Not only bupivacaine but also propofol is sinking in lipid?

Abstract

To the Editor:We read with great interest the recent article [1] and editorial [2] by Oda and Ikeda in this journal. The authors clearly demonstrated the effect of lipid emulsion on central nervous system abnormalities induced by bupivacaine toxicity using the unique experimental in vivo animal model. Although many anesthesiologists in developed countries, including Japan, would prefer to choose safer and long-acting local anesthetics, e.g., ropivacaine, basic research on the mechanism of drug toxicity and exploration of treatment for intoxication are absolutely important.Oda concluded that a lipid sink resulting from administration of the emulsion appears to play an important role for various lipophilic agents. Recently, we demonstrated that the hypnotic activity of propofol, a popular intravenous general anesthetic and one of the most lipophilic drugs, was diminished by simultaneous injection of lipid as a solvent [3]. Injection site pain of propofol is widely known and is considered to result from the increase in free aqueous fraction of the drug [4]. The coadministration of lipid solution could alleviate this pain by the decrease in free propofol caused by the lipid sink. Therefore, we hypothesized that not only injection pain but also the effect of the drugs on the central nervous system might be modified by lipid injection, similar to bupivacaine neurotoxicity.Lipid rescue is reported as effective for many other drugs besides bupivacaine. The precise mechanism is not fully understood, and further studies are required. Reducing pain during propofol injection: the role of the solvent. Conflict of interest

Administration of lipid emulsion reduced the hypnotic potency of propofol more than that of thiamylal in mice

“…We previously found that dilution with a crystalloid solution of Diprivan® enhanced the hypnotic potency of propofol, whereas simultaneous administration of lipid diminished its potency [15,16]. Propofol is a highly lipophilic solvent that is distributed as an emulsified micelle solution [17].…”

The Influence of Differences in Solvents and Concentration on the Efficacy of Propofol at Induction of Anesthesia

“…There is no clear explanation for the results concerning the effect of the concentration. In the preliminary and laboratory animal experiments, we found opposite results that the diluted propofol showed greater potency [ 12 ]. In clinical settings, variability of the effect of propofol might absolutely depend on pathophysiological backgrounds [ 13 ] and the difference of formulations might be negligible.…”