Tetrodotoxin-Bupivacaine-Epinephrine Combinations for Prolonged Local Anesthesia

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

On the coupling of local 3D solutions and global 2D shell theory in structural mechanics

Most of mechanical systems and complex structures exhibit plate and shell components. Therefore, 2D simulation, based on plate and shell theory, appears as an appealing choice in structural analysis as it allows reducing the computational complexity. Nevertheless, this 2D framework fails for capturing rich physics compromising the usual hypotheses considered when deriving standard plate and shell theories. To circumvent, or at least alleviate this issue, authors proposed in their former works an in-plane-out-of-plane separated representation able to capture rich 3D behaviors while keeping the computational complexity of 2D simulations. However, that procedure it was revealed to be too intrusive for being introduced into existing commercial softwares. Moreover, experience indicated that such enriched descriptions are only compulsory locally, in some regions or structure components. In the present paper we propose an enrichment procedure able to address 3D local behaviors, preserving the direct minimally-invasive coupling with existing plate and shell discretizations. The proposed strategy will be extended to inelastic behaviors and structural dynamics