Lidocaine and bupivacaine cardiorespiratory toxicity is additive: a study in rats

The purpose of this study was to determine whether equipotent solutions of lidocaine, bupivacaine, or a mixture of these compounds infused at a fixed rate in anesthetized rats resulted in equivalent lethal cardiorespiratory toxicity and to establish whether the lethality of the individual drugs was additive. This was assessed by comparing the time to respiratory and circulatory arrest, determining the lethal doses of administered local anesthetic in each group, and ascertaining the concentration of lidocaine or bupivacaine, or both, at the time of circulatory arrest. The times to respiratory and circulatory arrest were similar in rats receiving either lidocaine (2%) or bupivacaine (0.5%) or a mixture of 1% lidocaine and 0.25% bupivacaine. The mean lidocaine-to-bupivacaine cumulative lethal dose ratio (3.36) and concentration ratio (2.33) were determined and used to calculate lidocaine equivalent values for bupivacaine data. Lidocaine equivalent cumulative lethal doses and plasma concentrations were similar in all three groups studied. This work suggests that the lethal cardiorespiratory toxicity of lidocaine and bupivacaine associated with intravenous infusion is additively toxic in rats.