In Vitro Toxicity of Local Anesthetics and Corticosteroids on Chondrocyte and Synoviocyte Viability and Metabolism

Abstract

Objective:There is growing concern that intra-articular injection of local anesthetic and/or corticosteroids may cause significant morbidity, including potential toxicity to chondrocytes and synoviocytes, after even a single exposure. We demonstrate that full thickness canine chondral and synovial samples exposed to various local anesthetics and corticosteroids exhibit decreased loss of cell viability compared with prior in vitro studies using monolayer culture, due to the protective effects of intact extracellular matrix and cell heterogeneity.Methods:Full-thickness cartilage and synovial explants were obtained from canine cadavers and exposed in culture media to the following for 24 hours: 1% lidocaine, 0.5% lidocaine, 0.25% bupivacaine, 0.125% bupvacaine, 0.0625% bupivacaine, betamethasone acetate, methylprednisolone acetate, triamcinolone acetonide, or culture media only (control). Cell viability was determined on days 1 and 7 of culture using a microscopic live-dead and alamar blue metabolic assays.Results:Complete loss of chondrocyte and synoviocyte viability was noted in the 1% and 0.5% lidocaine group, 0.25% and 0.125% bupivacaine group, betamethasone group, and methylprednisolone groups after 1 and 7 days of culture. Treatment with 0.0625% bupivacaine and triamcinolone demonstrated no decrease in cell viability or metabolism when compared to negative control.Conclusions:In this canine explant model, 1% and 0.5% lidocaine, 0.25% and 0.125% bupivacaine, betamethasone acetate, and methylpresdnisolone acetate were severely chondrotoxic and synoviotoxic after a single exposure, despite intact extracellular matrix. In contrast, chondrocytes and synoviocytes exposed to 0.0625% bupivacaine and triamcinolone remained viable after treatment. Further in vivo study is needed before definitive recommendations can be made.

Erector spinae plane block for the management of chronic shoulder pain: a case report

“…2,3 This latter strategy may be preferable where characteristics of neuropathic pain are present, as well as to avoid concerns of chondrotoxicity from repeated intraarticular injections. 11,12 The ESP block was originally described for management of thoracic pain with injection at the T5 transverse process. [4][5][6] Its therapeutic effect is attributed to the cranial-caudal spread of local anesthetic over multiple vertebral levels in the musculofascial plane deep to the erector spinae muscle, accompanied by diffusion anteriorly into the contiguous paravertebral and intercostal spaces, where the local anesthetic then acts on the ventral and dorsal rami of spinal nerves.…”

Local anaesthetics or their combination with morphine and/or magnesium sulphate are toxic for equine chondrocytes and synoviocytes in vitro

“…The present study demonstrates that bupivacaine at a concentration of 0.22% is harmful for articular equine synoviocytes but its negative effects are less pronounced on chondrocytes. A protective effect from the existence of intact extracellular matrix on chondrocytes from the cartilage explant has been previously suggested [ 6 , 14 ], although this was recently questioned on an experimental canine model [ 10 ]. Local anaesthetics have drug-, dose- and time-dependent cytotoxic effects [ 5 , 10 , 35 – 37 ].…”

“…A protective effect from the existence of intact extracellular matrix on chondrocytes from the cartilage explant has been previously suggested [ 6 , 14 ], although this was recently questioned on an experimental canine model [ 10 ]. Local anaesthetics have drug-, dose- and time-dependent cytotoxic effects [ 5 , 10 , 35 – 37 ]. Bupivacaine 0.0625% did not cause cell death in canine cartilage and synovium explants [ 10 ] and varying toxicity has been observed for bupivacaine concentrations in the range of 0.125–0.25% [ 2 , 5 , 10 , 35 ].…”

Therapeutic Review of Methylprednisolone Acetate Intra‐Articular Injection in the Management of Osteoarthritis of the Knee – Part 2: Clinical and Procedural Considerations

“…However, evidence is lacking on additional benefits of LA on outcomes (Galloway and Bukhari ; Smith, ), and there is some association with increased adverse events (Nazir and Holdcroft, ). There are findings of chondrotoxicity with LAs alone and in combination with corticosteroids, including MPA (Braun et al, ; Dragoo et al, ; Rao et al, : Seshadri et al, ; Sherman et al, ). Although Ravnihar et al () reported contrary findings, judicious use in early disease is suggested.…”