Concentration-dependent bupivacaine myotoxicity in rabbit extraocular muscle

Bupivacaine myotoxicity to the extraocular muscles, from retrobulbar or peribulbar anesthesia, has been reported after cataract surgery and other intraocular procedures. However, there are no data on the concentration-dependence of bupivacaine in causing extraocular muscle toxicity.

Six aged rabbits received different concentrations of bupivacaine (0.75% and lower) in 3 extraocular muscles, namely, superior rectus, inferior rectus, and inferior oblique muscles of each rabbit's eye. The animals were euthanized at 5 days or 1 month after the injections. Hematoxylin and eosin- and Masson trichrome-stained sections were obtained from the involved extraocular muscles after paraffin embedding.

Five days after the initial injection, the 0.75% bupivacaine-injected extraocular muscles showed extensive myonecrosis and degeneration with early-stage regenerating muscle fibers. However, muscle tissue injected with half-concentration bupivacaine (0.38%) showed scattered and significantly fewer areas of mild muscle fiber degeneration with regeneration. There were no areas of muscle tissue degeneration observed in any muscle injected with quarter-concentration bupivacaine (0.19%). At 1 month, however, only 0.75% bupivacaine-injected muscles displayed areas of regenerated muscle fiber cells with foci of scar formation. There was no visible scar formation in muscles injected with any bupivacaine concentration lower than 0.75%, or with saline, at 1 month after injection.

Extraocular muscle injection with full-strength bupivacaine (0.75%) can cause myonecrosis and degeneration acutely, with regeneration appearing by 5 days, followed by some late-stage scar formation. However, no long-term effects were observed with bupivacaine concentrations of 0.38% or 0.19%.