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  • Duration and Local Toxicity of Sciatic Nerve Blockade With Coinjected Site 1 Sodium-Channel Blockers and Quaternary Lidocaine Derivatives

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ORIGINAL ARTICLES
Duration and Local Toxicity of Sciatic Nerve Blockade With Coinjected Site 1 Sodium-Channel Blockers and Quaternary Lidocaine Derivatives
  1. Sahadev A. Shankarappa, MBBS, MPH, PhD*,†,
  2. Itay Sagie, BS*,
  3. Jonathan H. Tsui, MEng*,†,
  4. Homer H. Chiang, MS*,†,
  5. Cristina Stefanescu, BS*,†,
  6. David Zurakowski, PhD* and
  7. Daniel S. Kohane, MD, PhD*,†
  1. From the *Department of Anesthesiology, Perioperative and Pain medicine, Children’s Hospital Boston, Harvard Medical School, Boston; and
  2. †Koch Institute of Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA.
  1. Address correspondence to: Daniel S. Kohane, MD, PhD, Department of Anesthesiology and Perioperative Medicine, Boston Children’s Hospital, 300 Longwood Ave., Boston, MA 02114 (e-mail: Daniel.kohane{at}childrens.harvard.edu).

Abstract

Background and Objectives Quaternary lidocaine derivatives (QLDs) have recently received much attention because of their potential application in prolonged or sensory-selective local anesthesia. However, associated tissue toxicity is an impeding factor that makes QLDs unfavorable for clinical use. Based on the proposed intracellular site of action, we hypothesized that nerve blocks obtained from lower concentrations of QLDs would be enhanced by the coapplication of extracellularly acting site 1 sodium-channel blocker, resulting in prolonged block duration but with minimal tissue toxicity.

Methods Quaternary lidocaine derivatives (QX-314 or QX-222), site 1 sodium-channel blockers (tetrodotoxin [30 μM] or saxitoxin [12.5 μM]), or both were injected in the vicinity of the sciatic nerve. Thermal nociceptive block was assessed using a modified hot plate test; motor block by a weight-bearing test. Tissue from the site of injection was harvested for histological assessment.

Results Coapplication of 25 mM QX-314 or 100 mM QX-222 with site 1 sodium-channel blockers produced an 8- to 10- fold increase in the duration of nerve blocks (P < 0.05), compared with QLDs or site 1 blockers alone. Quaternary lidocaine derivatives elicited severe myotoxicity; this was not exacerbated by coinjection of the site 1 sodium-channel blockers.

Conclusions Coadministration of site 1 sodium-channel blockers and QLDs greatly prolongs the duration of peripheral nerve block without enhancing local tissue injury, but minimal myotoxicity still persists. It is not clear that the risks of QLDs are outweighed by the benefits in providing prolonged nerve blockade.

https://doi.org/10.1097/AAP.0b013e31826125b3

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    Footnotes

    • S.A.S. and I.S. are co–first authors on this manuscript and contributed equally to this work.

    • Author contributions: S.A.S., I.S. and D.S.K. designed study, analyzed data, and wrote the manuscript. S.A.S. and I.S. have equal contribution. S.S., I.S., J.H.T., H.H.C., and C.S. performed animal experiments and histological grading. D.Z. performed the statistical analysis.