Effect of midazolam pretreatment on the intravenous toxicity of lidocaine with and without epinephrine in rats.

The effect of the benzodiazepine midazolam on the intravenous toxicity of lidocaine with and without epinephrine was studied in male Sprague-Dawley rats. Test rats with and control rats without midazolam premedication (2.5 mg/kg intraperitoneally, 10% of the median dose that caused loss of the righting reflex in a third group of rats) were given 2% lidocaine with and without 10 micrograms/ml epinephrine intravenously in doses sufficient to construct log-dose response curves for both convulsant and lethal responses. In control rats the median convulsant dose (CD50) of lidocaine was 15.2 mg/kg given alone and 10.9 mg/kg with epinephrine (a statistically significant difference); respective values for the median lethal dose (LD50) were 26.4 and 18.5 mg/kg (also statistically significant). While epinephrine enhanced lidocaine seizure activity and lethality by approximately 50%, midazolam almost completely prevented lidocaine-induced convulsions but had no significant effect on mortality.