title: An in vitro analysis of the effects of intravenous lipid emulsion on free and total local anaesthetic concentrations in human blood and plasma.
abstract: Background. Intravenous lipid emulsion (ILE) is recommended as a "rescue" treatment for local anaesthetic (LA) toxicity. A purported mechanism of action suggests that lipophilic LAs are sequestered into an intravascular "lipid-sink," thus reducing free drug concentration. There is limited data available correlating the effects of ILE on LAs. Aims. To compare the in vitro effect of ILE on LA concentrations in human blood/plasma and to correlate this reduction to LA lipophilicity. Method. One of four LAs (bupivacaine-most lipophilic-4 mg/L, ropivacaine-6 mg/L, lignocaine-14 mg/L, and prilocaine-least lipophilic-7 mg/L) was spiked into plasma or whole blood. ILE or control-buffer was added. Plasma was centrifuged to separate ILE and total-LA concentration assayed from the lipid-free fraction. Whole blood underwent equilibrium dialysis and free-LA concentration was measured. Percent reduction in LA concentration from control was compared between the LAs and correlated with lipophilicity. Results. ILE caused a significant reduction in total and free bupivacaine concentration compared with the other LAs. Ropivacaine had the least reduction in concentration, despite a lipophilicity similar to bupivacaine. The reduction in LA concentration correlated to increasing lipophilicity when ropivacaine was excluded from analysis. Conclusion. In this first in vitro model assessing both free- and total-LA concentrations exposed to ILE in human blood/plasma, ILE effect was linearly correlated with increasing lipophilicity for all but ropivacaine.
authors.affiliation: Monash Health Emergency Medicine Program, Monash Medical Centre, Clayton Road, Clayton, VIC 3168, Australia.
authors.forename: Louise Ann
authors.initials: LA
authors.lastname: Clark
authors.affiliation: Department of Forensic Toxicology, Institute of Forensic Medicine, Kantonsspital St. Gallen, Rorschacher Straße 95, Building 11, 9007 St. Gallen, Switzerland ; Department of Forensic Medicine, Victorian Institute of Forensic Medicine, Monash University, 57-83 Kavanagh Street, Southbank, VIC 3006, Australia.
authors.forename: Jochen
authors.initials: J
authors.lastname: Beyer
authors.affiliation: Monash Health Emergency Medicine Program, Monash Medical Centre, Clayton Road, Clayton, VIC 3168, Australia ; School of Clinical Sciences at Monash Health, Monash University, Clayton, VIC 3168, Australia.
authors.forename: Andis
authors.identifier: 0000-0002-0310-3983
authors.initials: A
authors.lastname: Graudins