Electroencephalographic effects of laudanosine in an animal model of epilepsy

We examined the effects of laudanosine, one of the principal metabolites of atracurium. on the electroencephalogram (EEG) in an animal model of induced epilepsy. Fourteen rabbits were anaesthetized with 4% halothane in oxygen, the trachea intubated and the lungs ventilated mechanically with 30% oxygen and 1% halothane in nitrogen. Animals were assigned randomly to receive either an in fusion of laudanosine (laudanosine group, n = 7) at a rate calculated to produce plasma concentrations similar to those found following the clinical use of atracurium, or an equal volume of normal saline (control group, n = 7). To induce an epileptogenic focus, gel-foam sponges soaked in a pH-adjusted 4% cefazolin solution were applied bilaterally to the parietal cortical surface. This resulted in the production of spike and burst EEG activity in all animals. However, scoring the frequency of the spikes and bursts revealed no significant differences between the laudanosine and control groups. We conclude that, in this animal model of epilepsy, no increased incidence of seizure activity was produced by mean plasma laudanosine concentrations as great as 0.8 μg ml^-1. These results suggest that the routine use of atracurium is unlikely to provoke seizures, even in the presence of an epileptogenic focus.