Background: This study was conducted to compare the performance accuracy of the independent variables Bispectral Index (BIS), A-Line ARX index (AAI), and predicted propofol effect-site concentration (CePROP) to measure the dependent variables of loss of responses to different stimulation defined as loss of response to verbal command (LORverbal), eyelash reflex (LORlash), and noxious stimulus (LORnoxious) during stepwise increased levels of propofol infusion with and without remifentanil. Methods: Forty-five patients were randomly allocated to one of three groups (0, 2, and 4 ng/ml remifentanil) to receive graded CePROP and predicted effect compartment controlled remifentanil (CeREMI). At every step, the ability to respond to verbal command using the Observer's Assessment of Alertness/Sedation Scale (OAA/S), eyelash reflex, and electrical tetanic noxious stimulus were compared against BIS, AAI, and CePROP. Prediction probability and sensitivity/specificity were calculated. Results: Increasing CeREMI increased BIS and AAI values at LORverbal and LORlash and decreased CePROP. Similar findings were found for LORnoxious. The overall prediction probability to measure the hypnotic component of anesthesia remained accurate in the three groups for BIS, AAI, and CePROP. Combined information from CePROP, CeREMI, and BIS or AAI increased the overall prediction probability for predicting the OAA/S scale and LORlash. Less accuracy to LORnoxious was found in all independent variables. Conclusions: Although BIS, AAI, and CePROP were influenced by remifentanil during propofol administration, their ability to detect OAA/S and LORlash remained accurate. Improved performance is obtained when BIS and AAI are measured in conjunction with drug targeted effect-site concentrations. Remifentanil decreases the ability of these independent variables to detect LORnoxious.

Background: The authors compared the behavior of two calculations of electroencephalographic spectral entropy, state entropy (SE) and response entropy (RE), with the A-Line ARX Index (AAI) and the Bispectral Index (BIS) and as measures of anesthetic drug effect. They compared the measures for baseline variability, burst suppression, and prediction probability. They also developed pharmacodynamic models relating SE, RE, AAI, and BIS to the calculated propofol effect-site concentration (Ceprop). Methods: With institutional review board approval, the authors studied 10 patients. All patients received 50 mg/min propofol until either burst suppression greater than 80% or mean arterial pressure less than 50 mmHg was observed. SE, RE, AAI, and BIS were continuously recorded. Ceprop was calculated from the propofol infusion profile. Baseline variability, prediction of burst suppression, prediction probability, and Spearman rank correlation were calculated for SE, RE, AAI, and BIS. The relations between Ceprop and the electroencephalographic measures of drug effect were estimated using nonlinear mixed effect modeling. Results: Baseline variability was lowest when using SE and RE. Burst suppression was most accurately detected by spectral entropy. Prediction probability and individualized Spearman rank correlation were highest for BIS and lowest for SE. Nonlinear mixed effect modeling generated reasonable models relating all four measures to Ceprop. Conclusions: Compared with BIS and AAI, both SE and RE seem to be useful electroencephalographic measures of anesthetic drug effect, with low baseline variability and accurate burst suppression prediction. The ability of the measures to predict Ceprop was best for BIS.

Target-controlled infusion (TCI) is a technique of infusing IV drugs to achieve a user-defined predicted ("target") drug concentration in a specific body compartment or tissue of interest. In this review, we describe the pharmacokinetic principles of TCI, the development of TCI systems, and technical and regulatory issues addressed in prototype development. We also describe the launch of the current clinically available systems.

For several decades, a number of methods have been developed for the noninvasive assessment of the level of consciousness during general anesthesia. In this paper, detrended fluctuation analysis is used to study the scaling behavior of the electroencephalogram as a measure of the level of consciousness. Three indexes are proposed in order to characterize the patient state. Statistical analysis demonstrates that they allow significant discrimination between the awake, sedated and anesthetized states. Two of them present a good correlation with established indexes of depth of anesthesia. The scaling behavior has been found related to the depth of anesthesia and the methodology allows real-time implementation, which enables its application in monitoring devices

Background: Pharmacokinetic and pharmacodynamic models are used to predict and explore drug infusion schemes and their resulting concentration profiles for clinical application. Our aim was to develop a pharmacokinetic-pharmacodynamic model for remifentanil that is accurate in patients with a wide range of age and weight. Methods: Remifentanil pharmacokinetic data were obtained from three previously published studies of adults and children, one of which also contained pharmacodynamic data from adults. NONMEM was used to estimate allometrically scaled compartmental pharmacokinetic and pharmacodynamic models. Weight, age, height, sex, and body mass index were explored as covariates. Predictive performance was measured across young children, children, young adults, middle-aged, and elderly. Results: Overall, 2,634 remifentanil arterial concentration and 3,989 spectral-edge frequency observations from 131 individuals (55 male, 76 female) were analyzed. Age range was 5 days to 85 yr, weight range was 2.5 to 106 kg, and height range was 49 to 193 cm. The final pharmacokinetic model uses age, weight, and sex as covariates. Parameter estimates for a 35-yr-old, 70-kg male (reference individual) are: V1, 5.81 l; V2, 8.82 l; V3, 5.03 l; CL, 2.58 l/min; Q2, 1.72 l/min; and Q3, 0.124 l/min. Parameters mostly increased with fat-free mass and decreased with age. The pharmacodynamic model effect compartment rate constant (ke0) was 1.09 per minute (reference individual), which decreased with age. Conclusions: We developed a pharmacokinetic-pharmacodynamic model to predict remifentanil concentration and effect for a wide range of patient ages and weights. Performance exceeded the Minto model over a wide age and weight range.