Discrepancy between the development of tolerance to bupivacaine in extradural and spinal anaesthesia in rabbits

We gave equal groups of rabbits seven extradural (500 micrograms kg-1) or intrathecal (250 micrograms kg-1) injections of bupivacaine, at 24-h intervals. A decrease in the duration of motor block was observed after the extradural injections. The intrathecal injections exerted a reproducible effect. An additional regimen was tested in which five doses of bupivacaine 125 micrograms kg-1 were administered intrathecally after a loading dose of 250 micrograms kg-1, when the animals showed partial recovery from the previous dose; there was no decrease in the effect. The absence of tolerance to intrathecal bupivacaine implies that tachyphylaxis to extradural local anaesthetics results from a decrease in availability of the drug to the neural target, rather than a diminution in effect at the site of action.