Synovial fluid bupivacaine concentrations following single intra‐articular injection in normal and osteoarthritic canine stifles

Barry, Sabrina L.; Martinez, Steven A.; Davies, Neal M.; Remsberg, Connie M.; Sayre, Casey L.; Bachelez, Andreas

doi:10.1111/jvp.12158

Cited by 11 publications

(14 citation statements)

References 18 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In this study, low concentrations of SFB similar to the concentration achieved previously after a single intraarticular stifle injection 15 resulted in chondrotoxicity similar to that in 0.9% saline assessed with short-term MTT assay and long-term clonogenic assay techniques. We therefore accepted our hypothesis that low concentrations of SFB are not chondrotoxic in vitro.…”

Section: Discussionsupporting

confidence: 60%

Effect of bupivacaine concentration and formulation on canine chondrocyte viability in vitro

2021

View full text Add to dashboard Cite

Objective: To quantitate bupivacaine concentration and formulation effects on chondrocyte viability in vitro. Study design: Controlled laboratory study. Sample population: Primary canine chondrocyte isolates. Methods: Cell passage 3 and 4 canine chondrocytes were exposed to 0.9% saline; canine chondrocyte growth medium; 0.4, 0.5, 0.6, 1.5, 2.5, 3.5, or 5 mg/ mL preservative-free standard formulation bupivacaine (SFB); or 13.3 or 6.65 mg/mL liposomal encapsulated bupivacaine (LEB) for 1 hour. Chondrocyte viability and clonogenicity were quantitated with 3-(4,5-dimethylthiazol-2-31 yl)-2,5-diphenyltetrazolium bromide (MTT) and clonogenic assays, respectively. Differences among concentrations and formulations were assessed with Kruskal-Wallis and Dwass-Steel-Critchlow-Fligner post hoc tests. Results: Growth medium had the highest cell viability based on MTT metabolism. Similarly, all LEB concentration groups had higher cell viability compared with SFB concentration cells treated with 3.5 or 5 mg/mL SFB (P < .03). Among SFB concentrations, cell viability was higher at 0.6 mg/mL compared with at 2.5 mg/mL or greater (P < .03). Cell clonogenicity was not significantly different between saline, culture medium, or 0.5 mg/mL SFB. Clonogenicity was lower with all tested LEB concentrations compared with saline or medium (P < .02). Conclusion: In vitro toxicity of SFB on canine chondrocytes is concentration dependent. Liposomal encapsulated bupivacaine may have time-dependent effects resulting in chondrotoxicity. Clinical significance: Clinically relevant concentrations of SFB after a single injection may not result in chondrotoxic effects in vitro. Liposomal encapsulated bupivacaine should not be used in the articular environment.

show abstract

Section: Discussionsupporting

confidence: 60%

Effect of bupivacaine concentration and formulation on canine chondrocyte viability in vitro

2021

View full text Add to dashboard Cite

show abstract

“…Data were analyzed using commercial software. 5 T0 concentrations were corrected to account for the inherent dilution created by infusion of either bupivacaine or saline into the joint using the following formula (T0c): where initial volume (Vi) equals 0.08 mL/kg [ 7 ] and final volume (Vf) equals (Vi − Vaspirated) + Vtreatment.…”

Section: Main Textmentioning

confidence: 99%

“…As a result, following aspiration at T0 and the subsequent infusion of the treatment volume (~ 2.5 mL), later PGE 2 concentrations would be decreased due to dilution by the larger relative fluid volume. In a previous study evaluating how quickly bupivacaine elutes from the stifle following intra-articular administration, a similar dilutional effect was noted following treatment injection, and our pre-injection fluid volume approximation was calculated based on those methods [ 7 ]. Therefore, 0.08 mL/kg synovial fluid volume was approximated for each stifle and defined as Vi [ 7 ].…”

Section: Main Textmentioning

confidence: 99%

“…A time- and dose-dependent effect of bupivacaine on chondrotoxicity in vitro is reported [ 1 , 4 , 14 – 16 ]; however, to our knowledge, chondrolysis has not been reported in the veterinary literature following a single intra-articular dose of bupivacaine in vivo. A pharmacologic study of a single intra-articular dose of bupivacaine identified a rapid decrease in bupivacaine concentrations (11–25% of baseline bupivacaine concentration) 30 min after injection in dogs [ 7 ]. Given the rapid clearance of a single intra-articular dose of bupivacaine and the results of our study, a single injection of bupivacaine is unlikely to cause sufficient synovitis to be the sole cause of chondrolysis.…”

Section: Main Textmentioning

confidence: 99%

See 1 more Smart Citation

Effect of a single intra-articular injection of bupivacaine on synovial fluid prostaglandin E2 concentrations in normal canine stifles

et al. 2018

View full text Add to dashboard Cite

ObjectiveTo identify if synovial fluid prostaglandin E2 increases in response to a single intra-articular dose of bupivacaine in the normal canine stifle.ResultsThere were no significant differences in synovial fluid prostaglandin E2 (PGE2) concentrations between treatment groups or over time within bupivacaine or saline groups. Samples requiring ≥ 3 arthrocentesis attempts had significantly higher PGE2 concentrations compared to samples requiring 1 or 2 attempts. Following correction for number of arthrocentesis attempts, PGE2 concentrations were significantly higher than baseline at 24 and 48 h in the bupivacaine group; however there were no significant differences between the bupivacaine and saline groups. In normal dogs, a single bupivacaine injection did not cause significant synovial inflammation, as measured by PGE2 concentrations, compared to saline controls. Future research should minimize aspiration attempts and include evaluation of the synovial response to bupivacaine in clinical cases with joint disease.

show abstract

“…Commonly used local anesthetics include lidocaine, bupivacaine, ropivacaine, and procaine [6]. Local anesthetic injection is associated with rapid onset of analgesia; however, rapid absorption, distribution, and clearance from the injection site result in a short duration of pain relief (~ 4 h) thereby limiting the use of local anesthetics in the management of chronic OA pain [6, 10–14]. The addition of a vasoconstrictor, such as epinephrine, can increase the duration of local anesthesia, but is contraindicated for use in IA injections [6, 15].…”

Section: Introductionmentioning

confidence: 99%

Physical and Chemical Compatibility of Extended-Release Triamcinolone Acetonide (TA-ER) with Common Local Anesthetics

et al. 2019

View full text Add to dashboard Cite

IntroductionIntra-articular (IA) corticosteroids are used extensively for the treatment of patients with knee osteoarthritis pain. In clinical practice, local anesthetics are frequently combined with corticosteroids prior to IA injection to provide rapid-onset analgesia. From this common practice there is no evidence to suggest that the addition of local anesthetics to corticosteroid preparations, including triamcinolone acetonide (TA), alters the physical properties or efficacy of the corticosteroid. Triamcinolone acetonide extended-release (TA-ER, formerly FX006) is a novel, microsphere-based TA formulation that demonstrated analgesic efficacy in phase 2 and 3 randomized controlled trials.MethodsThe current study assessed the compatibility of TA-ER and lidocaine, ropivacaine, and/or bupivacaine in vitro. The TA-ER and local anesthetic mixtures were assayed for changes in syringeability, pH, particle size, percentage free drug, purity, and appearance compared with TA-ER alone.ResultsBy these measures, the combination of local anesthetics with TA-ER did not negatively impact the chemical or physical properties of TA-ER when compared to TA-ER controls.ConclusionThese results demonstrate that lidocaine, bupivacaine, and ropivacaine are physically and chemically compatible with TA-ER, suggesting that local anesthetic solutions can be added to TA-ER preparations in clinical practice without adversely affecting TA-ER in vitro product characteristics.FundingFlexion Therapeutics, Inc.

show abstract

Synovial fluid bupivacaine concentrations following single intra‐articular injection in normal and osteoarthritic canine stifles

Cited by 11 publications

References 18 publications

Effect of bupivacaine concentration and formulation on canine chondrocyte viability in vitro

Effect of bupivacaine concentration and formulation on canine chondrocyte viability in vitro

Effect of a single intra-articular injection of bupivacaine on synovial fluid prostaglandin E2 concentrations in normal canine stifles

Physical and Chemical Compatibility of Extended-Release Triamcinolone Acetonide (TA-ER) with Common Local Anesthetics

Contact Info

Product

Resources

About