Bupivacaine Toxicity Increases Transmural Dispersion of Repolarization, Developing of a Brugada-like Pattern and Ventricular Arrhythmias, Which is Reversed by Lipid Emulsion Administration. Study in an Experimental Porcine Model
Unintentional administration of bupivacaine may be associated with electrocardiogram changes that promote the development cardiac arrhythmias. Ventricular repolarization markers (corrected QT, QT dispersion, Tpeak–Tend and Tpeak–Tend dispersion) are useful to predict cardiac arrhythmias. We aim to investigate the effects of bupivacaine on the transmural dispersion of repolarization and their reversion following intravenous lipid emulsion (ILE) administration. Fourteen pigs were anaesthetized with thiopental and sevoflurane and underwent tracheal intubation. After instrumentation, a 4 mg kg-bolus of bupivacaine was administrated followed by an infusion of 100 µg kg−1 min−1. QT interval, QTc:QT corrected by heart rate, Tpeak-to-Tend interval and QT and Tpeak-to-Tend dispersion were determined in a sequential fashion: after bupivacaine (at 1 min, 5 min and 10 min) and after ILE (1.5 mL kg−1 over 1 min followed by an infusion of 0.25 mL kg−1 min−1). Three additional animals received only ILE (control group). Bupivacaine significantly prolonged QT interval (∆:36%), QT dispersion (∆:68%), Tpeak-to-Tend (∆:163%) and Tpeak-to-Tend dispersion (∆:98%), from baseline to 10 min. Dispersion of repolarization was related to lethal arrhythmias [three events, including asystole, sustained ventricular tachycardia (VT)] and repeated non-sustained VT (4/14, 28%). A Brugada-like-ECG pattern was visualized at V1–4 leads in 5/14 pigs (35%). ILE significantly decreased the alterations induced by bupivacaine, with the termination of VT within 10 min. No ECG changes were observed in control group. Bupivacaine toxicity is associated with an increase of transmural dispersion of repolarization, the occurrence of a Brugada-like pattern and malignant VA. ILE reverses the changes in dispersion of repolarization, favouring the disappearance of the Brugada-like pattern and VT.
KeywordsBupivacaine Transmural dispersion of repolarisation Brugada-like Lipid emulsions
We thank Conn Hastings, PhD, from Edanz Group (http://www.edanzediting.com/ac) for editing a draft of this manuscript.
This work was supported by a research Grant from the Ministry of Economy, Industry and Competitiveness of Spain, and Fondos FEDER. Reference: 11/00575.
Compliance with Ethical Standards
Conflict of interest
The authors declare no conflicts of interest related with this manuscript.
All applicable international, national, and/or institutional guidelines for the care and use of animals were followed.
- 8.Castle, N. A. (1990). Bupivacaine inhibits the transient outward K+ current but not the inward rectifier in rat ventricular myocytes. Journal of Pharmacology and Experimental Therapeutics, 255, 1038–1046.Google Scholar
- 9.Castro Hevia, J., Antzelevitch, C., Tornés Bárzaga, F., Dorantes Sánchez, M., Dorticós Balea, F., Zayas Molina, R., et al. (2006). Tpeak–Tend and Tpeak–Tend dispersion as risk factors for ventricular tachycardia/ventricular fibrillation in patients with the Brugada syndrome. Journal of the American College of Cardiology, 47, 1828–1834.CrossRefGoogle Scholar
- 18.Lefrant, J. Y., de La Coussaye, J. E., Ripart, J., Muller, L., Lalourcey, L., Peray, P. A., et al. (2001). The comparative electrophysiologic and hemodynamic effects of a large dose of ropivacaine and bupivacaine in anesthetized and ventilated piglets. Anesthesia & Analgesia, 93, 1598–1605.CrossRefGoogle Scholar
- 27.Tse, G., Li, K. H. C., Li, G., Liu, T., Bazoukis, G., Wong, W. T., et al. (2018). Higher dispersion measures of conduction and repolarization in type 1 compared to non-type 1 brugada syndrome patients: An electrocardiographic study from a single center. Front Cardiovasc Med, 4, 132.CrossRefGoogle Scholar
- 31.Zaballos, M., Sevilla, R., González, J., Callejo, D., de Diego, C., Almendral, J., et al. (2016). Analysis of the temporal regression of the QRS widening induced by bupivacaine after Intralipid administration. Study in an experimental porcine model. Revista Española de Anestesiología y Reanimación, 63, 13–21.CrossRefGoogle Scholar