The comparison of predictive performance in bispectral index prediction during target effect-site controlled infusion of propofol using different blood effect-site equilibration rate constants in the same pharmacokinetic model

BACKGROUND Blood-brain equilibration rate constant (ke0 ) is derived from either pharmacokinetic and pharmacodynamic modeling (k e0_model) or a model-independent observed time to peak effect (k e0_tpeak). Performance in bispectral index (BIS) prediction was compared between k e0_model and k e0_tpeak for microemulsion or long chain triglyceride (LCT) propofol. METHODS Time to peak effect (tpeak, time to a maximally reduced BIS value) of microemulsion propofol after an intravenous bolus (1 mg/kg) was measured in 100 patients (group Amicro). An observed tpeak of 1.6 min for LCT propofol was obtained from an earlier study. Another 40 patients received a target controlled infusions of microemulsion propofol (k e0_model = 0.187/min, group Bmicro = 20) or LCT propofol (k e0_model = 0.26/min, group BLCT = 20) and remifentanil. The k e0_tpeak's in group Bmicro and BLCT were calculated using the observed tpeak value obtained from group Amicro and 1.6 min, respectively. Effect-site concentrations of propofol were recalculated using the amounts of propofol infused over time and k e0_tpeak's. Predicted BIS values calculated by sigmoid Emax equations with k e0_model and k e0_tpeak were compared with observed BIS values during induction and emergence for both formulations of propofol. RESULTS Observed tpeak of microemulsion propofol was 1.68 min. The median performance errors of BIS in group Bmicro were -1.83% (-24.8 to 18.9, k e0_model) and -2.42% (-26.1 to 36.2, k e0_tpeak), while 8.01% (-20.5 to 30.1, k e0_model) and 7.37% (-27.0 to 49.1, k e0_tpeak) in group BLCT. The median absolute performance errors of BIS in group Bmicro were 11.87% (2.2-31.1k e0_model) and 14.38% (-0.6 to 44.6, k e0_tpeak), while 17.31% (5.54-36.0, k e0_model) and 18.28% (-0.1 to 56.0, k e0_tpeak) in group BLCT. CONCLUSIONS The k e0_model showed better performance in BIS prediction than the k e0_tpeak.