Tetrodotoxin-Bupivacaine-Epinephrine Combinations for Prolonged Local Anesthesia
AbstractCurrently 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.
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Berde, C.B.; Athiraman, U.; Yahalom, B.; Zurakowski, D.; Corfas, G.; Bognet, C. Tetrodotoxin-Bupivacaine-Epinephrine Combinations for Prolonged Local Anesthesia. Mar. Drugs 2011, 9, 2717-2728.
Berde CB, Athiraman U, Yahalom B, Zurakowski D, Corfas G, Bognet C. Tetrodotoxin-Bupivacaine-Epinephrine Combinations for Prolonged Local Anesthesia. Marine Drugs. 2011; 9(12):2717-2728.Chicago/Turabian Style
Berde, Charles B.; Athiraman, Umeshkumar; Yahalom, Barak; Zurakowski, David; Corfas, Gabriel; Bognet, Christina. 2011. "Tetrodotoxin-Bupivacaine-Epinephrine Combinations for Prolonged Local Anesthesia." Mar. Drugs 9, no. 12: 2717-2728.