Lipid-free Fluoropolymer-based Propofol Emulsions and Lipid Reversal of Propofol Anesthesia in Rats

Abstract

Background Propofol, 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. Methods The 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. Results All 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. Conclusions Three 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.

Effect of intravenous infusion of rocuronium on emergence from propofol anesthesia in rats

“…In general, the time to emergence should be de ned as the time to return of the righting re ex [17,18]. However, because the return of the righting re ex appears after forelimb movement or mastication in experimental animals during the emergence from anesthesia [19], that de nition is inadequate for more invasive studies in which tracheotomy and mechanical ventilation are required.…”

Neuronal mechanisms of adenosine A2A receptors in the loss of consciousness induced by propofol general anesthesia with functional magnetic resonance imaging

“…into the animals before propofol administration. After 15 min, propofol (Parks et al., 2016) (15 mg/kg, Diprivan; AstraZeneca) was administered via the lateral tail vein, and loss of righting reflex (LORR) was measured by rolling the rat onto its back and observing whether the animal was able to right itself. All rats were gently placed in the supine position on a heating pad (to maintain body temperature ~37°C) after losing righting reflex (measured from the start of the 20 s injection).…”

“…On the occasion of the 125th anniversary of the publication of Science , the question was posed of how general anesthetics induce loss of consciousness (LOC) (Kennedy & Norman, 2005), but the mechanism of general anesthesia is not yet well understood (Bademosi et al., 2018), which limits the speed of recovery from general anesthesia. For more than 30 years, propofol, an intravenous anesthetic, has been commonly used for induction and maintenance of general anesthesia (Parks, Tucker, Amlong, Mecozzi, & Pearce, 2016), but the mechanism of action still require further investigation. Thus, propofol was selected as the starting point of general anesthesia research, which has great significance and importance to clinical practice.…”

Intravenous infusion of rocuronium bromide prolongs emergence from propofol anesthesia in rats

“…The time to emergence from propofol anesthesia, defined as the time from flush of the intravenous line at the termination of infusion to the appearance of a sign of emergence, was assessed. In general, the time to emergence should be defined as the time to return of the righting reflex [10,11]. However, because the return of the righting reflex appears after forelimb movement or mastication in experimental animals during emergence from anesthesia [12], that definition should be inadequate for more invasive studies in which tracheotomy and mechanical ventilation are required.…”