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Best Paper Prizes 2013

Evidence Review in Emergency Medicine held March 2013 in Terrigal NSW.

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

Louise Clark (1), Jochen Beyer (3), Andis Graudins (1,2)
1) Southern Health Emergency Medicine Program, Monash Medical Centre, Clayton, Victoria.
2) Southern Clinical School, Faculty of Medicine, Nursing and Health Sciences, Monash University, Clayton, Victoria.
3) Victorian Institute of Forensic Medicine, Southbank, Melbourne, Victoria.

Abstract

Background
Intravenous Lipid Emulsion (ILE) is recommended as a ‘rescue’ treatment for local anaesthetic (LA) toxicity. A number of mechanisms of action are theorized, including sequestration of lipophilic LAs into an intravascular ‘lipid-sink’, thus reducing drug concentration. Lipophilicity of LAs is variable and little data are available correlating the effects of ILE on free and total concentrations in human blood or plasma.

Aims
To compare the in-vitro effect of ILE on fall in free- and total-LA concentrations in human blood and plasma. To correlate the fall in LA-concentration to LA lipophilicity.

Method
One of four LAs in known concentrations (Bupivacaine-most lipophilic-4mg/L, Ropivacaine-6mg/L, Lignocaine-14mg/L, Prilocaine-least lipophilic-7mg/L) was introduced to human plasma or whole-blood. ILE or control-buffer was added at three concentrations (2%, 10%, 20%). 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 in the dialysate. Percent fall in LA concentration from control was compared between the LAs and correlated with lipophilicity.

Results
All three ILE concentrations produced a significant reduction in total and free bupivacaine concentration compared with the other LAs (Bup-60% v Ligno-30% v Pril-15% v Ropiv<10%). Ropivacaine had the least reduction in concentration, despite a lipophilicity similar to bupivacaine. Percent-fall in LA concentration increased linearly with increasing lipophilicity when ropivacaine was excluded from this analysis.

Conclusion
This is the 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. The lack of correlation between lipophilicity and the expected fall in ropivacaine concentration with ILE has been observed previously in-vitro in non-blood product models. Despite evidence of reduction in LA concentration in the presence of ILE, our data do not confirm or disprove whether a ‘lipid-sink’ is responsible for reducing LA toxicity in-vivo.


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Tel/Fax: (07) 3134 2272 Email: $Q$jogp@btfn.psh.bv Office Hours: Tues - Thurs 9am - 5pm Fri 9am - 3pm
ABN: 64 231 328 255
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