Mixtures of local anesthetics are no more toxic than the parent drugs

Mixtures of local anesthetics can combine the best features of both components. The authors assayed the systemic toxicity of local anesthetic mixtures given subcutaneously to mice. Convulsions regularly preceded death. The median convulsant dose (CD50) of bupivacaine was one-fourth that of lidocaine, and one-seventh that of chloroprocaine. The median lethal dose (LD50) of chloroprocaine was twice the CD50, whereas the LD50 of bupivacaine was but little greater than the CD50. Hence, the more potent the agent, the greater is the chance of death from a convulsant dose of local anesthetic. Conversion to lidocaine-equivalent doses permitted comparisons between mixtures. None of the mixtures were more convulsant or more lethal than their parent components; lidocaine-containing mixtures were significantly less lethal than the lidocaine norm. Mixing increased the distance between convulsant and lethal doses, with survival from convulsions induced by bupivacaine-containing mixtures enhanced in particular. It is concluded that local anesthetic toxicity is essentially additive.