The Cardiotoxicity of Local Anesthetics: The Place of Ropivacaine

Central and regional block procedures have a well-defined role as safe and effective methods in modern anesthesia and analgesia with long-acting local anesthetics. Recent studies have shown that the incidence of intoxication by these drugs is a rare but catastrophic event. As classic neuronal sodium channel inhibitors, local anesthetics block peripheral fast voltage-gated sodium channels on neuronal axons, and these drugs have a particularly high level of activity in the CNS and the cardiovascular system. CNS-toxicity follows a two-stage process, whereby at lower concentrations inhibitory neurons are blocked first resulting in generalized convulsions, and at higher concentrations a global CNS depression can be seen. Although seizures are an impressive clinical syndrome, they can often be treated safely without permanent damage. More important is the cardiotoxicity of these drugs, which can be divided into indirect cerebrally mediated and a direct myocardial component. Like CNS-toxicity in general, indirect cardiotoxicity demonstrates an initial stimulating effect, followed by a depressive component at higher concentrations. Direct myocardial actions are comprised of negative chronotropic, dromotropic and inotropic effects. For dromotropy, stereoselectivity was found. The S-(-)-isomers of the longacting local anesthetics were less delayed compared to racemic mixtures and the R-(+)-enantiomers. For inotropy, no stereospecific depression of this parameter was noted between isomers of ropivacaine or bupivacaine, but bupivacaine produced a significantly greater depression of LV pressure than ropivacaine, mepivacaine, or lidocaine. Pharmacokinetic differences in lipophilicity of local anesthetics correlate well with the depression mitochondrial ATP-synthesis in fast metabolizing cells. Intracellular ATP-level may be involved in contractility and resuscitation of cardiomyocytes, as be proven by in-vitro and in-vivo data. Therefore the use of pure optical S-(-)-isomers of local anesthetics may help to reduce these rare but catastrophic events. Presently, ropivacaine appears to be the safest long-acting local anesthetic.