Tetrodotoxin-Bupivacaine-Epinephrine Combinations for Prolonged Local Anesthesia

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Tetrodotoxin-Bupivacaine-Epinephrine Combinations for Prolonged Local Anesthesia

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Title: Tetrodotoxin-Bupivacaine-Epinephrine Combinations for Prolonged Local Anesthesia
Author: Athiraman, Umeshkumar; Bognet, Christina; Berde, Charles Benjamin; Yahalom, Barak; Zurakowski, David; Corfas, Gabriel

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Citation: Berde, Charles B., Umeshkumar Athiraman, Barak Yahalom, David Zurakowski, Gabriel Corfas, and Christina Bognet. 2011. Tetrodotoxin-Bupivacaine-Epinephrine combinations for prolonged local anesthesia. Marine Drugs 9(12): 2717-2728.
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Abstract: Currently available local anesthetics have analgesic durations in humans generally less than 12 hours. Prolonged-duration local anesthetics will be useful for postoperative analgesia. Previous studies showed that in rats, combinations of tetrodotoxin (TTX) with bupivacaine had supra-additive effects on sciatic block durations. In those studies, epinephrine combined with TTX prolonged blocks more than 10-fold, while reducing systemic toxicity. TTX, formulated as Tectin, is in phase III clinical trials as an injectable systemic analgesic for chronic cancer pain. Here, we examine dose-duration relationships and sciatic nerve histology following local nerve blocks with combinations of Tectin with bupivacaine 0.25% (2.5 mg/mL) solutions, with or without epinephrine 5 µg/mL (1:200,000) in rats. Percutaneous sciatic blockade was performed in Sprague-Dawley rats, and intensity and duration of sensory blockade was tested blindly with different Tectin-bupivacaine-epinephrine combinations. Between-group comparisons were analyzed using ANOVA and post-hoc Sidak tests. Nerves were examined blindly for signs of injury. Blocks containing bupivacaine 0.25% with Tectin 10 µM and epinephrine 5 µg/mL were prolonged by roughly 3-fold compared to blocks with bupivacaine 0.25% plain (P < 0.001) or bupivacaine 0.25% with epinephrine 5 µg/mL (P < 0.001). Nerve histology was benign for all groups. Combinations of Tectin in bupivacaine 0.25% with epinephrine 5 µg/mL appear promising for prolonged duration of local anesthesia.
Published Version: doi:10.3390/md9122717
Other Sources: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3280572/pdf/
Terms of Use: This article is made available under the terms and conditions applicable to Other Posted Material, as set forth at http://nrs.harvard.edu/urn-3:HUL.InstRepos:dash.current.terms-of-use#LAA
Citable link to this page: http://nrs.harvard.edu/urn-3:HUL.InstRepos:8617188

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