Study protocol: Cerebral characterization of sensory gating in disconnected dreaming states during propofol anesthesia using fMRI.

Background: Disconnected consciousness describes a state in which subjective experience (i.e., consciousness) becomes isolated from the external world. It appears frequently during sleep or sedation, when subjective experiences remain vivid but are unaffected by external stimuli. Traditional methods of differentiating connected and disconnected consciousness, such as relying on behavioral responsiveness or on post-anesthesia reports, have demonstrated limited accuracy: unresponsiveness has been shown to not necessarily equate to unconsciousness and amnesic effects of anesthesia and sleep can impair explicit recollection of events occurred during sleep/sedation. Due to these methodological challenges, our understanding of the neural mechanisms underlying sensory disconnection remains limited. Methods: To overcome these methodological challenges, we employ a distinctive strategy by combining a serial awakening paradigm with auditory stimulation during mild propofol sedation. While under sedation, participants are systematically exposed to auditory stimuli and questioned about their subjective experience (to assess consciousness) and their awareness of the sounds (to evaluate connectedness/disconnectedness from the environment). The data collected through interviews are used to categorize participants into connected and disconnected consciousness states. This method circumvents the requirement for responsiveness in assessing consciousness and mitigates amnesic effects of anesthesia as participants are questioned while still under sedation. Functional MRI data are concurrently collected to investigate cerebral activity patterns during connected and disconnected states, to elucidate sensory disconnection neural gating mechanisms. We examine whether this gating mechanism resides at the thalamic level or results from disruptions in information propagation to higher cortices. Furthermore, we explore the potential role of slow-wave activity (SWA) in inducing disconnected consciousness by quantifying high-frequency BOLD oscillations, a known correlate of slow-wave activity. Discussion: This study represents a notable advancement in the investigation of sensory disconnection. The serial awakening paradigm effectively mitigates amnesic effects by collecting reports immediately after regaining responsiveness, while still under sedation. Ultimately, this research holds the potential to understand how sensory gating is achieved at the neural level. These biomarkers might be relevant for the development of sensitive anesthesia monitoring to avoid intraoperative connected consciousness and for the assessment of patients suffering from pathologically reduced consciousness. Clinical trial registration: European Union Drug Regulating Authorities Clinical Trials Database (EudraCT), identifier 2020-003524-17.

The nature of consciousness in anaesthesia.

Neuroscientists agree on the value of locating the source of consciousness within the brain. Anaesthesiologists are no exception, and have their own operational definition of consciousness based on phenomenological observations during anaesthesia. The full functional correlates of consciousness are yet to be precisely identified, however rapidly evolving progress in this scientific domain has yielded several theories that attempt to model the generation of consciousness. They have received variable support from experimental observations, including those involving anaesthesia and its ability to reversibly modulate different aspects of consciousness. Aside from the interest in a better understanding of the mechanisms of consciousness, exploring the functional tenets of the phenomenological consciousness states of general anaesthesia has the potential to ultimately improve patient management. It could facilitate the design of specific monitoring devices and approaches, aiming at reliably detecting each of the possible states of consciousness during an anaesthetic procedure, including total absence of mental content (unconsciousness), and internal awareness (sensation of self and internal thoughts) with or without conscious perception of the environment (connected or disconnected consciousness, respectively). Indeed, it must be noted that unresponsiveness is not sufficient to infer absence of connectedness or even absence of consciousness. This narrative review presents the current knowledge in this field from a system-level, underlining the contribution of anaesthesia studies in supporting theories of consciousness, and proposing directions for future research.

Connected consciousness after tracheal intubation in young adults: an international multicentre cohort study.

BACKGROUND: Connected consciousness, assessed by response to command, occurs in at least 5% of general anaesthetic procedures and perhaps more often in young people. Our primary objective was to establish the incidence of connected consciousness after tracheal intubation in young people aged 18-40 yr. The secondary objectives were to assess the nature of these responses, identify relevant risk factors, and determine their relationship to postoperative outcomes. METHODS: This was an international, multicentre prospective cohort study using the isolated forearm technique to assess connected consciousness shortly after tracheal intubation. RESULTS: Of 344 enrolled subjects, 338 completed the study (mean age, 30 [standard deviation, 6.3] yr; 232 [69%] female). Responses after intubation occurred in 37/338 subjects (11%). Females (13%, 31/232) responded more often than males (6%, 6/106). In logistic regression, the risk of responsiveness was increased with female sex (odds ratio [ORadjusted]=2.7; 95% confidence interval [CI], 1.1-7.6; P=0.022) and was decreased with continuous anaesthesia before laryngoscopy (ORadjusted=0.43; 95% CI, 0.20-0.96; P=0.041). Responses were more likely to occur after a command to respond (and not to nonsense, 13 subjects) than after a nonsense statement (and not to command, four subjects, P=0.049). CONCLUSIONS: Connected consciousness occured after intubation in 11% of young adults, with females at increased risk. Continuous exposure to anaesthesia between induction of anaesthesia and tracheal intubation should be considered to reduce the incidence of connected consciousness. Further research is required to understand sex-related differences in the risk of connected consciousness.

General Anesthesia: A Probe to Explore Consciousness.

General anesthesia reversibly alters consciousness, without shutting down the brain globally. Depending on the anesthetic agent and dose, it may produce different consciousness states including a complete absence of subjective experience (unconsciousness), a conscious experience without perception of the environment (disconnected consciousness, like during dreaming), or episodes of oriented consciousness with awareness of the environment (connected consciousness). Each consciousness state may potentially be followed by explicit or implicit memories after the procedure. In this respect, anesthesia can be considered as a proxy to explore consciousness. During the recent years, progress in the exploration of brain function has allowed a better understanding of the neural correlates of consciousness, and of their alterations during anesthesia. Several changes in functional and effective between-region brain connectivity, consciousness network topology, and spatio-temporal dynamics of between-region interactions have been evidenced during anesthesia. Despite a set of effects that are common to many anesthetic agents, it is still uneasy to draw a comprehensive picture of the precise cascades during general anesthesia. Several questions remain unsolved, including the exact identification of the neural substrate of consciousness and its components, the detection of specific consciousness states in unresponsive patients and their associated memory processes, the processing of sensory information during anesthesia, the pharmacodynamic interactions between anesthetic agents, the direction-dependent hysteresis phenomenon during the transitions between consciousness states, the mechanisms of cognitive alterations that follow an anesthetic procedure, the identification of an eventual unitary mechanism of anesthesia-induced alteration of consciousness, the relationship between network effects and the biochemical or sleep-wake cycle targets of anesthetic agents, as well as the vast between-studies variations in dose and administration mode, leading to difficulties in between-studies comparisons. In this narrative review, we draw the picture of the current state of knowledge in anesthesia-induced unconsciousness, from insights gathered on propofol, halogenated vapors, ketamine, dexmedetomidine, benzodiazepines and xenon. We also describe how anesthesia can help understanding consciousness, we develop the above-mentioned unresolved questions, and propose tracks for future research.

The Raw and Processed Electroencephalogram as a Monitoring and Diagnostic Tool.

In this narrative review, different aspects of electroencephalogram (EEG) monitoring during anesthesia are approached, with a special focus on cardiothoracic and vascular anesthesia, from the basic principles to more sophisticated diagnosis and monitoring utilities. The available processed EEG-derived indexes of the depth of the hypnotic component of anesthesia have well-defined limitations and usefulness. They prevent intraoperative awareness with recall in specific patient populations and under a specific anesthetic regimen. They prevent intraoperative overdose, and they shorten recovery times. They also help to avoid lengthy intraoperative periods of suppression activity, which are known to be deleterious in terms of outcome. Other than those available indexes, the huge amount of information contained in the EEG currently is being used only partially. Several other areas of interest regarding EEG during anesthesia have emerged in terms of anesthesia mechanisms elucidation, nociception monitoring, and diagnosis or prevention of brain insults.

Two different methods to assess sympathetic tone during general anesthesia lead to different findings.

Noxious stimulation influences the autonomic nervous system activity. Sympathetic tone monitoring is currently used to assess the adequacy of the balance between nociception and anti-nociception during general anesthesia. The Surgical Plethysmographic Index (SPI) and the EBMi software (Custos©) are commercial devices that use different algorithms to measure it. We aimed at determining whether those devices provide similar information during routine surgical procedures under general anesthesia. Data acquired during a previously published study in patients undergoing surgery under general anesthesia were retrospectively analyzed and passed through the EBMi software. The occurrence of EBMi alarms of increased sympathetic tone was compared to the occurrence of SPI values ≥ 60, a commonly recommended intraoperative SPI threshold. Trends in classical parameters of sympathetic tone during the 5 min preceding a SPI ≥ 60, namely blood pressure, heart rate, and plethysmographic pulse amplitude were assessed. SPI ≥ 60 episodes (n = 307) were more frequent than EBMi alerts (n = 240). Approximately 70% of EBMi alerts occurred during periods where the SPI was below 60. Among all episodes of SPI ≥ 60, absence of any EBMi alerts was much more frequent than the inverse. A majority, but not all SPI ≥ 60 episodes were consistently preceded by an increase in heart rate and/or a decrease in pulse amplitude. Blood pressure did not significantly change before SPI ≥ 60. Longer SPI ≥ 60 episodes were associated with lower anti-nociception anesthetic regimen. Different methods of sympathetic tone assessment during general anesthesia provide conflicting information. Prospective studies should be undertaken to clarify the clinical indications of both techniques.

Standardised noxious stimulation-guided individual adjustment of remifentanil target-controlled infusion to prevent haemodynamic responses to laryngoscopy and surgical incision: A randomised controlled trial.

BACKGROUND: The surgical plethysmographic index (SPI) is one of the available indexes of the nociception-antinociception (NAN) balance. Individually adjusting the NAN balance to prevent somatic responses to noxious stimulation remains a challenge. OBJECTIVES: To assess whether guiding remifentanil administration according to the SPI response to a calibrated noxious stimulus (NANCAL) can blunt the haemodynamic response to tracheal intubation and surgical incision. DESIGN: Randomised multicentre study. SETTING: Two Belgian university hospitals from January 2014 to April 2015. PATIENTS: After ethic review board approval and informed consent, 48 American Society of Anesthesiologists I or II adult patients scheduled for surgery under general anaesthesia were enrolled. INTERVENTIONS: Patients were randomly assigned to a SPI group, where remifentanil effect-site concentration was adjusted according to NANCAL, or a control group, where it was fixed at 4 ng ml. Propofol concentration was always adjusted to maintain the bispectral index close to 40. NANCAL consisted of a 100 Hz, 60 mA electrical tetanic stimulation during 30 s at the wrist before tracheal intubation and before surgical incision. MAIN OUTCOME MEASURES: The primary endpoint was the efficacy of the NANCAL-guided remifentanil administration to prevent the haemodynamic response to tracheal intubation and surgical incision. The secondary aim was to compare the ability of SPI, analgesia nociception index, pupil diameter and mean arterial pressure response to NANCAL to predict the haemodynamic response to tracheal intubation and surgical incision. RESULTS: Our SPI response to NANCAL-based correcting scheme for remifentanil administration was not superior to a fixed remifentanil concentration at blunting the haemodynamic response to tracheal intubation or surgical incision. Among all tested NAN balance indices, only mean arterial pressure had significant predictive ability with regard to the haemodynamic response to surgical incision. CONCLUSION: Further research is needed to define the best NANCAL stimulus and the best remifentanil correcting scheme to help individualised tailoring of antinociception for each specific subpopulation of surgical patients. TRIAL REGISTRATION: Clinicaltrials.gov NCT: 02884310; https://clinicaltrials.gov/ct2/show/NCT02884310.

Incidence of Connected Consciousness after Tracheal Intubation: A Prospective, International, Multicenter Cohort Study of the Isolated Forearm Technique.

BACKGROUND: The isolated forearm technique allows assessment of consciousness of the external world (connected consciousness) through a verbal command to move the hand (of a tourniquet-isolated arm) during intended general anesthesia. Previous isolated forearm technique data suggest that the incidence of connected consciousness may approach 37% after a noxious stimulus. The authors conducted an international, multicenter, pragmatic study to establish the incidence of isolated forearm technique responsiveness after intubation in routine practice. METHODS: Two hundred sixty adult patients were recruited at six sites into a prospective cohort study of the isolated forearm technique after intubation. Demographic, anesthetic, and intubation data, plus postoperative questionnaires, were collected. Univariate statistics, followed by bivariate logistic regression models for age plus variable, were conducted. RESULTS: The incidence of isolated forearm technique responsiveness after intubation was 4.6% (12/260); 5 of 12 responders reported pain through a second hand squeeze. Responders were younger than nonresponders (39 ± 17 vs. 51 ± 16 yr old; P = 0.01) with more frequent signs of sympathetic activation (50% vs. 2.4%; P = 0.03). No participant had explicit recall of intraoperative events when questioned after surgery (n = 253). Across groups, depth of anesthesia monitoring values showed a wide range; however, values were higher for responders before (54 ± 20 vs. 42 ± 14; P = 0.02) and after (52 ± 16 vs. 43 ± 16; P = 0.02) intubation. In patients not receiving total intravenous anesthesia, exposure to volatile anesthetics before intubation reduced the odds of responding (odds ratio, 0.2 [0.1 to 0.8]; P = 0.02) after adjustment for age. CONCLUSIONS: Intraoperative connected consciousness occurred frequently, although the rate is up to 10-times lower than anticipated. This should be considered a conservative estimate of intraoperative connected consciousness.