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Mar. Drugs 2011, 9(12), 2717-2728; doi:10.3390/md9122717

Tetrodotoxin-Bupivacaine-Epinephrine Combinations for Prolonged Local Anesthesia

1
Department of Anesthesiology, Perioperative and Pain Medicine, Children’s Hospital Boston, Harvard Medical School, 300 Longwood Avenue, Boston, MA 02115, USA
2
Departments of Otolaryngology and Neuroscience, Children’s Hospital Boston, Harvard Medical School, 300 Longwood Avenue, Boston, MA 02115, USA
*
Author to whom correspondence should be addressed.
Received: 9 October 2011 / Revised: 18 November 2011 / Accepted: 21 November 2011 / Published: 15 December 2011
(This article belongs to the Special Issue Tetrodotoxin)
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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. View Full-Text
Keywords: tetrodotoxin; bupivacaine; epinephrine; local anesthesia; sciatic blockade tetrodotoxin; bupivacaine; epinephrine; local anesthesia; sciatic blockade
This is an open access article distributed under the Creative Commons Attribution License (CC BY 3.0).

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MDPI and ACS Style

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.

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