Neurotoxicity of adjuvants used in perineural anesthesia and analgesia in comparison with ropivacaine.
| Autor: | Williams BA; University of Pittsburgh School of Medicine, Department of Anesthesiology, Pittsburgh, PA, USA. williamsba@anes.upmc.edu, Hough KA, Tsui BY, Ibinson JW, Gold MS, Gebhart GF |
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| Jazyk: | angličtina |
| Zdroj: | Regional anesthesia and pain medicine [Reg Anesth Pain Med] 2011 May-Jun; Vol. 36 (3), pp. 225-30. |
| DOI: | 10.1097/AAP.0b013e3182176f70 |
| Abstrakt: | Background and Objectives: Clonidine, buprenorphine, dexamethasone, and midazolam (C, B, D, M) have been used to prolong perineural local anesthesia in the absence of data on the influence of these adjuvants on local anesthetic-induced neurotoxicity. Therefore, the impact of these adjuvants on ropivacaine (R)-induced death of isolated sensory neurons was assessed. Methods: The trypan blue exclusion assay was used to assess death of sensory neurons isolated from adult male Sprague-Dawley rats. Drugs were applied, alone or in combination, for 2 or 24 hrs at 37°C. Results: Neuronal viability was halved by 24-hr exposure to R (2.5 mg/mL), far exceeding the neurotoxicity of C, B, D, or M (at 2-100 times estimated clinical concentrations). Plain M at twice the estimated clinical concentration produced a small but significant increase in neurotoxicity at 24 hrs. After 2-hr exposure, high concentrations of B, C, and M increased the neurotoxicity of R; the combination of R + M killed more than 90% of neurons. Estimated clinical concentrations of C + B (plus 66 μg/mL D) had no influence on (i) R-induced neurotoxicity, (ii) the increased neurotoxicity associated with the combination of R + M, or (iii) the neurotoxicity associated with estimated clinical concentrations of M. There was increased neurotoxicity with 133 μg/mL D combined with R + C + B. Conclusions: Results with R reaffirm the need to identify ways to mitigate local anesthetic-induced neurotoxicity. While having no protective effect on R-induced neurotoxicity in vitro, future research with adjuvants should address if the C + B + D combination can enable reducing R concentrations needed to achieve equianalgesia (and/or provide equal or superior duration, in preclinical in vivo models). |
| Databáze: | MEDLINE |
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