Clinical and histological safety assessment of repeated intra-articular sevoflurane injections into knee joints of Sprague-Dawley rats

Objectives We investigated the effects of repeated intra-articular injections of liquid sevoflurane to articular structures, as this inhalational anesthetic is being repurposed as an antimicrobial agent, which would make sevoflurane a novel alternative for the treatment of septic arthritis. Methods The left knees of nine Sprague-Dawley rats were injected with 150 μL of liquid sevoflurane for five consecutive days, whereas the right knees were injected with the same volume of saline to serve as controls. Animals were examined daily for clinical signs of local and systemic toxic effects attributable to sevoflurane. Rats were euthanized in groups of three at days 7, 14, and 35 after the first injection, and left and right knees were sent for histological assessment. Results Local signs on knees consisted of transient bilateral scabs, and an unexpected subcutaneous emphysema affecting only left knees, which was attributed to sevoflurane. No rat presented with limp, and animal welfare was good during the study period. Two out of the three left knees from rats sacrificed at day 7 showed mild histological changes, specifically a mild infiltration of lymphocytes. All other seven left knees as well as all nine right knees were completely normal at histological examination. Conclusion We concluded that repeated intra-articular injections of sevoflurane seemed safe for articular structures in noninfected knees. Further studies focused on the safety of intra-articular sevoflurane in infected knees, as well as on its effectiveness for the treatment of septic arthritis are warranted.