fiber size/type (n = 23 31%), gene expression (n = 18 24%), mitochondrial function/morphology (n = 17 23%), protein synthesis (n = 17 23%), protein degradation (n = 11 15%), inflammatory cytokines (n = 8 11%), satellite/stem cells (n = 4 5%), and extracellular matrix/collagen (n = 2 3%). Conclusions Skeletal muscle biopsies have been predominantly performed by percutaneous technique of the vastus lateralis muscle within the first weeks of ICU stay, mainly reporting myofiber size, mitochondrial function, and protein turnover findings. Variability in the timing, technique, and muscle parameters investigated limits comparability and external validity across studies and precludes translation of results into clinical practice; thus, underscores the need for standardization. Future analyses should elucidate the relevance of biological mechanisms from muscle biopsies to inform physical rehabilitation interventions. This abstract is funded by: NIH grants (R01AR081002, 5K23AR079583)
Gonzalez-Seguel et al. (2026) studied this question.