Local anaesthesia efficacy: discrepancies between in vitro and in vivo studies

Electrophysiological studies on isolated nerves have been used extensively in the past to assess the comparative efficiency of local anaesthetics as agents of peripheral nerve blockade. It is shown here that three closely related amide local anaesthetics behave differently in vitro and in vivo. In terms of onset of action and of maximum suppression of the evoked action potential, mepivacaine proved a less efficient anaesthetic than lidocaine or prilocaine on isolated nerves, but in parallel studies on the sciatic nerve of live animals and in the absence of vasoconstrictors: (a) mepivacaine's potency was superior to that of the other two agents, (b) its speed of onset of anaesthetic action was at least as good and (c) its duration of action was found to be considerably longer. These results, in combination with the physical properties of the anaesthetics examined, favour differential ionization as the cause of the reduced performance of mepivacaine in the nerve bath. Thus, studies on isolated nerves, which are often quoted in the pharmacological literature, can be poor guides to the in vivo comparative efficacy of local anaesthetics.