Effects of simultaneous administration of local anesthetics on seizure induced threshold: an experimental study in...

The effect of the simultaneous administration of local anesthetics, whether synergistic, additive, or antagonistic, has not yet been established. This study investigated the interaction between concurrently administered short- and long-acting local anesthetics.

A total of 160 male Sprague-Dawley rats were divided into 16 groups (n = 10 each): 4 local anesthetic alone groups (lidocaine, mepivacaine, ropivacaine, and levobupivacaine) and 12 simultaneous administration groups that received adjusted concentrations of short- and long-acting local anesthetics. Local anesthetics were administered at a constant rate until seizure onset, which was determined by electroencephalographic monitoring. The cumulative dose required to induce seizures was calculated in each group. A linear regression analysis was performed to assess the relationship between the doses of the combined agents, with additivity inferred from an adjusted R² of > 0.7. In addition, pharmacodynamic interactions were evaluated using an interaction index based on the Loewe additivity model.

For all combinations of local anesthetics, R² was > 0.7. A linear regression analysis indicated an additive effect for each combination. Furthermore, an analysis of the interaction index indicated a tendency toward additivity.

This study revealed no clear evidence of antagonism or synergism for the simultaneous administration of short-acting (lidocaine or mepivacaine) and long-acting anesthetics (ropivacaine or levobupivacaine). An additive effect was suggested in terms of the seizure threshold when short- and long-acting local anesthetics were administered simultaneously. This finding may therefore support the safe and effective combined use of local anesthetics in clinical regional anesthesia.