Investigating propofol-sufentanil interaction using clinical endpoints and processed electroencephalography: a prospective randomized controlled trial.

Abstract

Propofol and sufentanil target controlled infusion technology is used with increasing frequency. Drug interaction modelling, using clinical endpoints and processed electroencephalography helps determine optimal drug concentrations to assure adequate anesthesia. Sixty patients were randomized to receive a constant concentration of sufentanil (0.25 ng/mL (Group S0.25), 0.5 ng/mL (Group S0.5), 0 ng/mL (Group S0). Propofol was administered in steps of 0.5 µg/mL, up to 4 µg/mL. Processed EEG (Bispectral Index, Narcotrend Index) and auditory evoked potentials (composite A-Line autoregressive Index; cAAI), were recorded simultaneously. Sufentanil-propofol interaction was assessed by Probit - and nonlinear regression analysis. Sufentanil had a dose-dependent synergistic effect on the effect-site concentration of propofol (µg/mL) associated with a 50% probability (EC50) of loss of responsiveness to verbal command (S0: 2.84 µg/mL, R2 0.773; S0.25: 1.95 µg/mL, R2 0.862; S0.5: 1.48 µg/mL, R2 0.887) and noxious stimulation (S0: 3.46 µg/mL, R2 0.626 µg/mL; S0.25: 2.17 µg/mL, R2 0.853; S0.5: 1.69 µg/mL, R2 0.897). Non-linear regression analysis revealed a synergistic sufentanil effect on the propofol EC50 for BIS (S0: 3.36 µg/mL, R2 0.79; S0.25: 2.77 µg/mL, R2 0.86 µg/mL; S0.5: 2.6 µg/mL, R2 0.84), Narcotrend Index (S0: 3.57 µg/mL, R2 0.66; S0.25: 2.91 µg/mL, R2 0.70; S0.5: 2.02 µg/mL, R2 0.51) and cAAI (S0: 3.42 µg/mL, R2 0.59; S0.25: 3.00 µg/mL, R2 0.63; S0.5: 3.14 µg/mL, R2 0.59). Sufentanil has a synergistic effect on the clinically observed hypnotic properties of propofol. These findings apply also to the depth of hypnosis measured by the Bispectral Index, Narcotrend Index and cAAI.