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

Abstract

BackgroundBlood-brain equilibration rate constant (ke0) is derived from either pharmacokinetic and pharmacodynamic modeling (ke0_model) or a model-independent observed time to peak effect (ke0_tpeak). Performance in bispectral index (BIS) prediction was compared between ke0_model and ke0_tpeak for microemulsion or long chain triglyceride (LCT) propofol.MethodsTime 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 (ke0_model = 0.187/min, group Bmicro = 20) or LCT propofol (ke0_model = 0.26/min, group BLCT = 20) and remifentanil. The ke0_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 ke0_tpeak's. Predicted BIS values calculated by sigmoid Emax equations with ke0_model and ke0_tpeak were compared with observed BIS values during induction and emergence for both formulations of propofol.ResultsObserved 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, ke0_model) and -2.42% (-26.1 to 36.2, ke0_tpeak), while 8.01% (-20.5 to 30.1, ke0_model) and 7.37% (-27.0 to 49.1, ke0_tpeak) in group BLCT. The median absolute performance errors of BIS in group Bmicro were 11.87% (2.2-31.1ke0_model) and 14.38% (-0.6 to 44.6, ke0_tpeak), while 17.31% (5.54-36.0, ke0_model) and 18.28% (-0.1 to 56.0, ke0_tpeak) in group BLCT.ConclusionsThe ke0_model showed better performance in BIS prediction than the ke0_tpeak.

Keywords

• bispectral index
• pharmacokinetic
• propofol