Enhancement by ischemia of the risk of cardiac disorders, especially fibrillation, in regional anesthesia with bupivacaine

Abstract

The impairment of intraventricular conduction by bupivacaine may result in reentrant arrhythmias including ventricular fibrillation. The concentrations responsible for serious accidents are high (5.0 to 8.0 micrograms/ml), but likely to be lowered by myocardial ischemia which gives rise to similar disorders. Therefore we did an electrophysiological study of bupivacaine's effects in an ischemic area of the myocardium. Monophasic action potential (MAP) of the ventricular myocardium was recorded in 30 anesthetized, open-chest pigs. Conduction time and effective refractory period were also measured. Data were obtained during short periods (10-15 s) of pacing at 180 beats/min, but ventricular beats remained governed by the sinus node in the intervals. Ischemia was produced by occluding the left anterior descending coronary artery completely but transiently (up to 8 min), not far from its origin. Comparison was made between the effects of bupivacaine i.v. (n = 10), ischemia (n = 10) and both factors (n = 10). Two min after injection of bupivacaine 2.0 mg/kg (plasma levels 2.0-3.0 micrograms/ml), the duration of MAP was only slightly (7.5-15%) prolonged and its ischemia-induced shortening only slightly attenuated by bupivacaine. At the same time, conduction time was considerably (75-150%) lengthened and its ischemia-induced lengthening enhanced, so that ventricular fibrillation induced by coronary occlusion occurred sooner (about 100 instead of 300 s) in the presence of bupivacaine. Consequently, bupivacaine should be used only with caution in individuals whose myocardium is ischemic or liable to ischemia episodes.

Interaction of Local Anesthetics with Biomembranes Consisting of Phospholipids and Cholesterol: Mechanistic and Clinical Implications for Anesthetic and Cardiotoxic Effects

“…Pacini et al [67] revealed that the effect of lidocaine on sheep Purkinje fibers is greater under simulated ischemia than that in normal conditions. Freysz et al [68] also reported that the risk of cardiac disorders in bupivacaine anesthesia was increased by ischemia. However, the detailed mechanism remains unclear for the local anesthetic cardiotoxicity altered by ischemia.…”

Electrophysiological, haemodynamic, and mitochondrial alterations induced by levobupivacaine during myocardial ischemia in a pig model: protection by lipid emulsions?

“…In addition, myocardial ischemia significantly increases the risk for VF following accidental intravascular LA injection. Previous experiments in our laboratory have shown a close correlation between VF propensity and myocardial ischemia with both bupivacaine [7] and ropivacaine [8].…”

Supplemental Studies for Cardiovascular Risk Assessment in Safety Pharmacology: A Critical Overview

“…As example, in vivo and in vitro models using ischemic/reperfused and/or hypoxic conditions have successfully evidenced the proarrhythmic potential of several therapeutic classes of compounds such as K-ATP channel activators [115,137], Class I antiarrhythmics [138][139][140][141] or anesthetics [142,143]. Despite their recognized comprehensive and predictive value, these models remain however difficult to run routinely.…”