Pharmacodynamic models of propofol in children: respiratory and EEG end-points compared

Background: Pediatric pharmacokinetic (PK) models [1, 2] used for target-controlled infusion (TCI) of propofol, frequently employ an effect site equilibration rate constant, ke0, that is derived from adult studies. Pharmacodynamic (PD) differences between adults and children, however, dictate that it is unacceptable to extrapolate available adult PD data to pediatric models. Although pediatric PK data on intravenous anesthetics are available, the availability of pediatric PD data is relatively limited. Previous pediatric PD studies investigating propofol administration in children have described PD models based on the Bispectral Index (BIS)[3] and auditory evoked potential (AEP) monitors. In this work we have identified a pediatric PD model of propofol in children, based on the State Entropy [4](SE)(M-entropy® module; GE Healthcare, Helsinki, Finland) and respiratory responses as clinical end-points.Method: Fifty two ASA category I/II children, scheduled for elective gastrointestinal endoscopic investigation were enrolled. The age and weight were 12+/-2.3 yr and 44+/-14.8 kg, respectively (mean+/-SD). Propofol 1% at a dose of 4mg/kg was administered intravenously using a standard infusion pump (Medex Protégé [start_en] 00AE; 3010; Healthcare Company, Duluth, GA, USA). The rate of infusion for each subject was determined by a randomization schedule in a related study and ranged from 1000 mcg/kg/min to 2300 mcg/kg/min. Eighteen patients were excluded from further analysis due to inadequate measurements. The Paedfusor and Kataria PK models were used to predict the propofol plasma concentration, and the PD models for SE, tidal …