EEG-Based Automatic Classification of ‘Awake’ versus ‘Anesthetized’ State in General Anesthesia Using Granger Causality

BACKGROUND: General anesthesia is a reversible state of unconsciousness and depression of reflexes to afferent stimuli induced by administration of a "cocktail" of chemical agents. The multi-component nature of general anesthesia complicates the identification of the precise mechanisms by which anesthetics disrupt consciousness. Devices that monitor the depth of anesthesia are an important aide for the anesthetist. This paper investigates the use of effective connectivity measures from human electrical brain activity as a means of discriminating between 'awake' and 'anesthetized' state during induction and recovery of consciousness under general anesthesia. METHODOLOGY/PRINCIPAL FINDINGS: Granger Causality (GC), a linear measure of effective connectivity, is utilized in automated classification of 'awake' versus 'anesthetized' state using Linear Discriminant Analysis and Support Vector Machines (with linear and non-linear kernel). Based on our investigations, the most characteristic change of GC observed between the two states is the sharp increase of GC from frontal to posterior regions when the subject was anesthetized, and reversal at recovery of consciousness. Features derived from the GC estimates resulted in classification of 'awake' and 'anesthetized' states in 21 patients with maximum average accuracies of 0.98 and 0.95, during loss and recovery of consciousness respectively. The differences in linear and non-linear classification are not statistically significant, implying that GC features are linearly separable, eliminating the need for a complex and computationally expensive non-linear classifier. In addition, the observed GC patterns are particularly interesting in terms of a physiological interpretation of the disruption of consciousness by anesthetics. Bidirectional interaction or strong unidirectional interaction in the presence of a common input as captured by GC are most likely related to mechanisms of information flow in cortical circuits. CONCLUSIONS/SIGNIFICANCE: GC-based features could be utilized effectively in a device for monitoring depth of anesthesia during surgery

The Effects of Anesthetic Induced Loss of Consciousness on Quantitative Electroen Cephalogram, and Bispectral and Spectral Entropy Indices. Studies on Healthy Male

Changes in the electroencephalography (EEG) signal have been used to study the effects of anesthetic agents on the brain function. Several commercial EEG based anesthesia depth monitors have been developed to measure the level of the hypnotic component of anesthesia. Specific anesthetic related changes can be seen in the EEG, but still it remains difficult to determine whether the subject is consciousness or not during anesthesia. EEG reactivity to external stimuli may be seen in unconsciousness subjects, in anesthesia or even in coma. Changes in regional cerebral blood flow, which can be measured with positron emission tomography (PET), can be used as a surrogate for changes in neuronal activity. The aim of this study was to investigate the effects of dexmedetomidine, propofol, sevoflurane and xenon on the EEG and the behavior of two commercial anesthesia depth monitors, Bispectral Index (BIS) and Entropy. Slowly escalating drug concentrations were used with dexmedetomidine, propofol and sevoflurane. EEG reactivity at clinically determined similar level of consciousness was studied and the performance of BIS and Entropy in differentiating consciousness form unconsciousness was evaluated. Changes in brain activity during emergence from dexmedetomidine and propofol induced unconsciousness were studied using PET imaging. Additionally, the effects of normobaric hyperoxia, induced during denitrogenation prior to xenon anesthesia induction, on the EEG were studied. Dexmedetomidine and propofol caused increases in the low frequency, high amplitude (delta 0.5-4 Hz and theta 4.1-8 Hz) EEG activity during stepwise increased drug concentrations from the awake state to unconsciousness. With sevoflurane, an increase in delta activity was also seen, and an increase in alpha- slow beta (8.1-15 Hz) band power was seen in both propofol and sevoflurane. EEG reactivity to a verbal command in the unconsciousness state was best retained with propofol, and almost disappeared with sevoflurane. The ability of BIS and Entropy to differentiate consciousness from unconsciousness was poor. At the emergence from dexmedetomidine and propofol induced unconsciousness, activation was detected in deep brain structures, but not within the cortex. In xenon anesthesia, EEG band powers increased in delta, theta and alpha (8-12Hz) frequencies. In steady state xenon anesthesia, BIS and Entropy indices were low and these monitors seemed to work well in xenon anesthesia. Normobaric hyperoxia alone did not cause changes in the EEG. All of these results are based on studies in healthy volunteers and their application to clinical practice should be considered carefully.Siirretty Doriast

International healthcare accreditation : an analysis of clinical quality and patient experience in the UAE

A mixed method research design was used to answer the question; ‘does accreditation have an impact on hospital quality, clinical measures and patient experience?’ The thesis contains three study components: 1) A case study determining the predictors of patient experience; 2) a cross-sectional study examining the relationship of hospital accreditation and patient experience and 3) A four year time series analysis of the impact of accreditation on hospital quality using 27 quality measures. A case study analysis of patient experience, using a piloted, validated and reliable survey tool, was conducted in Al Noor Hospital. The survey was administered via face-to-face interviews to 391 patients. Patient demographic variables, stay characteristics and patient experience constructs were tested against five patient experience outcome measures using regression analysis. The predictors of positive patient experience were the patient demographics (age, nationality, and health status), hospital stay characteristics (length of stay and hospital treatment outcome) and patient experience constructs (care from nurses, care from doctors, cleanliness, pain management and quality of food). Recommendations were made on how hospital managers can improve patient experience using these modifiable factors. The cross-sectional study found that accredited hospitals had significantly higher inpatient experience scores than non-accredited hospitals. The hospital level variables, other than patient volume, had no correlations with patient experience. The interrupted time series analysis demonstrated that although accreditation improved the quality performance of the hospital with a residual benefit of 20 percentage points above the baseline level, this improvement was not sustained over the 3-year accreditation cycle. The accreditation life cycle theory was developed as an explanatory framework for the pattern of performance during the accreditation cycle. This theory was consequently supported by empirical evidence. Recommendations were made for improvement of the accreditation process. The Life Cycle Model and time series analysis were proposed as strategic tools for healthcare managers to recognise and prevent the negative trends of the accreditation life cycle in order to sustain improvements gained from accreditation. The findings of the three research components were triangulated to form a theory on the impact of accreditation on clinical quality measures and patient experience. This thesis is important from a research perspective, as healthcare accreditation, although commonly used to improve quality, is still under researched and under theorised. This is the first investigation of accreditation to use interrupted time series analysis, the first analysis on patient experience and hospital accreditation and also the first study on patient experience in the Middle East. Thus it adds to the evidence base of accreditation and patient experience but also has policy and management implications

Parallel recovery of consciousness and sleep in acute traumatic brain injury.

OBJECTIVE: To investigate whether the progressive recuperation of consciousness was associated with the reconsolidation of sleep and wake states in hospitalized patients with acute traumatic brain injury (TBI). METHODS: This study comprised 30 hospitalized patients (age 29.1 ± 13.5 years) in the acute phase of moderate or severe TBI. Testing started 21.0 ± 13.7 days postinjury. Consciousness level and cognitive functioning were assessed daily with the Rancho Los Amigos scale of cognitive functioning (RLA). Sleep and wake cycle characteristics were estimated with continuous wrist actigraphy. Mixed model analyses were performed on 233 days with the RLA (fixed effect) and sleep-wake variables (random effects). Linear contrast analyses were performed in order to verify if consolidation of the sleep and wake states improved linearly with increasing RLA score. RESULTS: Associations were found between scores on the consciousness/cognitive functioning scale and measures of sleep-wake cycle consolidation (p < 0.001), nighttime sleep duration (p = 0.018), and nighttime fragmentation index (p < 0.001). These associations showed strong linear relationships (p < 0.01 for all), revealing that consciousness and cognition improved in parallel with sleep-wake quality. Consolidated 24-hour sleep-wake cycle occurred when patients were able to give context-appropriate, goal-directed responses. CONCLUSIONS: Our results showed that when the brain has not sufficiently recovered a certain level of consciousness, it is also unable to generate a 24-hour sleep-wake cycle and consolidated nighttime sleep. This study contributes to elucidating the pathophysiology of severe sleep-wake cycle alterations in the acute phase of moderate to severe TBI

Assessing rheoencephalography dynamics through analysis of the interactions among brain and cardiac networks during general anesthesia

Cerebral blood flow (CBF) reflects the rate of delivery of arterial blood to the brain. Since no nutrients, oxygen or water can be stored in the cranial cavity due to space and pressure restrictions, a continuous perfusion of the brain is critical for survival. Anesthetic procedures are known to affect cerebral hemodynamics, but CBF is only monitored in critical patients due, among others, to the lack of a continuous and affordable bedside monitor for this purpose. A potential solution through bioelectrical impedance technology, also known as rheoencephalography (REG), is proposed, that could fill the existing gap for a low-cost and effective CBF monitoring tool. The underlying hypothesis is that REG signals carry information on CBF that might be recovered by means of the application of advanced signal processing techniques, allowing to track CBF alterations during anesthetic procedures. The analysis of REG signals was based on geometric features extracted from the time domain in the first place, since this is the standard processing strategy for this type of physiological data. Geometric features were tested to distinguish between different anesthetic depths, and they proved to be capable of tracking cerebral hemodynamic changes during anesthesia. Furthermore, an approach based on Poincaré plot features was proposed, where the reconstructed attractors form REG signals showed significant differences between different anesthetic states. This was a key finding, providing an alternative to standard processing of REG signals and supporting the hypothesis that REG signals do carry CBF information. Furthermore, the analysis of cerebral hemodynamics during anesthetic procedures was performed by means of studying causal relationships between global hemodynamics, cerebral hemodynamics and electroencephalogram (EEG) based-parameters. Interactions were detected during anesthetic drug infusion and patient positioning (Trendelenburg positioning and passive leg raise), providing evidence of the causal coupling between hemodynamics and brain activity. The provided alternative of REG signal processing confirmed the hypothesis that REG signals carry information on CBF. The simplicity of the technology, together with its low cost and easily interpretable outcomes, should provide a new opportunity for REG to reach standard clinical practice. Moreover, causal relationships among the hemodynamic physiological signals and brain activity were assessed, suggesting that the inclusion of REG information in depth of anesthesia monitors could be of valuable use to prevent unwanted CBF alterations during anesthetic procedures.Peer ReviewedPostprint (published version

Breathing Rate Estimation From the Electrocardiogram and Photoplethysmogram: A Review.

Breathing rate (BR) is a key physiological parameter used in a range of clinical settings. Despite its diagnostic and prognostic value, it is still widely measured by counting breaths manually. A plethora of algorithms have been proposed to estimate BR from the electrocardiogram (ECG) and pulse oximetry (photoplethysmogram, PPG) signals. These BR algorithms provide opportunity for automated, electronic, and unobtrusive measurement of BR in both healthcare and fitness monitoring. This paper presents a review of the literature on BR estimation from the ECG and PPG. First, the structure of BR algorithms and the mathematical techniques used at each stage are described. Second, the experimental methodologies that have been used to assess the performance of BR algorithms are reviewed, and a methodological framework for the assessment of BR algorithms is presented. Third, we outline the most pressing directions for future research, including the steps required to use BR algorithms in wearable sensors, remote video monitoring, and clinical practice

Exploring the pharmacodynamics of multidrug combinations and using the advances in technology to individualise anaesthetic drug titration

In current practice, pharmacokinetic-dynamic (PK/PD) models are frequently used to describe the combined relationship between the time course of drug plasma concentrations (PK) and the time independent relationship between the drug concentration at the receptor site and the clinical effect (PD). This thesis contributes to the knowledge in anaesthetic pharmacology and explores the dose-response relationships of propofol and sevoflurane (with and without the coadministration of remifentanil) in greater detail using PK/PD models. Our studies show that PK/PD models are useful in clinical practice. The concept of neural inertia could have an influence on these models, but is still controversial in humans and it does not break down the essence and applicability of these PK/PD models. Subsequently, we used these models to compare the pharmacodynamics of propofol and sevoflurane (with and without remifentanil) at both a population level as well as at an individual level. This comparison let us describe potency ratios between both hypnotics which is very helpful for anaesthetist when switching between these drugs for any reason during a case. We applied the same PK/PD models and similar potency ratios in clinical practice using the SmartPilot® View, a drug advisory system, to guide anaesthetic drug titration, and we assessed its clinical utility. Finally, we evaluated a novel method to analyse the cerebral drug effect on the EEG using Artificial Intelligence in order to explore the feasibility of whether a single index can quantify the hypnotic effect in a drug-independent way

User-centered visual analysis using a hybrid reasoning architecture for intensive care units

One problem pertaining to Intensive Care Unit information systems is that, in some cases, a very dense display of data can result. To ensure the overview and readability of the increasing volumes of data, some special features are required (e.g., data prioritization, clustering, and selection mechanisms) with the application of analytical methods (e.g., temporal data abstraction, principal component analysis, and detection of events). This paper addresses the problem of improving the integration of the visual and analytical methods applied to medical monitoring systems. We present a knowledge- and machine learning-based approach to support the knowledge discovery process with appropriate analytical and visual methods. Its potential benefit to the development of user interfaces for intelligent monitors that can assist with the detection and explanation of new, potentially threatening medical events. The proposed hybrid reasoning architecture provides an interactive graphical user interface to adjust the parameters of the analytical methods based on the users' task at hand. The action sequences performed on the graphical user interface by the user are consolidated in a dynamic knowledge base with specific hybrid reasoning that integrates symbolic and connectionist approaches. These sequences of expert knowledge acquisition can be very efficient for making easier knowledge emergence during a similar experience and positively impact the monitoring of critical situations. The provided graphical user interface incorporating a user-centered visual analysis is exploited to facilitate the natural and effective representation of clinical information for patient care

Advanced multiparametric optimization and control studies for anaesthesia

Anaesthesia is a reversible pharmacological state of the patient where hypnosis, analgesia and muscle relaxation are guaranteed and maintained throughout the surgery. Analgesics block the sensation of pain; hypnotics produce unconsciousness, while muscle relaxants prevent unwanted movement of muscle tone. Controlling the depth of anaesthesia is a very challenging task, as one has to deal with nonlinearity, inter- and intra-patient variability, multivariable characteristics, variable time delays, dynamics dependent on the hypnotic agent, model analysis variability, agent and stability issues. The modelling and automatic control of anaesthesia is believed to (i) benefit the safety of the patient undergoing surgery as side-effects may be reduced by optimizing the drug infusion rates, and (ii) support anaesthetists during critical situations by automating the drug delivery systems. In this work we have developed several advanced explicit/multi-parametric model predictive (mp-MPC) control strategies for the control of depth of anaesthesia. State estimation techniques are developed and used simultaneously with mp-MPC strategies to estimate the state of each individual patient, in an attempt to overcome the challenges of inter- and intra- patient variability, and deal with possible unmeasurable noisy outputs. Strategies to deal with the nonlinearity have been also developed including local linearization, exact linearization as well as a piece-wise linearization of the Hill curve leading to a hybrid formulation of the patient model and thereby the development of multiparametric hybrid model predictive control methodology. To deal with the inter- and intra- patient variability, as well as the noise on the process output, several robust techniques and a multiparametric moving horizon estimation technique have been design and implemented. All the studies described in the thesis are performed on clinical data for a set of 12 patients who underwent general anaesthesia.Open Acces