• Colby L Parks, William Tucker, Corey A Amlong, Sandro Mecozzi, and Robert A Pearce.
• From the Department of Anesthesiology (C.L.P., C.A.A., R.A.P.), Department of Chemistry (W.T., S.M.), School of Pharmacy (S.M.), University of Wisconsin-Madison, Madison, Wisconsin.
• Anesthesiology. 2016 Jun 1; 124 (6): 1328-37.

BackgroundPropofol, as a lipid-based emulsion, is effective at inducing anesthesia. It does, however, suffer from several drawbacks, including microbial growth, hyperlipidemia, and pain on injection. In this study, the authors examined the ability of four lipid-free propofol nanoemulsions to induce anesthesia in rats and tested whether a subsequent lipid bolus would accelerate emergence from anesthesia.MethodsThe authors administered five formulations of propofol intravenously to six rats, delivering five different doses five times each, in a repeated-measures randomized crossover design and measured time to loss and recovery of righting reflex. The formulations included (1) Diprivan (AstraZeneca, United Kingdom); (2) L3, incorporating a semifluorinated surfactant plus egg lecithin; (3) B8, incorporating a semifluorinated surfactant only; (4) F8, incorporating a semifluorinated surfactant plus perfluorooctyl bromide; and (5) L80, incorporating egg lecithin only. In a second phase of the study, the authors administered a lipid bolus immediately after a dose of B8 or Diprivan.ResultsAll formulations except L80 impaired the righting reflex without apparent toxic effects. The authors estimated the threshold dose for induction by determining the x-intercept of the linear regression between time to recovery versus log dose. Threshold doses ranged from 5.8 (95% CI, 5.5 to 6.2) to 8.6 (95% CI, 7.2 to 10.2) mg/kg. A 15 ml/kg lipid bolus resulted in an accelerated clearance.ConclusionsThree of the four novel lipid-free fluoropolymer-based formulations showed efficacy in producing anesthesia, which was comparable to that of Diprivan, and a lipid bolus hastened recovery. These novel propofol formulations have the potential to avoid complications seen with the existing lipid-based formulation.

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