Tracking Electroencephalographic Changes Using Distributions of Linear Models: Application to Propofol-Based Depth of Anesthesia Monitoring.

Objective: Tracking brain states with electrophysiological measurements often relies on short-term averages of extracted features and this may not adequately capture the variability of brain dynamics. The objective is to assess the hypotheses that this can be overcome by tracking distributions of linear models using anesthesia data, and that anesthetic brain state tracking performance of linear models is comparable to that of a high performing depth of anesthesia monitoring feature.

Methods: Individuals' brain states are classified by comparing the distribution of linear (auto-regressive moving average-ARMA) model parameters estimated from electroencephalographic (EEG) data obtained with a sliding window to distributions of linear model parameters for each brain state.

Model-based drug administration: current status of target-controlled infusion and closed-loop control.

Purpose Of Review: Drug administration might be optimized by incorporating pharmacokinetic-dynamic (PK/PD) principles and control engineering theories. This review gives an update of the actual status of target-controlled infusion (TCI) and closed-loop computer-controlled drug administration and the ongoing research in the field.

Recent Findings: TCI is becoming mature technology clinically used in many countries nowadays with proven safety.

The History of Target-Controlled Infusion.

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.

Comparisons of Electroencephalographically Derived Measures of Hypnosis and Antinociception in Response to Standardized Stimuli During Target-Controlled Propofol-Remifentanil Anesthesia.

Background: Current electroencephalogram (EEG)-derived measures provide information on cortical activity and hypnosis but are less accurate regarding subcortical activity, which is expected to vary with the degree of antinociception. Recently, the neurophysiologically based EEG measures of cortical input (CI) and cortical state (CS) have been shown to be prospective indicators of analgesia/antinociception and hypnosis, respectively. In this study, we compared CI and an alternate measure of CS, the composite cortical state (CCS), with the Bispectral Index (BIS) and another recently developed measure of antinociception, the composite variability index (CVI).

Development of an Optimized Pharmacokinetic Model of Dexmedetomidine Using Target-controlled Infusion in Healthy Volunteers.

Background: Several pharmacokinetic models are available for dexmedetomidine, but these have been shown to underestimate plasma concentrations. Most were developed with data from patients during the postoperative phase and/or in intensive care, making them susceptible to errors due to drug interactions. The aim of this study is to improve on existing models using data from healthy volunteers.

Differential effects of phenylephrine and norepinephrine on peripheral tissue oxygenation during general anaesthesia: A randomised controlled trial.

Background: Phenylephrine and norepinephrine are two vasopressors commonly used to counteract anaesthesia-induced hypotension. Their dissimilar working mechanisms may differentially affect the macro and microcirculation, and ultimately tissue oxygenation.

Objectives: We investigated the differential effect of phenylephrine and norepinephrine on the heart rate (HR), stroke volume (SV), cardiac index (CI), cerebral tissue oxygenation (SctO2) and peripheral tissue oxygenation (SptO2), and rate-pressure product (RPP).

Analysis of remifentanil with liquid chromatography-tandem mass spectrometry and an extensive stability investigation in EDTA whole blood and acidified EDTA plasma.

Background: Remifentanil is a μ-opioid receptor agonist that was developed as a synthetic opioid for use in anesthesia and intensive care medicine. Remifentanil is rapidly metabolized in both blood and tissues, which results in a very short duration of action. Even after blood sampling, remifentanil is unstable in whole blood and plasma through endogenous esterases and chemical hydrolysis.

A response surface model approach for continuous measures of hypnotic and analgesic effect during sevoflurane-remifentanil interaction: quantifying the pharmacodynamic shift evoked by stimulation.

Background: The authors studied the interaction between sevoflurane and remifentanil on bispectral index (BIS), state entropy (SE), response entropy (RE), Composite Variability Index, and Surgical Pleth Index, by using a response surface methodology. The authors also studied the influence of stimulation on this interaction.

Methods: Forty patients received combined concentrations of remifentanil (0 to 12 ng/ml) and sevoflurane (0.

Interaction between nitrous oxide, sevoflurane, and opioids: a response surface approach.

Background: The interaction of sevoflurane and opioids can be described by response surface modeling using the hierarchical model. We expanded this for combined administration of sevoflurane, opioids, and 66 vol.% nitrous oxide (N2O), using historical data on the motor and hemodynamic responsiveness to incision, the minimal alveolar concentration, and minimal alveolar concentration to block autonomic reflexes to nociceptive stimuli, respectively.

Auto-mutual information function of the EEG as a measure of depth of anesthesia.

Monitoring the depth of anesthesia (DOA) is necessary in order to decrease the incident of awareness in anesthesia and to prevent delays in the recovery phase. In the last decades a number of noninvasive methods have been proposed for the analysis of the electroencephalogram (EEG) for monitoring DOA. The objective of this work was to apply auto mutual information function (AMIF) to EEGs of patients under anesthesia in order to find variables able to characterize the following 4 states: awake, sedated, anesthetized and burst suppression episodes.

Sevoflurane remifentanil interaction: comparison of different response surface models.

Background: Various pharmacodynamic response surface models have been developed to quantitatively describe the relationship between two or more drug concentrations with their combined clinical effect. We examined the interaction of remifentanil and sevoflurane on the probability of tolerance to shake and shout, tetanic stimulation, laryngeal mask airway insertion, and laryngoscopy in patients to compare the performance of five different response surface models.

Methods: Forty patients preoperatively received different combined concentrations of remifentanil (0-12 ng/ml) and sevoflurane (0.

Assessment of the depth of anesthesia based on symbolic dynamics of the EEG.

Methodologies based on symbolic dynamics have successfully demonstrated to reflect the nonlinear behavior of biological signals. In the present study, symbolic dynamics was applied to the electroencephalogram (EEG) in order to describe the level of depth of anesthesia. The EEG was transformed to symbol sequences.

Propofol and remifentanil differentially modulate frontal electroencephalographic activity.

Background: The purpose of this study was to evaluate a new, physiologically inspired method for the analysis of the electroencephalogram during propofol-remifentanil anesthesia. Based on fixed-order autoregressive moving-average modeling, this method was hypothesized to be capable of dissociating the effects that hypnotic and analgesic agents have on brain electrical activity.

Methods: Raw electroencephalographic waves from a previously published study were reanalyzed.

Depth of anesthesia index using cumulative power spectrum.

Over the last ten years, monitors of depth of anesthesia have progressively been integrated in the clinical practice. Based on the analysis of the electroencephalogram (EEG), these monitors deliver an index that helps the anesthesiologist to determine the state of the patient during the surgery. Although they employ different kind of algorithms, spectral parameters are always taken into account to achieve the final indexes.

Detrended fluctuation analysis of EEG as a measure of depth of anesthesia.

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.

The effects of ketamine and rocuronium on the A-Line auditory evoked potential index, Bispectral Index, and spectral entropy monitor during steady state propofol and remifentanil anesthesia.

Background: The authors studied the effects of ketamine and rocuronium on the Bispectral Index, A-Line auditory evoked potential index, state entropy, and response entropy during a calculated steady state anesthesia with propofol and remifentanil.

Methods: After ethics committee approval, 42 patients were allocated to four groups. Baseline measurements were performed after implementing a calculated steady state anesthesia with propofol and remifentanil.

New composite index based on midlatency auditory evoked potential and electroencephalographic parameters to optimize correlation with propofol effect site concentration: comparison with bispectral index and solitary used fast extracting auditory evoked potential index.

Background: This study investigates the accuracy of a composite index, the A-Line(R) auditory evoked potentials index version 1.6 (AAI1.6; Danmeter A/S, Odense, Denmark), as a measure of cerebral anesthetic drug effect in a model for predicting a calculated effect site concentration of propofol (CePROP).

Remifentanil used to supplement propofol does not improve quality of sedation during spontaneous respiration.

Study Objective: To evaluate whether the use of remifentanil to supplement propofol during spontaneous respiration confers any benefits in terms of quality of sedation and recovery, or in terms of reduction in propofol requirements.

Design: Prospective, randomized, double-blind study.

Setting: University hospital.