A comparison of the cardiovascular effects of levobupivacaine and rac-bupivacaine following intravenous administration to healthy volunteers

被引:306
作者
Bardsley, H
Gristwood, R
Baker, H
Watson, N
Nimmo, W
机构
[1] Chirosci Ltd, Cambridge CB4 4WE, England
[2] Inveresk Clin Res Ltd, Edinburgh, Midlothian, Scotland
关键词
levobupivacaine; rac-bupivacaine; cardiovascular function; S(-) enantiomer; volunteers;
D O I
10.1046/j.1365-2125.1998.00775.x
中图分类号
R9 [药学];
学科分类号
1007 [药学];
摘要
Aims 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. Methods 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, EGG, ejection fraction, acceleration index, stroke index and cardiac index. Results 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 mu g 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 udc-bupivacaine appeared to be greater the difference between the two drugs was not significant. Conclusions 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.
引用
收藏
页码:245 / 249
页数:5
相关论文
共 20 条
[1]
TOXICOLOGICAL AND LOCAL ANESTHETIC EFFECTS OF OPTICALLY ACTIVE ISOMERS OF 2 LOCAL ANESTHETIC COMPOUNDS [J].
ABERG, G .
ACTA PHARMACOLOGICA ET TOXICOLOGICA, 1972, 31 (04) :273-&
[2]
HEXAMETHONIUM AND MIDAZOLAM TERMINATE DYSRHYTHMIAS AND HYPERTENSION CAUSED BY INTRACEREBROVENTRICULAR BUPIVACAINE IN RABBITS [J].
BERNARDS, CM ;
ARTRU, AA .
ANESTHESIOLOGY, 1991, 74 (01) :89-96
[3]
QUANTITATIVE SENSORY EXAMINATION OF EPIDURAL-ANESTHESIA AND ANALGESIA IN MAN - DOSE-RESPONSE EFFECT OF BUPIVACAINE [J].
BRENNUM, J ;
NIELSEN, PT ;
HORN, A ;
ARENDTNIELSEN, L ;
SECHER, NH .
PAIN, 1994, 56 (03) :315-326
[4]
BUPIVACAINE INHIBITS CYCLIC-3',5'-ADENOSINE MONOPHOSPHATE PRODUCTION - A POSSIBLE CONTRIBUTING FACTOR TO CARDIOVASCULAR TOXICITY [J].
BUTTERWORTH, JF ;
BROWNLOW, RC ;
LEITH, JP ;
PRIELIPP, RC ;
COLE, LR .
ANESTHESIOLOGY, 1993, 79 (01) :88-95
[5]
Covino BG., 1988, NEURAL BLOCKADE CLIN, P111
[6]
COYLE DE, 1994, ANESTH ANALG, V79, P335
[7]
CRANDELL JT, 1985, ANESTH ANALG, V64, P204
[8]
de Jong RH, 1994, LOCAL ANAESTHETICS
[9]
DENSON DD, 1992, REGION ANESTH, V17, P311
[10]
GRAF BM, 1995, ANESTHESIOLOGY, V83, pA304