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

Abstract

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, ECG, 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 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.

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.

Figure 1

Amount of levobupivacaine (•) and rac-bupivacaine (○) infused in 14 subjects. The corresponding mean (▪-□) and median (▴-▵) values are shown.

Figure 2

Vital signs at baseline (B) and at different times after the start of i.v. infusion of levobupivacaine (•) and rac-bupivacaine (○) in 14 healthy subjects (mean±s.e. mean).

Figure 3

Cardiovascular variables as assessed by transthoracic electrical bioimpedance at baseline (B) and at different times after the end (E) or the start (S) of the infusion of levobupivacaine (•) and rac-bupivacaine (○) in 14 healthy subjects (mean±s.e. mean).

Figure 4

Semilogarithmic plot of the plasma concentrations (mean±s.e. mean) in 14 healthy subjects at different times after the start of the infusion of levobupivacaine (mean dose: 56.1 mg).