Interactions of propofol and remifentanil on bispectral index under 66% N(2)O: analysis by dose-effect curve, isobologram, and combination index

BACKGROUND: Propofol and remifentanil are usually co-administered and have shown synergistic effect for anesthesia. However, the synergistic effect of the two drugs on hypnosis measured by bispectral index (BIS) was controversial in previous studies. The aim of this study was to identify the interaction of propofol and remifentanil on BIS and the optimal dose combinations for hypnosis under 66% N(2)O during surgery. METHODS: Patients (age 55-75 and American Society of Anesthesiologists [ASA] 1-2) undergoing gastrectomy were enrolled in this study. Propofol and remifentanil were co-administered incrementally at 1 : 1 potent ratio (the P1R1 group), at 1 : 2 potent ratio (the P1R2 group), or at 2 : 1 potent ratio (the P2R1 group) using effect site target-controlled infusion and BIS was measured. 66% N(2)O was concomitantly administered to all groups. The dose-effect curves, the 90% effective dose (EC(90)) for adequate hypnosis (BIS 40), isobolograms and combination index were obtained by Calcusyn program (Biosoft) to reveal the interaction of propofol and remifentanil. RESULTS: The P2R1 group showed synergistic action on BIS. However, the other groups needed larger amount of each drug than the doses of additive action. The EC(90) of the P2R1 group was propofol, 3.34 µg/ml and remifentanil, 2.41 ng/ml under 66% of N(2)O. CONCLUSIONS: Propofol dominant co-administration is needed for dose reduction in BIS guided hypnosis.