Bardsley H, Gristwood R, Baker H, Watson N, Nimmo W
Chiroscience Ltd, Cambridge, England.
Br J Clin Pharmacol. 1998 Sep;46(3):245-9. doi: 10.1046/j.1365-2125.1998.00775.x.
The aim of this study was to compare the cardiovascular effects of levobupivacaine with those of rac-bupivacaine following i.v. administration to 14 healthy male volunteers.
Drugs were infused (at 10 mg min(-1)) using a randomized, double-blind, complete crossover procedure with a washout period of at least 1 week. The administration of drug was discontinued on the appearance of defined CNS symptoms or when a total of 150 mg had been given. Parameters measured were arterial blood pressure, heart rate, ECG, ejection fraction, acceleration index, stroke index and cardiac index.
The mean doses administered were 56.1 mg and 47.9 mg for levobupivacaine and rac-bupivacaine respectively and the maximum mean plasma concentrations were 2.62 and 2.25 microg ml(-1) respectively. Despite the dose and plasma concentrations being comparable, levobupivacaine produced a statistically significant smaller reduction in mean stroke index (-5.14 vs -11.86 ml m(-2), P=0.001), acceleration index (-0.09 vs -0.20 s(-2), P=0.011) and the ejection fraction (-2.50 vs -4.29%, P=0.024). Both levobupivacaine (non significant) and rac-bupivacaine (significant) produced small increases in the PR interval and the corrected QT interval and although the effects of rac-bupivacaine appeared to be greater the difference between the two drugs was not significant.
In conclusion, this study has shown that following i.v. administration levobupivacaine produces significantly less effects on cardiovascular function than does rac-bupivacaine. In particular the negative inotropic effect for levobupivacaine was less than that for rac-bupivacaine as indicated by changes in stroke index, acceleration index and ejection fraction.
本研究旨在比较左旋布比卡因与消旋布比卡因静脉注射给药后对14名健康男性志愿者心血管系统的影响。
采用随机、双盲、完全交叉试验设计，以10mg/min(-1)的速度输注药物，洗脱期至少1周。当出现明确的中枢神经系统症状或给药总量达到150mg时停止给药。测量的参数包括动脉血压、心率、心电图、射血分数、加速度指数、每搏指数和心脏指数。
左旋布比卡因和消旋布比卡因的平均给药剂量分别为56.1mg和47.9mg，最大平均血浆浓度分别为2.62和2.25μg/ml(-1)。尽管剂量和血浆浓度相当，但左旋布比卡因导致平均每搏指数（-5.14 vs -11.86ml/m(-2)，P=0.001）、加速度指数（-0.09 vs -0.20s(-2)，P=0.011）和射血分数（-2.50 vs -4.29%，P=0.024）的降低在统计学上显著更小。左旋布比卡因（无显著性差异）和消旋布比卡因（有显著性差异）均使PR间期和校正QT间期略有延长，尽管消旋布比卡因的作用似乎更大，但两种药物之间的差异不显著。
总之，本研究表明静脉注射后，左旋布比卡因对心血管功能的影响明显小于消旋布比卡因。特别是，如每搏指数、加速度指数和射血分数的变化所示，左旋布比卡因的负性肌力作用小于消旋布比卡因。
