Abstract
Increased plasma concentration of local anesthetics induces central nervous system (CNS) and cardiovascular toxicity, and inhibition of GABAergic inhibitory neurons are involved in this toxicity. An increase in the concentration of local anesthetics in the whole brain is required for inducing CNS toxicity since GABAergic inhibitory neurons are extensively distributed in the brain, and it is not induced by injecting local anesthetics to restricted areas in the brain. General anesthesia inhibits local anesthetic-induced CNS toxicity. Among commonly used agents during anesthesia, sympathetic α2-adrenergic receptor agonists such as dexmedetomidine, and β1-adrenergic receptor antagonists such as propranolol increase the threshold plasma concentration for inducing convulsions as well as the dose of local anesthetics for inducing convulsions. These agents increase the concentration of local anesthetics in the brain at the onset of convulsions, suggesting that they did not affect the diffusion of local anesthetics from the blood vessels to the extracellular fluid in the brain. Regarding concentrations of local anesthetics measured by microdialysis using the retrograde calibration technique, the diffusion ratio of levobupivacaine to the extracellular fluid in the brain is much lower than that of lidocaine during intravenous infusion.
