Torbiner M L, Yagiela J A, Mito R S
Section of Oral Biology, UCLA School of Dentistry 90024.
Anesth Analg. 1989 Jun;68(6):744-9.
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.
在雄性斯普拉格 - 道利大鼠中研究了苯二氮䓬类药物咪达唑仑对含肾上腺素和不含肾上腺素的利多卡因静脉毒性的影响。对预先给予咪达唑仑（2.5毫克/千克腹腔注射，为使第三组大鼠翻正反射消失的半数有效剂量的10%）的试验大鼠和未预先给予咪达唑仑的对照大鼠静脉注射含10微克/毫升肾上腺素和不含肾上腺素的2%利多卡因，剂量足以构建惊厥反应和致死反应的对数剂量反应曲线。在对照大鼠中，单独给予利多卡因时的半数惊厥剂量（CD50）为15.2毫克/千克，与肾上腺素合用时为10.9毫克/千克（有统计学显著差异）；半数致死剂量（LD50）的相应值分别为26.4和18.5毫克/千克（也有统计学显著差异）。虽然肾上腺素使利多卡因的惊厥活性和致死率提高了约50%，但咪达唑仑几乎完全预防了利多卡因引起的惊厥，但对死亡率无显著影响。
