The fentanyl concentration required for immobility under propofol anesthesia is reduced by pre-treatment with flurbiprofen axetil

We hypothesized that nonsteroidal anti-inflammatory drugs decrease the plasma fentanyl concentration required to produce immobility in 50% of patients in response to skin incision (Cp50_incision) compared with placebo under target-controlled infusion (TCI) propofol anesthesia.

Sixty-two unpremedicated patients scheduled to undergo gynecologic laparoscopy were randomly assigned to receive placebo (control group) or flurbiprofen axetil 1 mg·kg⁻¹ (flurbiprofen group) preoperatively. General anesthesia was induced with fentanyl and propofol, and intubation was performed after succinylcholine 1 mg·kg⁻¹. Propofol was administered via a target-controlled infusion (TCI) system (Diprifusor™) set at an effect-site concentration of 5 μg·mL⁻¹. Fentanyl was given by a TCI system using the STANPUMP software (Schafer model). The concentration for the first patient was set at 3 ng·mL⁻¹ and modified in each group according to the up-down method. Skin incision was performed after more than ten minutes equilibration time. Serum fentanyl concentration, bispectral index (BIS), and hemodynamic parameters were measured two minutes before and after skin incision. The Cp50_incision of fentanyl was derived from the mean of the crossovers (i.e., the serum fentanyl concentrations of successive participants who responded and those who did not or vice versa).

Ten and 11 independent crossover pairs were collected in the control and flurbiprofen groups, respectively, representing 42 of 62 enrolled patients. The mean (SD) fentanyl Cp50_incision was less in the flurbiprofen group [0.84 (0.63) ng·mL⁻¹] than in the control group [1.65 (1.15) ng·mL⁻¹]; P = 0.007; however, there were no differences in BIS, blood pressure, or heart rate, between groups.

Preoperative flurbiprofen axetil decreased the Cp50_incision of fentanyl by 49% during propofol anesthesia without changing the BIS or hemodynamic variables.