Only part of the story? Mechanistic insights into dye-based spread models

Interfascial plane blocks often provide broader and longer-lasting analgesia than can be explained by the visible spread of injectate on imaging, raising questions about how local anesthetics truly distribute within tissues. In this cadaveric study, 1 quantitative analysis using high-performance liquid chromatography coupled with mass spectrometry shows that bupivacaine spreads anisotropically within fresh skeletal muscle, preferentially longitudinally along muscle fibers, and permeates fascial barriers via diffusion, despite the absence of methylene blue or iodinated contrast beyond the injection site. This anisotropic behavior was lost in frozen–thawed tissue, highlighting limitations of commonly used cadaver models. After a simulated quadratus lumborum block, clinically relevant bupivacaine concentrations were detected in the psoas major and diaphragm without visible dye spread. Together, these findings support diffusion of lipophilic local anesthetics as a key contributor to interfascial block dynamics and challenge the validity of dye-based models for explaining clinical analgesic effects.