Bupivacaine accentuates the cardiovascular depressant effects of verapamil in conscious dogs.
To investigate the potential risk of regional anaesthesia in a verapamil-treated patient, the cardiovascular effects of a combined intravenous infusion of bupivacaine and verapamil were studied in seven conscious and chronically instrumented dogs and were compared to those obtained when each drug was infused separately in the same animals. During verapamil infusion, the decrease in arterial pressure and myocardial contractile force, and the increase in heart rate were constant during the infusion. The lengthening of PR interval correlated with the plasma level of verapamil. During infusion of bupivacaine alone, there was an increase in heart rate and arterial pressure at the end of infusion, whereas the initial depression of myocardial contractile force was compensated. PR interval remained unchanged throughout the infusion of bupivacaine. During combined infusion of bupivacaine and verapamil, there was a time-dependent decrease in heart rate, arterial pressure and myocardial contractile force. A further increase in PR interval correlated with verapamil plasma concentrations which were higher than when verapamil was infused alone; bupivacaine plasma levels were in the same range as during bupivacaine infusion alone. Short periods of second-degree atrioventricular block developed in three out of the seven dogs but no relation was found between QT interval and heart rate in the whole group. Calcium chloride during bupivacaine-verapamil returned heart rate, arterial pressure and myocardial contractile force to their control values within 5 min. Atrioventricular block disappeared and PR interval was shortened following administration of calcium. Bupivacaine and verapamil have additive cardiovascular effects which lead to atrioventricular conduction dysfunction. The effects, at these doses, are reversed by calcium chloride.
D000818:Animals; D002045:Bupivacaine / Q000097:blood / Q000633:toxicity*; D002122:Calcium Chloride / Q000494:pharmacology; D004285:Dogs; D004347:Drug Interactions; D006439:Hemodynamics / Q000187:drug effects*; D007262:Infusions, Intravenous; D011897:Random Allocation; D014700:Verapamil / Q000097:blood / Q000494:pharmacology*
D014700:Verapamil; D002122:Calcium Chloride; D002045:Bupivacaine