Emulsion of flurbiprofen axetil reduces propofol injection pain due to a decrease in free propofol concentration

Purpose. Flurbiprofen axetil emulsion (FA), a prodrug of nonsteroidal anti-inflammatory drugs (NSAIDs) that is widely used for perioperative pain relief in Japan, has been effective for reducing propofol injection pain, but the mechanism is unclear. The purpose of this study was to test the hypothesis that the reduction of propofol injection pain by FA may be attributed to a decrease in free propofol concentration. Methods. Diprivan (propofol emulsion; Dipri; AstraZeneca Cheshire, UK) and Propofol-Lipuro (Lipuro; B. Braun: Melsungen, Germany) were used. A randomized double-blind study was performed to compare pain on injection with six kinds of propofol solution: plain Dipri, a 3:1 (v/v) mixture of Dipri and saline (Dipri-S), a 3:1 mixture of Dipri and FA (Dipri-FA), plain Lipuro, a 3:1 mixture of Lipuro and saline (Lipuro-S), and a 3:1 mixture of Lipuro and FA (Lipuro-FA). Three hundred patients (American Society of Anesthesiologists [ASA] physical status [PS] I-II) scheduled for elective surgery received one of these six propofol emulsions (n = 50, each group). Injection pain was evaluated every 10s after the start of a 1-min infusion of up to 2mg(.)kg(-1) propofol. We also measured the in vitro free propofol concentrations of the propofol preparations that we tested (n = 5, each). Results. The mixture of FA with propofol decreased the incidence of injection pain, compared with plain propofol, for Lipuro (P < 0.01) but not for Dipri. The free propofol concentration in each emulsion in vitro was also decreased by mixing the propofol with saline or FA. The incidence of pain was reduced in a free-propofol concentration-dependent manner (R(2) = 0.926). Conclusion. The findings suggest that the reduction of propofol injection pain by FA may be explained, at least in part, by a reduction in the free propofol concentration.