Tetrodotoxin-Bupivacaine-Epinephrine Combinations for Prolonged Local Anesthesia

Marine Drugs

Charles B. Berde²  Umeshkumar Athiraman²  Barak Yahalom²  David Zurakowski²  Gabriel Corfas¹ 

[1] Departments of Otolaryngology and Neuroscience, Children’s Hospital Boston, Harvard Medical School, 300 Longwood Avenue, Boston, MA 02115, USA;Department of Anesthesiology, Perioperative and Pain Medicine, Children’s Hospital Boston, Harvard Medical School, 300 Longwood Avenue, Boston, MA 02115, USA;

关键词: tetrodotoxin;    bupivacaine;    epinephrine;    local anesthesia;    sciatic blockade;   

DOI  :  10.3390/md9122717

来源: mdpi

【 摘 要 】

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.

【 授权许可】

CC BY   
© 2011 by the authors; licensee MDPI, Basel, Switzerland.