Consciousness and responsiveness: Lessons from anaesthesia and the vegetative state

peer reviewedPURPOSE OF REVIEW: The aim of this article is to review recent behavioural and neuroimaging studies in anaesthesia and the vegetative state. RECENT FINDINGS: These studies highlight possible dissociations between consciousness and responsiveness in both these states. SUMMARY: We discuss future avenues of research in the field, in order to improve the detection of awareness during anaesthesia and the vegetative state using neuroimaging and neurophysiologic techniques

Protocol for the "Michigan Awareness Control Study": A prospective, randomized, controlled trial comparing electronic alerts based on bispectral index monitoring or minimum alveolar concentration for the prevention of intraoperative awareness

<p>Abstract</p> <p>Background</p> <p>The incidence of intraoperative awareness with explicit recall is 1-2/1000 cases in the United States. The Bispectral Index monitor is an electroencephalographic method of assessing anesthetic depth that has been shown in one prospective study to reduce the incidence of awareness in the high-risk population. In the B-Aware trial, the number needed to treat in order to prevent one case of awareness in the high-risk population was 138. Since the number needed to treat and the associated cost of treatment would be much higher in the general population, the efficacy of the Bispectral Index monitor in preventing awareness in all anesthetized patients needs to be clearly established. This is especially true given the findings of the B-Unaware trial, which demonstrated no significant difference between protocols based on the Bispectral Index monitor or minimum alveolar concentration for the reduction of awareness in high risk patients.</p> <p>Methods/Design</p> <p>To evaluate efficacy in the general population, we are conducting a prospective, randomized, controlled trial comparing the Bispectral Index monitor to a non-electroencephalographic gauge of anesthetic depth. The total recruitment for the study is targeted for 30,000 patients at both low and high risk for awareness. We have developed a novel algorithm that is capable of real-time analysis of our electronic perioperative information system. In one arm of the study, anesthesia providers will receive an electronic page if the Bispectral Index value is >60. In the other arm of the study, anesthesia providers will receive a page if the age-adjusted minimum alveolar concentration is <0.5. Our minimum alveolar concentration algorithm is sensitive to both inhalational anesthetics and intravenous sedative-hypnotic agents.</p> <p>Discussion</p> <p>Awareness during general anesthesia is a persistent problem and the role of the Bispectral Index monitor in its prevention is still unclear. The Michigan Awareness Control Study is the largest prospective trial of awareness prevention ever conducted.</p> <p>Trial Registration</p> <p>Clinical Trial NCT00689091</p

A novel multivariate STeady-state index during general ANesthesia (STAN)

The assessment of the adequacy of general anesthesia for surgery, namely the nociception/anti-nociception balance, has received wide attention from the scientific community. Monitoring systems based on the frontal EEG/EMG, or autonomic state reactions (e.g. heart rate and blood pressure) have been developed aiming to objectively assess this balance. In this study a new multivariate indicator of patients' steady-state during anesthesia (STAN) is proposed, based on wavelet analysis of signals linked to noxious activation. A clinical protocol was designed to analyze precise noxious stimuli (laryngoscopy/intubation, tetanic, and incision), under three different analgesic doses; patients were randomized to receive either remifentanil 2.0, 3.0 or 4.0 ng/ml. ECG, PPG, BP, BIS, EMG and [Formula: see text] were continuously recorded. ECG, PPG and BP were processed to extract beat-to-beat information, and [Formula: see text] curve used to estimate the respiration rate. A combined steady-state index based on wavelet analysis of these variables, was applied and compared between the three study groups and stimuli (Wilcoxon signed ranks, Kruskal-Wallis and Mann-Whitney tests). Following institutional approval and signing the informed consent thirty four patients were enrolled in this study (3 excluded due to signal loss during data collection). The BIS index of the EEG, frontal EMG, heart rate, BP, and PPG wave amplitude changed in response to different noxious stimuli. Laryngoscopy/intubation was the stimulus with the more pronounced response [Formula: see text]. These variables were used in the construction of the combined index STAN; STAN responded adequately to noxious stimuli, with a more pronounced response to laryngoscopy/intubation (18.5-43.1 %, [Formula: see text]), and the attenuation provided by the analgesic, detecting steady-state periods in the different physiological signals analyzed (approximately 50 % of the total study time). A new multivariate approach for the assessment of the patient steady-state during general anesthesia was developed. The proposed wavelet based multivariate index responds adequately to different noxious stimuli, and attenuation provided by the analgesic in a dose-dependent manner for each stimulus analyzed in this study.The first author was supported by a scholarship from the Portuguese Foundation for Science and Technology (FCT SFRH/BD/35879/2007). The authors would also like to acknowledge the support of UISPA—System Integration and Process Automation Unit—Part of the LAETA (Associated Laboratory of Energy, Transports and Aeronautics) a I&D Unit of the Foundation for Science and Technology (FCT), Portugal. FCT support under project PEst-OE/EME/LA0022/2013.info:eu-repo/semantics/publishedVersio

Granger Causality Analysis of Steady-State Electroencephalographic Signals during Propofol-Induced Anaesthesia

Changes in conscious level have been associated with changes in dynamical integration and segregation among distributed brain regions. Recent theoretical developments emphasize changes in directed functional (i.e., causal) connectivity as reflected in quantities such as ‘integrated information’ and ‘causal density’. Here we develop and illustrate a rigorous methodology for assessing causal connectivity from electroencephalographic (EEG) signals using Granger causality (GC). Our method addresses the challenges of non-stationarity and bias by dividing data into short segments and applying permutation analysis. We apply the method to EEG data obtained from subjects undergoing propofol-induced anaesthesia, with signals source-localized to the anterior and posterior cingulate cortices. We found significant increases in bidirectional GC in most subjects during loss-of-consciousness, especially in the beta and gamma frequency ranges. Corroborating a previous analysis we also found increases in synchrony in these ranges; importantly, the Granger causality analysis showed higher inter-subject consistency than the synchrony analysis. Finally, we validate our method using simulated data generated from a model for which GC values can be analytically derived. In summary, our findings advance the methodology of Granger causality analysis of EEG data and carry implications for integrated information and causal density theories of consciousness

Anaesthesia and PET of the Brain

Although drugs have been used to administer general anaesthesia for more than a century and a half, relatively little was known until recently about the molecular and cellular effects of the anaesthetic agents and the neurobiology of anaesthesia. Positron emission tomography (PET) and single-photon emission computed tomography (SPECT) studies have played a valuable role in improving this knowledge. PET studies using 11C-flumazenil binding have been used to demonstrate that the molecular action of some, but not all, of the current anaesthetic agents is mediated via the GABAA receptor. Using different tracers labelled with 18F, 11C and 15O, PET studies have shown the patterns of changes in cerebral metabolism and blood flow associated with different intravenous and volatile anaesthetic agents. Within classes of volatile agents, there are minor variations in patterns. More profound differences are found between classes of agents. Interestingly, all agents cause alterations in the blood flow and metabolism of the thalamus, providing strong support for the hypothesis that the anaesthetic agents interfere with consciousness by interfering with thalamocortical communication.</p

Influence of the postoperative inflammatory response on cognitive decline in elderly patients undergoing on-pump cardiac surgery: a controlled, prospective observational study

BACKGROUND: The role of non-infective inflammatory response (IR) in the aetiology of postoperative cognitive dysfunction (POCD) is still controversial. The aim of this controlled, prospective observational study was to assess the possible relationship between the grade of IR, defined by procalcitonin (PCT) changes, and development of POCD related to cardiac surgery. METHODS: Forty-two patients, who were >/= 60 years of age and scheduled for elective cardiac surgery, were separated into the low inflammatory (LIR) and high inflammatory (HIR) response groups based on their PCT levels measured on the first postoperative day. A matched normative control group of 32 subjects was recruited from primary care practice. The PCT and C-reactive protein (CRP) levels were monitored daily during the first five postoperative days. The cognitive function and mood state were preoperatively tested with a set of five neurocognitive tests and two mood inventories and at the seventh postoperative day. The Reliable Change Index modified for practice (RCIp) using data from normative controls was applied to determine the significant decline in test performance. RESULTS: The LIR (n = 20) and HIR (n = 22) groups differed significantly in the PCT (p 0.05). Additionally, there was no difference in the mood states, anxiety levels and perioperative parameters known to influence the development of POCD. CONCLUSIONS: In this study, the magnitude of the non-infective inflammatory response generated by on-pump cardiac surgery did not influence the development of POCD in the early postoperative period in elderly patients

Hippocampal - diencephalic - cingulate networks for memory and emotion: An anatomical guide

This review brings together current knowledge from tract tracing studies to update and reconsider those limbic connections initially highlighted by Papez for their presumed role in emotion. These connections link hippocampal and parahippocampal regions with the mammillary bodies, the anterior thalamic nuclei, and the cingulate gyrus, all structures now strongly implicated in memory functions. An additional goal of this review is to describe the routes taken by the various connections within this network. The original descriptions of these limbic connections saw their interconnecting pathways forming a serial circuit that began and finished in the hippocampal formation. It is now clear that with the exception of the mammillary bodies, these various sites are multiply interconnected with each other, including many reciprocal connections. In addition, these same connections are topographically organised, creating further subsystems. This complex pattern of connectivity helps explain the difficulty of interpreting the functional outcome of damage to any individual site within the network. For these same reasons, Papez’s initial concept of a loop beginning and ending in the hippocampal formation needs to be seen as a much more complex system of hippocampal–diencephalic–cingulate connections. The functions of these multiple interactions might be better viewed as principally providing efferent information from the posterior medial temporal lobe. Both a subcortical diencephalic route (via the fornix) and a cortical cingulate route (via retrosplenial cortex) can be distinguished. These routes provide indirect pathways for hippocampal interactions with prefrontal cortex, with the preponderance of both sets of connections arising from the more posterior hippocampal regions. These multi-stage connections complement the direct hippocampal projections to prefrontal cortex, which principally arise from the anterior hippocampus, thereby creating longitudinal functional differences along the anterior–posterior plane of the hippocampus