Clinical Information

Bupivacaine (1-butyl-N-[2,6-dimethylphenyl] piperidine-2-carboxamide) is used as a local anesthetic for many surgical procedures, and is injected directly into surgical sites to reduce pain for up to 20 hours postsurgery. As an injectable local anesthetic, the drug is used to effect peripheral, sympathetic, caudal, epidural, or retrobulbar nerve membrane permeability to sodium ions, which results in inhibition of depolarization with resultant conduction blockade.(1)

The onset and duration of anesthesia is route- and dose-dependent, ranging from 1 to 17 minutes and lasting for 2 to 9 hours.(1) The drug is highly protein bound (approximately 95%), and has a volume of distribution (Vd) of 0.4 L/kg to 1.0 L/kg. Bupivacaine under goes significant metabolism; <1% of a dose is excreted unchanged.(2) The half-life elimination is age-dependent: approximately 8 hours in neonates and 1.5 to 5.5 hours in adults.(1)

Serum levels of bupivacaine correlate poorly with anesthesia effect because the drug's distribution out of the injection site is variable. However, serum levels may have value in indicating potential toxicity remote from the injection site. In general, central nervous system (CNS) and cardiovascular events are the primary toxicities and include tremor, tinnitus, dizziness, blurred vision, hypotension, and bradycardia. CNS symptoms of toxicity appear at lower serum levels than do cardiovascular symptoms.(3) Intralipid has been proposed as a treatment for the cardiotoxicity, but neither the optimum dose nor guidelines for intervention have been defined, so its use remains controversial and limited to those cases of cardiotoxicity when cardiopulmonary bypass is the only other option.

The drug is now available as the principally active optical isomer, levobupivacaine (this assay measures levobupivacaine and the racemic mixture [levobupivacaine and bupivacaine] equally). The occurrence of CNS toxicity with use of levobupivacaine is 1.5 to 2.5 times lower than with bupivacaine, from studies in healthy volunteers, with CNS toxicity onset coming at approximately 25% higher doses.(4) Since both drugs are often administered for local anesthesia at levels near the top of the tolerated range, it has proven difficult to objectively assess potency, and there is no clear conclusion as to which drug is more potent.