IRREVERSIBLE CONDUCTION BLOCK IN ISOLATED NERVE BY HIGH-CONCENTRATIONS OF LOCAL-ANESTHETICS

Background: Delivery of large doses of local anesthetics for spinal an esthesia by repeated injections or continuous infusion could expose th e cauda equina to concentrations of drug that may be neurotoxic per se . We studied this possible neurotoxic effect by assessing recovery fro m conduction blockade of desheathed peripheral nerves after exposure t o some of the local anesthetic solutions commonly used for spinal anes thesia. Methods: The reversibility of conduction blockade was studied in desheathed bullfrog sciatic nerves, using the sucrose-gap method fo r recording compound action potentials, before and during exposure to local anesthetics and during drug washout. The nerves were exposed for 15 min to 5% or 1.5% lidocaine, with or without 7.5% dextrose; 0.5% t etracaine; or 0.75% bupivacaine (the latter two without dextrose). Som e nerves were also bathed in 7.5% dextrose (without local anesthetic) or in 0.06% tetracaine, which in this preparation is equipotent to 5% lidocaine. After 15 min in the drug, the nerves were washed for 2-3 h and soaked in Ringer's solution overnight. Nerves exposed only to Ring er's solution served as controls. We also studied neuronal uptake and washout of radiolabeled lidocaine. Results: Exposure of nerves to 5% l idocaine, with or without 7.5% dextrose, or to 0.5% tetracaine resulte d in irreversible total conduction blockade, whereas 1.5% lidocaine or 0.75% bupivacaine caused 25-50% residual block after the 2-3-h wash. Nerves exposed to Ringer's solution, 7.5% dextrose or 0.06% tetracaine had 0-10% residual block after 2-3 h wash. The action potential of al l nerves declined after overnight soak to between 30-60% of the contro l value, except for those nerves exposed to 5% lidocaine or 0.5% tetra caine, which showed no activity. Exposure to 5% lidocaine for periods of only 4-5 min produced total, irreversible loss of conduction. The u ptake by and washout of radiolabeled lidocaine from the nerves indicat e that the maximum amount of residual drug after 2-4 min of exposure t o 5% lidocaine and a 3-h wash should cause at most only 50% conduction block. Conclusions: Solutions of 5% lidocaine and 0.5% tetracaine tha t have been associated with clinical eases of cauda equina syndrome af ter continuous spinal anesthesia caused irreversible conduction block in desheathed amphibian nerve. Whether these in vitro actions also occ ur in mammalian nerves in vivo is an important, clinically relevant qu estion now under investigation in our laboratory.