An In Vitro Analysis of the Effects of Intravenous Lipid Emulsion on Free and Total Local Anaesthetic Concentrations in Human Blood and Plasma

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 avail...

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Main Authors: Louise Ann Clark, Jochen Beyer, Andis Graudins
Format: Article
Language:English
Published: Hindawi Limited 2014-01-01
Series:Critical Care Research and Practice
Online Access:http://dx.doi.org/10.1155/2014/236520
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spelling doaj-ea53e31f074d42419afcd80a86a692db2020-11-25T00:28:48ZengHindawi LimitedCritical Care Research and Practice2090-13052090-13132014-01-01201410.1155/2014/236520236520An In Vitro Analysis of the Effects of Intravenous Lipid Emulsion on Free and Total Local Anaesthetic Concentrations in Human Blood and PlasmaLouise Ann Clark0Jochen Beyer1Andis Graudins2Monash Health Emergency Medicine Program, Monash Medical Centre, Clayton Road, Clayton, VIC 3168, AustraliaDepartment of Forensic Toxicology, Institute of Forensic Medicine, Kantonsspital St. Gallen, Rorschacher Straße 95, Building 11, 9007 St. Gallen, SwitzerlandMonash Health Emergency Medicine Program, Monash Medical Centre, Clayton Road, Clayton, VIC 3168, AustraliaBackground. 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.http://dx.doi.org/10.1155/2014/236520
collection DOAJ
language English
format Article
sources DOAJ
author Louise Ann Clark
Jochen Beyer
Andis Graudins
spellingShingle Louise Ann Clark
Jochen Beyer
Andis Graudins
An In Vitro Analysis of the Effects of Intravenous Lipid Emulsion on Free and Total Local Anaesthetic Concentrations in Human Blood and Plasma
Critical Care Research and Practice
author_facet Louise Ann Clark
Jochen Beyer
Andis Graudins
author_sort Louise Ann Clark
title An In Vitro Analysis of the Effects of Intravenous Lipid Emulsion on Free and Total Local Anaesthetic Concentrations in Human Blood and Plasma
title_short An In Vitro Analysis of the Effects of Intravenous Lipid Emulsion on Free and Total Local Anaesthetic Concentrations in Human Blood and Plasma
title_full An In Vitro Analysis of the Effects of Intravenous Lipid Emulsion on Free and Total Local Anaesthetic Concentrations in Human Blood and Plasma
title_fullStr An In Vitro Analysis of the Effects of Intravenous Lipid Emulsion on Free and Total Local Anaesthetic Concentrations in Human Blood and Plasma
title_full_unstemmed An In Vitro Analysis of the Effects of Intravenous Lipid Emulsion on Free and Total Local Anaesthetic Concentrations in Human Blood and Plasma
title_sort in vitro analysis of the effects of intravenous lipid emulsion on free and total local anaesthetic concentrations in human blood and plasma
publisher Hindawi Limited
series Critical Care Research and Practice
issn 2090-1305
2090-1313
publishDate 2014-01-01
description 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.
url http://dx.doi.org/10.1155/2014/236520
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