The effects of local anesthetics on bile flow, potassium equilibrium and oxygen consumption in the perfused rat liver.
Amide local anesthetics mainly undergo hepatic metabolism. Specific applications, such as catheter application for long-term pain therapy, may result in large plasma concentrations. As it is unknown whether local anesthetics influence liver function, we examined the influence of lidocaine, bupivacaine, and ropivacaine in concentrations of 1 and 10 microg/mL on the metabolic activity of the perfused rat liver. At the large concentrations, all three local anesthetics caused an immediate increase of oxygen consumption. Bupivacaine and ropivacaine also transiently reduced potassium release. All drugs increased bile flow; this choleretic effect was also significant for bupivacaine and lidocaine in smaller concentrations. In the smaller concentration, only lidocaine significantly increased oxygen consumption. No significant changes in hepatic venous pH were observed. The results show that acute administration of all three local anesthetics results in significant changes of functional variables of the liver. The observed effects appear to result from mitochondrial uncoupling, uptake of the drugs, biliary secretion of their metabolites, and from inhibition of potassium channels. The data provide no evidence that these acute changes may result in enduring postoperative disturbances of liver function, such as cholestasis or jaundice.
Felleiter
Peter
P
Department of Intensive Care Medicine, Swiss Paraplegic-Centre Nottwil, Switzerland. peter.felleiter@paranet.ch
Lierz
Peter
P
Graf
Jürg
J
D000577:Amides / Q000494:pharmacology; D000779:Anesthetics, Local / Q000494:pharmacology*; D000818:Animals; D001646:Bile / Q000187:drug effects* / Q000502:physiology; D002045:Bupivacaine / Q000494:pharmacology; D006863:Hydrogen-Ion Concentration; D066298:In Vitro Techniques; D008012:Lidocaine / Q000494:pharmacology; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D010101:Oxygen Consumption / Q000187:drug effects*; D011188:Potassium / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D000077212:Ropivacaine
D000577:Amides; D000779:Anesthetics, Local; D000077212:Ropivacaine; D008012:Lidocaine; D011188:Potassium; D002045:Bupivacaine