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.