Title Page Electrocardiographic and Hemodynamic Effects of Intravenous Infusion of Bupivacaine, Ropivacaine, Levobupivacaine and Lidocaine in Anesthetized Ewes

Background and Objectives: Neural blockade techniques are associated with a risk of acute cardiac toxicity after accidental intravenous (IV) injection of local anesthetics (LAs). The aim of this study was to compare electrocardiographic (ECG) and hemodynamic (HEM) effects induced by IV infusion of LAs in an anesthetized ewe model. Methods: Thirty-two anesthetized ewes received IV bupivacaine (BUPI), ropivacaine (ROPI), or levobupivacaine (S-BUPI) at an equimolar dose, or lidocaine (LIDO) at a three fold higher rate (n=8 in each group). Intervals RR, PR, QRS, QT, corrected QT (QTc), changes in systolic and diastolic arterial pressure (ΔSAP and ΔDAP) and in myocardial contractility (ΔdP/dt), were assessed every 30 seconds for 7 min. From main ECG variables (RR, PR, QRS, QT), we proposed to use multiple correspondence analysis (MCA) and hierarchical ascending classification (HAC) to explore the structure of statistical dependencies among those measurements, and to determine the different patterns of ECG and HEM changes induced by infusion of BUPI, ROPI, S-BUPI and LIDO. Results: Graphic representation of MCA associated BUPI with the most pronounced modifications in ECG and HEM variables, followed in decreasing order by ROPI, S-BUPI, LIDO. Comparisons of clusters identified by HAC confirmed this classification for ECG variables. Ventricular tachycardia occurred only in BUPI group. Conclusion: In our anesthetized ewe model, high dose IV infusion of BUPI induced the most marked changes in RR, PR, QRS, QT, QTC intervals, ΔSAP and ΔdP/dt. ROPI altered ECG variables less than BUPI but more than S-BUPI. LIDO was associated with the smallest changes.