CENTRAL NERVOUS AND CARDIOVASCULAR EFFECTS OF IV INFUSIONS OF ROPIVACAINE, BUPIVACAINE AND PLACEBO IN VOLUNTEERS

We have compared the incidence of CNS symptoms and changes in echocard iography and electrophysiology during i.v. infusions of ropivacaine, b upivacaine and placebo. Acute tolerance of i.v. infusion of 10 mg min( -1) was studied in a crossover, randomized, double-blind study in 12 v olunteers previously acquainted with the CNS effects of lignocaine. Th e maximum tolerated dose for CNS symptoms was higher after ropivacaine in nine of 12 subjects and higher after bupivacaine in three subjects . The 95% confidence limits for the difference in mean dose between ro pivacaine and bupivacaine were -30 and 7 mg. The maximum tolerated unb ound arterial plasma concentration was twice as high after ropivacaine (P<0.001). Muscular twitching occurred more frequently after bupivaca ine (P<0.05). The time to disappearance of all symptoms was shorter af ter ropivacaine (P<0.05). A threshold for CNS toxicity was apparent at a mean free plasma concentration of approximately 0.6 mg litre(-1) fo r ropivacaine and 0.3 mg litre(-1) for bupivacaine. Bupivacaine increa sed QRS width during sinus rhythm compared with placebo (P<0.001) and ropivacaine (P<0.01). Bupivacaine reduced both left ventricular systol ic and diastolic function compared with placebo (P<0.05 and P<0.01, re spectively), while ropivacaine reduced only systolic function (P<0.01) .