Flurbiprofen axetil preceded by venous occlusion in the prevention of pain on propofol injection in the hand: a prospective, randomized, double-blind, vehicle-controlled, dose-finding study in Japanese adult surgical patients.

BACKGROUND: Pain on injection is still a major problem with propofol used for general anesthesia. A number of techniques for reducing propofol-induced pain on injection have been tried, with variable results. Flurbiprofen axetil, a prodrug of the nonsteroidal anti-inflammatory drug flurbiprofen, has been used for postoperative pain management but has not been studied for managing pain on injection of propofol when preceded with venous occlusion.
OBJECTIVE: The present study was undertaken to examine the efficacy of flurbiprofen axetil for reducing pain on propofol injection in Japanese adult surgical patients.
METHODS: This prospective, randomized, double-blind, vehicle-controlled, dose-finding study was conducted at the Department of Anesthesiology, University of Tsukuba Institute of Clinical Medicine, Tsukuba, Japan. Japanese patients aged 18 to 65 years scheduled to undergo elective surgery were eligible. Patients were randomized to receive flurbiprofen axetil IV at 1 of 3 doses (25, 50, or 75 mg), or vehicle (control group), preceded by manual venous occlusion with a rubber tourniquet for 2 minutes and followed by administration of 25% of the total calculated dose of propofol (2 mg/kg), injected into the largest vein of the hand through a 20-gauge IV cannula. During propofol injection, a researcher who was blinded to treatment assignment asked each patient about his or her pain at the injection site. Responses were scored on a 4-point scale (0 = none, 1 = mild, 2 = moderate, 3 = severe). Median pain intensity scores in each group were determined. Adverse effects (AEs) at the injection site (pain, edema, wheal, or inflammation) were monitored for up to 24 hours after surgery.
RESULTS: A total of 120 patients (62 men, 58 women; mean [SD] age, 41 [12] years, mean [SD] height, 162 [8] cm; mean [SD] body weight, 58 [10] kg) were enrolled. Each treatment group comprised 30 patients. No significant between-group differences in demographic characteristics were found. A significantly higher proportion of patients in the control group (77%) experienced pain compared with the flurbiprofen axetil 50- and 75-mg groups (47% and 43%, respectively; both, P < 0.01). The median pain intensity scores were significantly lower in the flurbiprofen axetil 50- and 75-mg groups (both, 0 [no pain]) compared with controls (2 [moderate]; both, P < 0.01). The incidence and intensity of propofol-induced pain were statistically similar between the flurbiprofen axetil 25-mg and control groups. The incidence and intensity of pain associated with the injection of propofol were significantly lower in the flurbiprofen axetil 50- and 75-mg groups compared with the 25-mg group (incidence, 70% [both, P < 0.05]; median pain intensity score, 1 [mild] [both, P < 0.01]). No AEs were observed.
CONCLUSION: In this study of Japanese adult surgical patients, flurbiprofen axetil at doses of 50 and 75 mg, preceded by venous occlusion for 2 minutes, was found to be effective in reducing propofol-induced pain on injection.

RCT Entities:   Population Interventions Outcomes