Levobupivacaine - A review of its pharmacology and use as a local anaesthetic

Based an findings that the cardiotoxicity infrequently observed with racemi c bupivacaine shows enantioselectivity, i,e, it is more pronounced with the R(+)-enantiomer, the S(-)-enantiomer (levobupivacaine) has been developed for clinical use as a long acting local anaesthetic. The majority of in vitro, in vitro and human pharmacodynamic studies of ner ve block indicate that levobupivacaine has similar potency to bupivacaine. However, levobupivacaine had a lower risk of cardiovascular and CNS toxicit y than bupivacaine in animal studies. In human volunteers, levobupivacaine had less of a negative inotropic effect and, at intravenous doses >75mg, pr oduced less prolongation of the QT(C) interval than bupivacaine. Fewer chan ges indicative of CNS depression on EEG were evident with levobupivacaine. Levobupivacaine is long acting with a dose-dependent duration of anaesthesi a. The onset of action is less than or equal to 15 minutes with various ana esthetic techniques, In studies of surgical anaesthesia in adults, levobupi vacaine provided sensory block for up to 9 hours after epidural administrat ion of less than or equal to 202.5mg, 6.5 hours after intrathecal 15mg, and 17 hours after brachial plexus block with 2 mg/kg. Randomised, double-blin d clinical studies established that the anaesthetic and/or analgesic effect s of levobupivacaine were largely similar to those of bupivacaine at the sa me dose. Sensory block tended to be longer with levobupivacaine than bupiva caine, amounting to a difference of 13 to 45 minutes with epidural administ ration and approximately 2 hours with peripheral nerve block. With epidural administration, levobupivacaine produced less prolonged motor block than s ensory block. This differential was not seen with peripheral nerve block. C onditions satisfactory for surgery and good pain management were achieved b y use of local infiltration or peribulbar administration of levobupivacaine , Levobupivacaine was generally as effective as bupivacaine for pain manage ment during labour, and was effective for the management of postoperative p ain, especially when combined with clonidine, morphine or fentanyl. The tolerability profiles of levobupivacaine and bupivacaine were very simi lar in clinical trials. No clinically significant ECG abnormalities or seri ous CNS events occurred with the doses used. The most common adverse event associated with levobupivacaine treatment was hypotension (31%). Conclusions: Levobupivacaine is a long acting local anaesthetic with a clin ical profile closely resembling that of bupivacaine. However, current precl inical safety and toxicity data show an advantage for levobupivacaine over bupivacaine. Clinical data comparing levobupivacaine with ropivacaine are n eeded before the role of the drug can be fully established. Excluding pharm acoeconomic considerations, levobupivacaine is an appropriate choice for us e in place of bupivacaine.