Benzodiazepines protect mice from local anesthetic convulsions and deaths

Median convulsant (CD50) and median lethal (LD50) doses of intraperitoneal lidocaine, bupivacaine, and etidocaine were determined in 149 mice. Another 496 mice were pretreated with intramuscular diazepam, lorazepam, or midazolam, 1 mg/kg. Fifteen minutes later, lidocaine, bupivacaine, or etidocaine was given intraperitoneally and the incidence of convulsions and deaths recorded. Benzodiazepines significantly reduced the incidence or convulsions. For instance, etidocaine, 54.9 mg/kg, produced 50% convulsions in untreated mice compared to 6.9%, 3.4%, and 3.4% after diazepam, lorazepam, or midazolam, respectively. Benzodiazepines also enhanced survival, as shown by significant increases in the LD50s. The bupivacaine LD50, for example, increased from 58.7 mg/kg in untreated mice to 75.2, 79.1, and 83.6 mg/kg after diazepam, lorazepam, or midazolam, respectively. Similarly, bupivacaine, 58.7 mg/kg, killed 50% of untreated mice, but only 1.2%, 9.7%, and 4.5% of mice treated with diazepam, lorazepam, or midazolam, respectively. It is concluded that premedication with a benzodiazepine significantly reduces the incidence of convulsions in mice and lowers the mortality rate as well. In equal intramuscular doses, midazolam proved to be the most effective anticonvulsant and diazepam the least. Etidocaine and bupivacaine convulsions were more difficult to suppress than those induced by lidocaine. On the other hand, the lethality of lidocaine was least reduced by these benzodiazepines.