Morishima H O, Pedersen H, Finster M, Sakuma K, Bruce S L, Gutsche B B, Stark R I, Covino B G
Anesthesiology. 1981 Jul;55(1):57-61. doi: 10.1097/00000542-198107000-00012.
The relative central nervous system and cardiovascular toxicity of lidocaine was compared in adult, newborn, and fetal sheep during continuous infusion of lidocaine into the jugular vein at the rate of 2 mg x kg-1 x min-1. An identical sequence of toxic manifestations occurred in the adult, newborn, and fetus: convulsions, hypotension, respiratory arrest, and circulatory collapse. Doses necessary to produce these manifestations were highest in fetuses and lowest in adults. For example, in order to elicit convulsions, 5.8 +/- 1.8 mg/kg of lidocaine was required in the adults, 18.4 +/- 2.2 in the newborns, and 41.9 +/- 6.0 in the fetuses. Measurements of lidocaine concentrations in blood demonstrated that these toxic symptoms occurred at levels which were not significantly different among the three groups. The results indicate that fetal and newborn lambs are no more sensitive to lidocaine toxicity than are adult sheep. The fact that the highest doses were required in the fetuses is probably related to the placental clearance of the drug into mothers and better fetal maintenance of arterial Po2 despite convulsions and respiratory arrest (cessation of breathing-like movements).
在成年、新生和胎儿绵羊中，以2mg·kg⁻¹·min⁻¹的速率持续向颈静脉输注利多卡因，比较了利多卡因对中枢神经系统和心血管系统的相对毒性。成年、新生和胎儿出现了相同顺序的毒性表现：惊厥、低血压、呼吸停止和循环衰竭。产生这些表现所需的剂量在胎儿中最高，在成年人中最低。例如，为了引发惊厥，成年人需要5.8±1.8mg/kg的利多卡因，新生儿需要18.4±2.2mg/kg，胎儿需要41.9±6.0mg/kg。血液中利多卡因浓度的测量表明，这些毒性症状在三组中出现时的水平并无显著差异。结果表明，胎儿和新生羔羊对利多卡因毒性的敏感性并不高于成年绵羊。胎儿需要最高剂量的事实可能与药物经胎盘清除进入母体以及尽管出现惊厥和呼吸停止（呼吸样运动停止）但胎儿仍能较好地维持动脉血氧分压有关。
