Do all sedatives promote biological sleep electroencephalogram patterns? A machine learning framework to identify biological sleep promoting sedatives using electroencephalogram.

Background: Sedatives are commonly used to promote sleep in intensive care unit patients. However, it is not clear whether sedation-induced states are similar to the biological sleep. We explored if sedative-induced states resemble biological sleep using multichannel electroencephalogram (EEG) recordings.

Progress in the validation of nociception monitoring in guiding intraoperative analgesic therapy.

Purpose Of Review: This article summarizes the current level of validation for several nociception monitors using a categorized validation process to facilitate the comparison of performance.

Recent Findings: Nociception monitors improve the detection of a shift in the nociception and antinociception balance during anesthesia, guiding perioperative analgesic therapy. A clear overview and comparison of the validation process for these monitors is missing.

General Purpose Pharmacokinetic-Pharmacodynamic Models for Target-Controlled Infusion of Anaesthetic Drugs: A Narrative Review.

Target controlled infusion (TCI) is a clinically-available and widely-used computer-controlled method of drug administration, adjusting the drug titration towards user selected plasma- or effect-site concentrations, calculated according to pharmacokinetic-pharmacodynamic (PKPD) models. Although this technology is clinically available for several anaesthetic drugs, the contemporary commercialised PKPD models suffer from multiple limitations. First, PKPD models for anaesthetic drugs are developed using deliberately selected patient populations, often excluding the more challenging populations, such as children, obese or elderly patients, of whom the body composition or elimination mechanisms may be structurally different compared to the lean adult patient population.

Utility of the SmartPilot® View advisory screen to improve anaesthetic drug titration and postoperative outcomes in clinical practice: a two-centre prospective observational trial.

Background: The advisory system SmartPilot® View (Drägerwerk AG, Lübeck, Germany) provides real-time, demographically adjusted pharmacodynamic information throughout anaesthesia, including time course of effect-site concentrations of administered drugs and a measure of potency of the combined drug effect termed the "'Noxious Stimulation Response Index' (NSRI). This dual-centre, prospective, observational study assesses whether the availability of SmartPilot® View alters the behaviour of anaesthetic drug titration of anaesthetists and improves the Anaesthesia Quality Score (AQS; percentage of time spent with MAP 60-80 mm Hg and Bispectral Index [BIS] 40-60 [blinded]).

Methods: We recruited 493 patients scheduled for elective surgery in two university centres.

Population Pharmacodynamics of Propofol and Sevoflurane in Healthy Volunteers Using a Clinical Score and the Patient State Index: A Crossover Study.

Background: The population pharmacodynamics of propofol and sevoflurane with or without opioids were compared using the endpoints no response to calling the person by name, tolerance to shake and shout, tolerance to tetanic stimulus, and two versions of a processed electroencephalographic measure, the Patient State Index (Patient State Index-1 and Patient State Index-2).

Methods: This is a reanalysis of previously published data. Volunteers received four anesthesia sessions, each with different drug combinations of propofol or sevoflurane, with or without remifentanil.

Novel drug-independent sedation level estimation based on machine learning of quantitative frontal electroencephalogram features in healthy volunteers.

Background: Sedation indicators based on a single quantitative EEG (QEEG) feature have been criticised for their limited performance. We hypothesised that integration of multiple QEEG features into a single sedation-level estimator using a machine learning algorithm could reliably predict levels of sedation, independent of the sedative drug used.

Methods: In total, 102 subjects receiving propofol (N=36; 16 male/20 female), sevoflurane (N=36; 16 male/20 female), or dexmedetomidine (N=30; 15 male/15 female) were included in this study of healthy volunteers.

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.

Neural mass model-based tracking of anesthetic brain states.

Neural mass model-based tracking of brain states from electroencephalographic signals holds the promise of simultaneously tracking brain states while inferring underlying physiological changes in various neuroscientific and clinical applications. Here, neural mass model-based tracking of brain states using the unscented Kalman filter applied to estimate parameters of the Jansen-Rit cortical population model is evaluated through the application of propofol-based anesthetic state monitoring. In particular, 15 subjects underwent propofol anesthesia induction from awake to anesthetised while behavioral responsiveness was monitored and frontal electroencephalographic signals were recorded.

Propofol Breath Monitoring as a Potential Tool to Improve the Prediction of Intraoperative Plasma Concentrations.

Introduction: Monitoring of drug concentrations in breathing gas is routinely being used to individualize drug dosing for the inhalation anesthetics. For intravenous anesthetics however, no decisive evidence in favor of breath concentration monitoring has been presented up until now. At the same time, questions remain with respect to the performance of currently used plasma pharmacokinetic models implemented in target-controlled infusion systems.

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.

Accuracy of the composite variability index as a measure of the balance between nociception and antinociception during anesthesia.

Background: The Composite Variability Index (CVI), derived from the electroencephalogram, was developed to assess the antinociception-nociception balance, whereas the Bispectral Index (BIS) was developed to assess the hypnotic state during anesthesia. We studied the relationships between these indices, level of hypnosis (BIS level), and antinociception (predicted remifentanil effect-site concentrations, CeREMI) before and after stimulation. Also, we measured their association with movement in response to a noxious stimulus.

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.