Morishima H O, Finster M, Arthur G R, Covino B G
Department of Anesthesiology, College of Physicians and Surgeons, Columbia University, New York, NY.
Am J Obstet Gynecol. 1990 May;162(5):1320-4. doi: 10.1016/0002-9378(90)90045-9.
Pregnant sheep are more vulnerable to the toxic effects of bupivacaine, a potent local anesthetic, than are nonpregnant sheep. In contrast, ovine pregnancy does not enhance the toxicity of mepivacaine, a drug with properties similar to lidocaine. We studied the central nervous and cardiovascular toxicity of lidocaine in pregnant sheep receiving a continuous intravenous drug infusion at the rate of 2 mg/kg/min and compared our results with data previously obtained in nonpregnant ewes. In all animals, toxic manifestations occurred in the following sequence: convulsions, hypotension, respiratory arrest, and circulatory collapse. The doses of lidocaine required to produce these symptoms in pregnant and nonpregnant ewes were similar. Convulsions occurred at 5.9 +/- 0.6 mg/kg (mean +/- SE) in the pregnant ewe and 5.8 +/- 1.8 mg/kg in the nonpregnant ewe, whereas circulatory collapse occurred at 40.7 +/- 2.6 and 36.7 +/- 3.3 mg/kg in the pregnant and nonpregnant animals, respectively. Lidocaine plasma concentrations associated with the onset of convulsions in both pregnant and nonpregnant ewes were almost identical (12.1 +/- 0.7 and 11.7 +/- 2.0 micrograms/ml, respectively). At circulatory collapse, these concentrations were 35.1 +/- 3.2 and 41.2 +/- 6.7 micrograms/ml, respectively. It appears that pregnancy does not enhance the toxic effects of lidocaine. These findings are similar to those for mepivacaine but not for bupivacaine, and may be related in part to differences in the way pregnancy affects serum protein binding of these drugs.
与未怀孕的绵羊相比,怀孕的绵羊更容易受到布比卡因(一种强效局部麻醉剂)的毒性影响。相比之下,绵羊怀孕并不会增强甲哌卡因(一种性质与利多卡因相似的药物)的毒性。我们研究了以2毫克/千克/分钟的速率持续静脉输注药物的怀孕绵羊体内利多卡因的中枢神经和心血管毒性,并将我们的结果与之前在未怀孕母羊身上获得的数据进行了比较。在所有动物中,毒性表现按以下顺序出现:惊厥、低血压、呼吸骤停和循环衰竭。在怀孕和未怀孕母羊中产生这些症状所需的利多卡因剂量相似。怀孕母羊惊厥发生时的剂量为5.9±0.6毫克/千克(平均值±标准误),未怀孕母羊为5.8±1.8毫克/千克,而怀孕和未怀孕动物循环衰竭发生时的剂量分别为40.7±2.6和36.7±3.3毫克/千克。怀孕和未怀孕母羊惊厥发作时的利多卡因血浆浓度几乎相同(分别为12.1±0.7和11.7±2.0微克/毫升)。在循环衰竭时,这些浓度分别为35.1±3.2和41.2±6.7微克/毫升。看来怀孕并不会增强利多卡因的毒性作用。这些发现与甲哌卡因的情况相似,但与布比卡因不同,可能部分与怀孕影响这些药物血清蛋白结合的方式差异有关。