Yamauchi Y, Kotani J, Ueda Y
Department of Anesthesiology, Osaka Dental University, Japan.
J Neurosurg Anesthesiol. 1998 Jul;10(3):178-87. doi: 10.1097/00008506-199807000-00009.
In order to understand why exogenous epinephrine decreases the convulsive dose of lidocaine, the authors investigated cerebral circulation and plasma lidocaine concentrations in Wistar rats under general anesthesia. In the first experiment, baseline evaluations of each rat's electroencephalogram (EEG), mean arterial pressure (MAP), regional cerebral blood flow (r-CBF), cerebrospinal fluid (CSF) pressure, and cerebral perfusion pressure (CPP) were made. The rats were then assigned to one of three groups: Group L (n=6) received intravenous lidocaine (5 mg/kg/min); Group LE (n=6) received intravenous lidocaine (5 mg/kg/min) and epinephrine (2.5 kg/kg/min); and Group E (n=5) received intravenous epinephrine (2.5 microg/kg/min). Cumulative doses of lidocaine at the onset of EEG spike activity in Groups L and LE were compared. Blood-brain barrier (BBB) permeability was evaluated by observing extravasation of Evans blue (EB) dye. In the second experiment, additional rats were allocated to two treatment groups: Group L' (n=6) received intravenous lidocaine (5 mg/kg/min); Group LE' (n=6) received intravenous lidocaine (5 mg/kg/min) and epinephrine (2.5 microg/kg/min). Brain tissue oxygen partial pressure (PtO2) was monitored during infusion, and arterial and sagittal sinus blood samples were obtained immediately after the onset of EEG spike activity to determine plasma lidocaine concentration. The convulsive dose of lidocaine was significantly decreased when lidocaine was administered with epinephrine (Group L: 61.5+/-5.3 mg/kg (mean+/-SD); Group LE: 30.1+/-4.0 mg/kg) (p < 0.05), but there were no significant differences in plasma lidocaine concentration among these groups. R-CBF, CSF pressure, and CPP immediately before EEG spike activity were higher in Group LE than in Group L. Neither decreased PtO2 nor extravasation of EB was observed in rats treated with epinephrine and lidocaine, excluding cerebral ischemia and BBB breakdown from possible mechanisms by which epinephrine decreased the convulsive dose of lidocaine. None of the rats in Group E exhibited EEG findings suggestive of a preconvulsive state, ruling out a convulsive effect of epinephrine itself. The results suggest that an increase in lidocaine supply to the brain caused by increased CBF causes the low cumulative dose of lidocaine at the onset of convulsion in rats given lidocaine plus epinephrine.
为了理解外源性肾上腺素为何会降低利多卡因的惊厥剂量，作者在全身麻醉下对Wistar大鼠的脑循环和血浆利多卡因浓度进行了研究。在第一个实验中，对每只大鼠的脑电图（EEG）、平均动脉压（MAP）、局部脑血流量（r-CBF）、脑脊液（CSF）压力和脑灌注压（CPP）进行了基线评估。然后将大鼠分为三组之一：L组（n = 6）静脉注射利多卡因（5 mg/kg/min）；LE组（n = 6）静脉注射利多卡因（5 mg/kg/min）和肾上腺素（2.5 μg/kg/min）；E组（n = 5）静脉注射肾上腺素（2.5 μg/kg/min）。比较L组和LE组EEG尖峰活动开始时利多卡因的累积剂量。通过观察伊文思蓝（EB）染料的外渗来评估血脑屏障（BBB）的通透性。在第二个实验中，将另外的大鼠分配到两个治疗组：L'组（n = 6）静脉注射利多卡因（5 mg/kg/min）；LE'组（n = 6）静脉注射利多卡因（5 mg/kg/min）和肾上腺素（2.5 μg/kg/min）。在输注过程中监测脑组织氧分压（PtO2），并在EEG尖峰活动开始后立即采集动脉和矢状窦血样以测定血浆利多卡因浓度。当利多卡因与肾上腺素一起给药时，利多卡因的惊厥剂量显著降低（L组：61.5±5.3 mg/kg（平均值±标准差）；LE组：30.1±4.0 mg/kg）（p < 0.05），但这些组之间的血浆利多卡因浓度没有显著差异。EEG尖峰活动前LE组的r-CBF、CSF压力和CPP高于L组。在用肾上腺素和利多卡因治疗的大鼠中，未观察到PtO2降低和EB外渗，排除了脑缺血和BBB破坏是肾上腺素降低利多卡因惊厥剂量的可能机制。E组中没有一只大鼠表现出提示惊厥前期状态的EEG表现，排除了肾上腺素本身的惊厥作用。结果表明，CBF增加导致脑内利多卡因供应增加，从而使给予利多卡因加肾上腺素的大鼠惊厥开始时利多卡因的累积剂量较低。
