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

TLDR

The study compared the cardiovascular effects of levobupivacaine and rac‑bupivacaine following intravenous administration in healthy male volunteers. In a randomized, double‑blind crossover design, 14 healthy men received 10 mg min⁻¹ infusions of each drug until CNS symptoms or 150 mg total, with arterial blood pressure, heart rate, ECG, ejection fraction, acceleration index, stroke index and cardiac index recorded; mean doses were 56.1 mg for levobupivacaine and 47.9 mg for rac‑bupivacaine with peak plasma concentrations of 2.62 and 2.25 µg ml⁻¹. Levobupivacaine produced significantly smaller reductions in stroke index, acceleration index and ejection fraction compared with rac‑bupivacaine, indicating a less pronounced negative inotropic effect, while both drugs caused small, non‑significant increases in PR and QT intervals.

Abstract

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.