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Department of Anesthesiology; Penn State College of Medicine; Penn State Milton S. Hershey Medical Center; Hershey, PA; bmets{at}psu.edu (Mets, Walker)
To the Editor:
Felleiter et al.'s (1) recent study of the effects of local anesthetics on isolated perfused rat liver function is motivated in part by the statement "it is unknown whether local anesthetics influence liver function." This study evaluates the effects of two concentrations (1 and 10 µg/mL) of lidocaine, bupivicaine, and ropivicaine on in vitro hepatic function. Their study used at least three naive rat livers for each combination. The authors found that lidocaine was associated with increased hepatic oxygen consumption and bile flow.
These results differ from an in vivo study of the effects of lidocaine on hepatic function in transhepatically cannulated anesthetized pigs (2). In the latter study, lidocaine was infused to achieve a steady-state concentration of 5.9 ± 1.1 µg/mL (x ± sd, n = 7). Lidocaine infusion made no difference in hepatic oxygen consumption or bile flow when compared with saline control. Going further, this study demonstrated no differences between lidocaine- and saline-treated groups in either porcine hepatic energy charge (from biopsies taken to assess adenine nucleotide status) nor hepatic blood flow.
The discrepancies between these two studies may relate to the animal model used or to the established fact that isolated and in vivo liver function are different (3). With respect to the animal model used, the in vitro lidocaine hepatic extraction ratio for the rat is 0.91 (4) compared with 0.63 for the pig (5), which more closely resembles the extraction ratio of 0.66 in vivo in humans (6). An alternative explanation for the investigators' findings might be that they demonstrated a nonspecific effect, not related to the structure of local anesthetics, but simply related secondarily to the administration of a substrate highly metabolized by the rat liver. It might be important for the investigators to study, as a control, a congener highly extracted by the liver, such as propranolol (7) administered in equimolar quantities, but without local anesthetic structure or effect, to exclude nonspecific metabolism itself as an explanation for their results.
Footnotes
Dr. Felleiter does not wish to respond.
REFERENCES
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