Levobupivacaine base and levobupivacaine hydrochloride.

Editor—The British Journal of Anaesthesia has published six papers comparing the effects of levobupivacaine, the S(–)stereoisomer of bupivacaine with bupivacaine and ropivacaine, between 1998 and 2004, and three papers on various aspects of levobupivacaine alone. None of these papers calculated the concentration according to molarity. Two of them noted that there is a difference between the clinical and molar concentrations of levobupivacaine that needs to be considered when comparing it with racemic bupivacaine or ropivacaine. In a third paper, it was mentioned in the methodology that bupivacaine hydrochloride was compared with levobupivacaine base. The authors of the other papers, along with the majority of authors of published studies of levobupivacaine appear not to have considered that the label of the commercially available levobupivacaine (Chirocaine ) indicates the concentration of the base of the molecule, and not, as in the case of other amide-linked local anaesthetics such as racemic bupivacaine and ropivacaine, the concentration of the hydrochloride of the molecule. Since the molecular weight of hydrogen chloride is 36.46, it will make a difference of 12.6% in the concentration of levobupivacaine between a concentration calculated as base or hydrochloride. It follows that, for example 5 mg ml 1 (0.5%) concentration of levobupivacaine base is equivalent to 5.63 mg ml 1 (0.563%) of levobupivacaine hydrochloride, which is then erroneously compared with 5 mg ml 1 of ropivacaine or bupivacaine hydrochloride in the studies. Although this has been pointed as early as in 1998 in this journal, and again by Schug in another anaesthesia journal in 2001, and the commercial product label of Chirocaine clearly states the concentration of the base of the molecule, the 12.6% difference in concentration seems still to be ignored both by investigators and clinicians. As a consequence, the results of levobupivacaine compared with the same concentration of bupivacaine or ropivacaine in most regional anesthetic block studies need to be reinterpreted. It is of note that some of these studies have identified a 17% (P<0.04) and a 19% (not significant) potency difference in favour of levobupivacaine, which might be partially explained by this erroneous calculation.