What local anesthetic agents were developed as a result of bupivacaine toxicity?

Updated: Jan 09, 2019
  • Author: Raffi Kapitanyan, MD; Chief Editor: David Vearrier, MD, MPH  more...
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The occurrence of numerous fatalities associated with the cardiovascular toxicity of bupivacaine prompted a search for less toxic long-acting local anesthetic agents. This search resulted in the development of levobupivacaine and ropivacaine.

Bupivacaine is a 50:50 racemic mixture of a dextrorotatory R-(+)-enantiomer and a levorotatory S-(-)-enantiomer. Clinical studies demonstrated that the S-(-)-enantiomer, levobupivacaine, has less potential for CNS and cardiovascular toxicity. In particular, the intravascular dose required to cause lethality is almost 78% greater for levobupivacaine compared with the R-(+) enantiomer.

Further clinical trials in the 1990s led to the introduction in 1996 of ropivacaine, a pure S-(-) enantiomer. Ropivacaine, like bupivacaine, has the capacity to produce differential blockade but has a better sensorimotor dissociation at lower doses. This long-acting amide is the first local anesthetic drug developed with initial extensive toxicological studies before its clinical release. Although ropivacaine may be associated with acute CNS and cardiovascular toxicity, the incidence appears to be extremely low.

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