Liu P L, Feldman H S, Giasi R, Patterson M K, Covino B G
Anesth Analg. 1983 Apr;62(4):375-9.
The comparative central nervous system (CNS) toxicity of serially administered intravenous doses of lidocaine, bupivacaine, etidocaine, and tetracaine was investigated in awake dogs. The mean cumulative dose required for convulsive activity was 4.0 mg/kg tetracaine, 5.0 mg/kg bupivacaine, 8.0 mg/kg etidocaine, and 22.0 mg/kg lidocaine. The cumulative convulsive dose of lidocaine was significantly greater than that of the other three agents (P less than 0.01). A comparison of the in vivo anesthetic potency and the acute CNS toxicity of these various agents suggests little difference in the therapeutic ratio between less potent anesthetics such as lidocaine and more potent drugs, i.e., tetracaine, bupivacaine, and etidocaine. The relative CNS toxicity of the different agents as determined in awake dogs in this study was compared with their relative cardiovascular toxicity previously evaluated in a series of ventilated dogs anesthetized with pentobarbital. The dose of lidocaine, etidocaine, tetracaine, and bupivacaine required to produce irreversible cardiovascular depression was 3.5-6.7 times greater than that which produced convulsions. These results suggest that the CNS is the primary target organ for the toxic effects of both highly lipid-soluble and highly protein-bound local anesthetics (i.e., bupivacaine, etidocaine, and tetracaine) and less lipid-soluble and less protein-bound drugs (i.e., lidocaine) following rapid intravenous administration.
在清醒犬中研究了静脉连续给予利多卡因、布比卡因、依替卡因和丁卡因时的中枢神经系统（CNS）毒性比较。引起惊厥活动所需的平均累积剂量分别为：丁卡因4.0mg/kg、布比卡因5.0mg/kg、依替卡因8.0mg/kg、利多卡因22.0mg/kg。利多卡因的累积惊厥剂量显著高于其他三种药物（P<0.01）。比较这些不同药物的体内麻醉效能和急性CNS毒性表明，效力较弱的麻醉药如利多卡因与效力较强的药物如丁卡因、布比卡因和依替卡因之间的治疗指数差异不大。将本研究中清醒犬所确定的不同药物的相对CNS毒性与其先前在一系列用戊巴比妥麻醉的通气犬中评估的相对心血管毒性进行比较。产生不可逆心血管抑制所需的利多卡因、依替卡因、丁卡因和布比卡因剂量比引起惊厥的剂量大3.5 - 6.7倍。这些结果表明，快速静脉给药后，CNS是高度脂溶性和高度蛋白结合的局部麻醉药（即布比卡因、依替卡因和丁卡因）以及脂溶性较低和蛋白结合较少的药物（即利多卡因）毒性作用的主要靶器官。
