Propofol Prevents or Elevates the Threshold for Lidocaine-Induced Seizures in Rats

Hypothesizing that propofol's pro and anticonvulsant effects might be dose dependent, we determined the effect of 25, 50, and 100% of a previously determined anesthetic dose of propofol for rats on the amount of lidocaine required to induce seizures. Lidocaine was infused at 2.5 mg kg-1 min-1 into animals that were receiving either (a) 70% N2O balance O2 (n = 10), control group, (b) 2 mg kg-1 bolus followed by 12 mg kg-1 h-1 propofol infusion with 70% N2O (n = 10), group 2, (c) 4 mg kg-1 followed by 24 mg kg-1 h-1 propofol with 70% N2O (n = 20), group 3, (d) 8 mg kg-1 followed by 48 mg kg-1 h-1 propofol with 70% N2O (n = 10), group 4, or (e) 8 mg kg-1 followed by 48 mg kg-1 h-1 propofol without N2O (n = 10), group 5. Temperature PaCO2, and pH were maintained within normal limits until disturbed by seizure activity or lidocaine toxicity. The plasma concentration of lidocaine required to induce electroencephalographically (EEG) detected seizures was 8.7 ± 0.7 μg ml-1 in control animals, 16 ± 1.7 μg ml-1 in group 2, and 32 ± 4 μg ml-1 in 13 animals from group 3 that experienced a seizure (p < 0.01). Seizures did not occur in seven of 20 group 3 rats. These animals died from lidocaine toxicity or the experiment was terminated at a level of toxicity (225 mg kg-1) that had induced an isoelectric EEG for up to 1 h and precluded maintenance of viable blood pressure, pH, PaCO2, etc. All rats that received an anesthetic dose of propofol, with or without N2O, died from lidocaine toxicity or were killed at 225 mg kg-1 without having experienced a seizure. Contrary to our hypothesis, we found no evidence for a proconvulsant effect of propofol within the dose range examined. Instead, our results indicate that anesthetic doses of propofol prevent, and subanesthetic doses prevent or elevate the threshold for, lidocaine-induced seizures in this experimental setting.