de Jong R H, Bonin J D
Anesthesiology. 1981 Mar;54(3):177-81. doi: 10.1097/00000542-198103000-00001.
Mixtures of local anesthetics can combine the best features of both components. The authors assayed the systemic toxicity of local anesthetic mixtures given subcutaneously to mice. Convulsions regularly preceded death. The median convulsant dose (CD50) of bupivacaine was one-fourth that of lidocaine, and one-seventh that of chloroprocaine. The median lethal dose (LD50) of chloroprocaine was twice the CD50, whereas the LD50 of bupivacaine was but little greater than the CD50. Hence, the more potent the agent, the greater is the chance of death from a convulsant dose of local anesthetic. Conversion to lidocaine-equivalent doses permitted comparisons between mixtures. None of the mixtures were more convulsant or more lethal than their parent components; lidocaine-containing mixtures were significantly less lethal than the lidocaine norm. Mixing increased the distance between convulsant and lethal doses, with survival from convulsions induced by bupivacaine-containing mixtures enhanced in particular. It is concluded that local anesthetic toxicity is essentially additive.
局部麻醉药的混合制剂可兼具两种成分的最佳特性。作者测定了皮下给予小鼠局部麻醉药混合制剂后的全身毒性。惊厥通常先于死亡出现。布比卡因的半数惊厥剂量（CD50）是利多卡因的四分之一，是氯普鲁卡因的七分之一。氯普鲁卡因的半数致死剂量（LD50）是CD50的两倍，而布比卡因的LD50仅略高于CD50。因此，药物的效力越强，因惊厥剂量的局部麻醉药而死亡的可能性就越大。换算成等效利多卡因剂量便于比较混合制剂。没有一种混合制剂比其母体成分更易引发惊厥或更具致死性；含利多卡因的混合制剂的致死性明显低于利多卡因标准制剂。混合增加了惊厥剂量与致死剂量之间的差距，含布比卡因的混合制剂所致惊厥后的存活率尤其提高。结论是局部麻醉药的毒性基本上是相加的。
