[Are combinations of local anesthetics dangerous?]

Although local anaesthetic mixtures are often used, there is often no scientific basis for this. Interactions between the local anaesthetics in the mixture can even increase their toxicity. Such interactions may be due to the physical chemical properties of each constituent (this is not a real problem for amide local anaesthetics), to a mutual displacement from the binding sites on the plasma proteins or to an additional effect on membrane receptors. This displacement would seem to benefit the least toxic drug: the toxicity of local anaesthetic mixtures may therefore be reduced; for example, lidocaine and mepivacaine are displaced by bupivacaine. Moreover, the fraction of drug which leaves the blood vessel is greater than the serum free fraction. During chronic administration, neurological toxicity and free fraction are narrowly linked. When using local anaesthetic mixtures, it must be remembered that potency and toxicity of a local anaesthetic are closely correlated and that the toxic effects are, at least, additive.