Toxicity

Bupivacaine is more cardiotoxic than equi-effective doses of lidocaine. Clinically, this is manifested by severe ventricular arrhythmias and myocardial depression after inadvertent intravascu-lar administration of large doses of bupivacaine. Bupivacaine dissociates slowly during diastole, so a significant fraction of Na+ channels at physiological heart rates remains blocked with bupi-vacaine at the end of diastole. Thus, the block by bupivacaine is cumulative and substantially more than would be predicted by its local anesthetic potency. Bupivacaine-induced cardiac toxicity can be very difficult to treat, and its severity is enhanced by coexisting acidosis, hypercarbia, and hypoxemia. The S-enantiomer and the racemate are equally efficacious and potent, but lev-obupivacaine may be less cardiotoxic.

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