Anesth Analg 2006;103:1045-1046
© 2006 International Anesthesia Research Society
doi: 10.1213/01.ane.0000239020.08399.98
LETTER TO THE EDITOR
Editor-in-Chief Steven L. Shafer
Local Anesthetic Effect on Liver Function
Berend Mets, MB, ChB, PhD,FRCA, FFA(SA), and
Eric A. Walker, Professor and Chair
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
- Felleiter P, Liersz P, Graf J. The effects of local anesthetics on bile flow, potassium equilibrium and oxygen consumption in the perfused rat liver. Anesth Analg 2006;102:473–7.[Abstract/Free Full Text]
- Mets B, Hickman R, Neveling U, et al. Effect of lidocaine on in vivo hepatic function. Dig Dis Sci 1993;38:2163–9.[Web of Science][Medline]
- Tygstrup N, Funding J, Juul-Nielsen J, et al. The function of the isolated perfused and the in vivo pig liver. Scand J Gastroenterol Suppl 1971;9:131–8.[Medline]
- Sinha V, Brendel K, Mayersohn M. A simplified isolated perfused rat liver apparatus: characterization and measurement of extraction ratios of selected compounds. Life Sci 2000;66:1795–804.[Web of Science][Medline]
- Mets B, Hickman R, Allin R, et al. Effect of hypoxia on the hepatic metabolism of lidocaine in the isolated perfused pig liver. Hepatology 1993;17:668–76.[Web of Science][Medline]
- Stenson RE, Constantino RT, Harrison DC. Interrelationships of hepatic blood flow, cardiac output, and blood levels of lidocaine in man. Circulation 1971;43:205–11.[Abstract/Free Full Text]
- Gariepy L, Fenyves D, Villeneuve JP. Propranolol disposition in the rat: variation in hepatic extraction with unbound drug fraction. J Pharm Sci 1992;81:255–8.[Web of Science][Medline]
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