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Electroencephalographic (EEG) Patterns during the Awake State, General Anesthesia, and Sleep. Panel A shows the EEG patterns when the patient is awake, with eyes open (left) and the alpha rhythm (10 Hz) with eyes closed (right). Panel B shows the EEG patterns during the states of general anesthesia: paradoxical excitation, phases 1 and 2, burst suppression, and the isoelectric tracing. Panel C shows the EEG patterns during the stages of sleep: rapid-eye-movement (REM) sleep; stage 1 non-REM sleep; stage 2 non-REM sleep, and stage 3 non-REM (slow-wave) sleep. The EEG patterns during recovery from coma-coma, vegetative state, and minimally conscious state-resemble the patterns during general anesthesia, sleep, and the awake state. EEG tracings during sleep are from Watson et al. 5
Source publication
In the United States, nearly 60,000 patients per day receive general anesthesia for surgery.1 General anesthesia is a drug-induced, reversible condition that includes specific behavioral and physiological traits — unconsciousness, amnesia, analgesia, and akinesia — with concomitant stability of the autonomic, cardiovascular, respiratory, and thermo...
Contexts in source publication
Context 1
... induction, the patient has a normal, active EEG, with prominent alpha activity (10 Hz) when the eyes are closed (Fig. 1). Administration of a small dose of a hypnotic drug such as propofol, a barbiturate, or etomidate, all of which act on γ-aminobutyric acid type A (GABA A ) receptors, induces a state of sedation in which the patient is calm and easily arousable, with the eyes generally closed. 12 As the dose is slowly increased, the pa- tient may enter ...
Context 2
... for surgery, general anesthesia can functionally ap- proximate brain-stem death, 21 because patients are unconscious, have depressed brain-stem reflex- es, do not respond to nociceptive stimuli, have no apneic drive, and require cardiorespiratory and thermoregulatory support. 9 Four EEG patterns define the phases of the maintenance period (Fig. 1). Phase 1, a light state of general anesthesia, is characterized by a de- crease in EEG beta activity (13 to 30 Hz) and an increase in EEG alpha activity (8 to 12 Hz) and delta activity (0 to 4 Hz). 22 During phase 2, the intermediate state, beta activity decreases and al- pha and delta activity increases, with so-called anteriorization ...
Context 3
... spontaneous respirations and airway protection, even if there is no response to oral commands. The eyes may still not open spontaneously. As the patient emerges from general anesthesia, the EEG patterns proceed in approximately reverse order from phases 2 or 3 of the maintenance period to an active EEG that is consistent with a fully awake state (Fig. 1). Between extubation and dis-charge from the postanesthesia care unit, the pa- tient passes through a minimally conscious state. 27 Functional responses that are beyond a minimally conscious state must be evident before the pa- tient is discharged from the postanesthesia care unit. 27,28 The patient should be able to answer simple ...
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... EEG patterns and other features of general anesthesia generally differ from those of sleep (Fig. 1). The highly active state of the cortex dur- ing REM sleep is mediated by a cholinergic drive emanating from the basal forebrain and from the lateral dorsal and pedunculopontine tegmental nuclei to the cortex via the thalamus. 56 As dis- cussed below, paradoxical excitation under general anesthesia may represent GABA-mediated disin- ...
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... activation of pon- tomedullary networks, resulting in glycine-medi- ated inhibition of alpha motor neurons in the spinal cord, 66 whereas during paradoxical exci- tation, motor tone is preserved. 13 There is similarity between the EEG patterns seen in slow-wave sleep and those seen in phase 2 of the maintenance period of general anesthe- sia (Fig. 1). This period of general anesthesia is sufficiently deep to perform surgery. During sleep, the greatest decrease in pain perception occurs in the slow-wave stage. Arousal is possible during this stage, but it requires stronger stimulation than during other stages of sleep. 67 Slow-wave sleep has been shown to represent the switch of the ...
Context 6
... is increased to a dose beyond that which produces paradoxical excitation, its actions in the thalamocortical circuits lead to a coherent alpha oscillation between the thalamus and the ante- rior forebrain. 81 Finally, burst suppression is believed to be a strong, synchronized outflow of thalamic dis- charges to a widely unresponsive cortex 82 (Fig. 1). It is a deeper state of general anesthesia than is phase 2 of the maintenance period, which resem- bles the tonic bursting mode of the thalamus seen in slow-wave sleep. Bursts become more widely separated during burst suppression as the level of general anesthesia deepens. This suggests that a larger fraction of the cortex is inactive ...
Citations
... 5,6 Electroencephalographic (EEG) suppression is an accepted biomarker of deep anesthesia. 7 In an observational cohort study conducted in 727 patients undergoing major cardiac and thoracic surgery, every 5 minutes of EEG suppression was associated with a 5% increased adjusted odds of postoperative delirium. 8 The Electroencephalographic Guidance of Anesthesia to Alleviate Geriatric Syndromes (ENGAGES) trial did not find a decrease in delirium incidence with EEG guidance to minimize volatile anesthetic exposure and EEG suppression in older adults undergoing highrisk surgical procedures. ...
Importance
Intraoperative electroencephalogram (EEG) waveform suppression, suggesting excessive general anesthesia, has been associated with postoperative delirium.
Objective
To assess whether EEG-guided anesthesia decreases the incidence of delirium after cardiac surgery.
Design, Setting, and Participants
Randomized, parallel-group clinical trial of 1140 adults 60 years or older undergoing cardiac surgery at 4 Canadian hospitals. Recruitment was from December 2016 to February 2022, with follow-up until February 2023.
Interventions
Patients were randomized in a 1:1 ratio (stratified by hospital) to receive EEG-guided anesthesia (n = 567) or usual care (n = 573). Patients and those assessing outcomes were blinded to group assignment.
Main Outcomes and Measures
The primary outcome was delirium during postoperative days 1 through 5. Intraoperative measures included anesthetic concentration and EEG suppression time. Secondary outcomes included intensive care and hospital length of stay. Serious adverse events included intraoperative awareness, medical complications, and 30-day mortality.
Results
Of 1140 randomized patients (median [IQR] age, 70 [65-75] years; 282 [24.7%] women), 1131 (99.2%) were assessed for the primary outcome. Delirium during postoperative days 1 to 5 occurred in 102 of 562 patients (18.15%) in the EEG-guided group and 103 of 569 patients (18.10%) in the usual care group (difference, 0.05% [95% CI, −4.57% to 4.67%]). In the EEG-guided group compared with the usual care group, the median volatile anesthetic minimum alveolar concentration was 0.14 (95% CI, 0.15 to 0.13) lower (0.66 vs 0.80) and there was a 7.7-minute (95% CI, 10.6 to 4.7) decrease in the median total time spent with EEG suppression (4.0 vs 11.7 min). There were no significant differences between groups in median length of intensive care unit (difference, 0 days [95% CI, −0.31 to 0.31]) or hospital stay (difference, 0 days [95% CI, −0.94 to 0.94]). No patients reported intraoperative awareness. Medical complications occurred in 64 of 567 patients (11.3%) in the EEG-guided group and 73 of 573 (12.7%) in the usual care group. Thirty-day mortality occurred in 8 of 567 patients (1.4%) in the EEG-guided group and 13 of 573 (2.3%) in the usual care group.
Conclusions and Relevance
Among older adults undergoing cardiac surgery, EEG-guided anesthetic administration to minimize EEG suppression, compared with usual care, did not decrease the incidence of postoperative delirium. This finding does not support EEG-guided anesthesia for this indication.
Trial Registration
ClinicalTrials.gov Identifier: NCT02692300
... General anesthesia is a surgical procedure that involves a variety of drugs to induce unconsciousness, amnesia, analgesia, and muscle relaxation [1]. Nondepolarizing neuromuscular blocking drugs (NMBDs) are commonly used in general anesthesia during surgical procedures to provide muscle relaxation, facilitate endotracheal intubation, and improve surgical conditions [2]. ...
Understanding the intricate relationship between cancer clinicopathological features and anesthetics dosage is crucial for optimizing patient outcomes and safety during surgery. This retrospective study investigates this relationship in patients with non-small cell lung cancer (NSCLC) undergoing video-assisted thoracic surgery (VATS). A comprehensive analysis of medical records was undertaken for NSCLC patients who underwent VATS with intravenous compound inhalation general anesthesia. Patients were categorized based on histological, chemotherapy, radiotherapy, and epidural anesthesia factors. Statistical analysis was performed to compare the differences between the groups. The results revealed compelling insights. Specifically, patients with lung adenocarcinoma (LUAD) undergoing VATS exhibited higher dosages of rocuronium bromide and midazolam during general anesthesia, coupled with a shorter post-anesthesia care unit (PACU) stay compared to those with squamous cell carcinoma (sqCL). Furthermore, chemotherapy patients undergoing VATS demonstrated diminished requirements for phenylephrine and remifentanil in contrast to their non-chemotherapy counterparts. Similarly, radiotherapy patients undergoing VATS demonstrated a decreased necessity for rocuronium bromide compared to non-radiotherapy patients. Notably, patients who received epidural anesthesia in combination with general anesthesia manifested reduced hydromorphone requirements and prolonged hospital stays compared to those subjected to general anesthesia alone. In conclusion, the findings from this study indicate several important observations in diverse patient groups undergoing VATS. The higher dosages of rocuronium bromide and midazolam in LUAD patients point to potential differences in drug requirements among varying lung cancer types. Additionally, the observed shorter PACU stay in LUAD patients suggests a potentially expedited recovery process. The reduced anesthetic requirements of phenylephrine and remifentanilin chemotherapy patients indicate distinct responses to anesthesia and pain management. Radiotherapy patients requiring lower doses of rocuronium bromide imply a potential impact of prior radiotherapy on muscle relaxation. Finally, the combination of epidural anesthesia with general anesthesia resulted in reduced hydromorphone requirements and longer hospital stays, suggesting the potential benefits of this combined approach in terms of pain management and postoperative recovery. These findings highlight the importance of tailoring anesthesia strategies for specific patient populations to optimize outcomes in VATS procedures.
... Anesthesia could be reversibly induced by the anesthetic agents and makes the brain and body condition into the following specific behavioral and physiological traits (Brown et al., 2010). 1. Analgesia: Animals do not perceive pain. ...
Brain research has progressed with anesthetized animal experiments for a long time. Recent progress in research techniques allows us to measure neuronal activity in awake animals combined with behavioral tasks. The trends became more prominent in the last decade. This new research style triggers the paradigm shift in the research of brain science, and new insights into brain function have been revealed. It is reasonable to consider that awake animal experiments are more ideal for understanding naturalistic brain function than anesthetized ones. However, the anesthetized animal experiment still has advantages in some experiments. To take advantage of the anesthetized animal experiments, it is important to understand the mechanism of anesthesia and carefully handle the obtained data. In this minireview, we will shortly summarize the molecular mechanism of anesthesia in animal experiments, a recent understanding of the neuronal activities in a sensory system in the anesthetized animal brain, and consider the advantages and disadvantages of the anesthetized and awake animal experiments. This discussion will help us to use both research conditions in the proper manner.
... These results are corroborated by previous analyses of these data [59] that indicated a rapid state change in which local network interactions were preserve but spatially distant network interactions were disrupted during anesthesia. Previous studies have shown that propofol acts by enhancing GABAergic circuits whose recurrent dynamics contribute to inducing synchronized slow-wave oscillatory activity [59][60][61][62][63]. Ensemble spiking history regressors likely accounted for these recurrent dynamics in the history-dependent model so that no exogenous effects were detected. ...
Central in the study of population codes, coordinated ensemble spiking activity is widely observable in neural recordings with hypothesized roles in robust stimulus representation, interareal communication, and learning and memory formation. Model-free measures of synchrony characterize coherent pairwise activity but not higher-order interactions, a limitation transcended by statistical models of ensemble spiking activity. However, existing model-based analyses often impose assumptions about the relevance of higher-order interactions and require repeated trials to characterize dynamics in the correlational structure of ensemble activity. To address these shortcomings, we propose an adaptive greedy filtering algorithm based on a discretized mark point-process model of ensemble spiking and a corresponding statistical inference framework to identify significant higher-order coordination. In the course of developing a precise statistical test, we show that confidence intervals can be constructed for greedily estimated parameters. We demonstrate the utility of our proposed methods on simulated neuronal assemblies. Applied to multi-electrode recordings from human and rat cortical assemblies, our proposed methods provide new insights into the dynamics underlying localized population activity during transitions between brain states.
... The most used volatile inhalation anesthetics include nitrous oxide, desflurane, isoflurane, halothane, enflurane, among others. Halothane is frequently used as an anesthetic agent in pediatrics due to its non-irritant nature and its ability to induce anesthesia gently and rapidly in children [13]. ...
Anesthesia plays a crucial role in pediatric laparoscopic procedures. It highlights the unique challenges posed by laparoscopic surgery in young children and newborns, and the need for specialized care in the selection and administration of anesthetics. The text further investigates the physiological impacts of laparoscopic surgery, such as hemodynamic changes due to increased intra-abdominal pressure, and potential complications arising from prolonged CO2 absorption. The need for a pediatric anesthesiologist to be trained to perform good anesthetic techniques in these procedures, such as increasing the ventilatory minute volume to counteract lethal effects, is also analyzed.
... They safely induce reversible brain states conducive to achieving a state required to perform surgical or invasive medical procedures. GAAs induce unconsciousness by altering neurotransmission in multiple regions of the cerebral cortex, brainstem, and thalamus (Brown et al., 2010). Targets of GAAs include receptors such as those for γ-aminobutyric acid (GABA) and N-methyl-D-aspartate (NMDA), ion channels, enzymes, and other proteins. ...
General anesthetic agents can impact brain function through interactions with neurons and their effects on glial cells. Oligodendrocytes perform essential roles in the central nervous system, including myelin sheath formation, axonal metabolism, and neuroplasticity regulation. They are particularly vulnerable to the effects of general anesthetic agents resulting in impaired proliferation, differentiation, and apoptosis. Neurologists are increasingly interested in the effects of general anesthetic agents on oligodendrocytes. These agents not only act on the surface receptors of oligodendrocytes to elicit neuroinflammation through modulation of signaling pathways, but also disrupt metabolic processes and alter the expression of genes involved in oligodendrocyte development and function. In this review, we summarize the effects of general anesthetic agents on oligodendrocytes. We anticipate that future research will continue to explore these effects and develop strategies to decrease the incidence of adverse reactions associated with the use of general anesthetic agents.
... In fact, group ICA extracts stable components across subjects thanks to the data reduction steps before the ICA decomposition stage (Calhoun et al., 2001) without the need for any additional assumption. In addition, by knowing that during the prolonged down states in the deepest state of anesthesia, neuronal activity was minimal Brown et al., 2010), we used this as a reference to construct the thresholds for each component time course. This allowed us to identify the data points where components significantly contributed to the overall fluorescence signal. ...
Large-scale cortical dynamics play a crucial role in many cognitive functions such as goal-directed behaviors, motor learning and sensory processing. It is well established that brain states including wakefulness, sleep, and anesthesia modulate neuronal firing and synchronization both within and across different brain regions. However, how the brain state affects cortical activity at the mesoscale level is less understood. This work aimed to identify the cortical regions engaged in different brain states. To this end, we employed group ICA (Independent Component Analysis) to wide-field imaging recordings of cortical activity in mice during different anesthesia levels and the awake state. Thanks to this approach we identified independent components (ICs) representing elements of the cortical networks that are common across subjects under decreasing levels of anesthesia toward the awake state. We found that ICs related to the retrosplenial cortices exhibited a pronounced dependence on brain state, being most prevalent in deeper anesthesia levels and diminishing during the transition to the awake state. Analyzing the occurrence of the ICs we found that activity in deeper anesthesia states was characterized by a strong correlation between the retrosplenial components and this correlation decreases when transitioning toward wakefulness. Overall these results indicate that during deeper anesthesia states coactivation of the posterior-medial cortices is predominant over other connectivity patterns, whereas a richer repertoire of dynamics is expressed in lighter anesthesia levels and the awake state.
... A widely established method to evaluate the electrophysiological effects of anesthetics on the brain is the electroencephalogram (EEG), which has first been described in 1929 [6][7][8]. As it is a non-invasive technique, it can easily be applied and allows the analysis of cortical and to a limited degree also of subcortical activities [9]. ...
... A comparison of VC recordings at baseline versus anesthesia maintenances revealed a significant decrease in the theta (5.9-8 Hz), alpha (8)(9)(10)(11)(12), and low-beta band (12-14.2 Hz) for sevoflurane. ...
... The transient phenomenon is called paradoxical excitation and is accompanied by changes in the EEG [48]. These changes are predominantly characterized by an increase of the beta band as well as a decrease of alpha band and theta band power [49], primarily induced by GABAergic drugs [8]. In the present experiments, analogue changes were found, previously exclusively described in humans [50]. ...
The exact mechanisms and the neural circuits involved in anesthesia induced unconsciousness are still not fully understood. To elucidate them valid animal models are necessary. Since the most commonly used species in neuroscience are mice, we established a murine model for commonly used anesthetics/sedatives and evaluated the epidural electroencephalographic (EEG) patterns during slow anesthesia induction and emergence. Forty-four mice underwent surgery in which we inserted a central venous catheter and implanted nine intracranial electrodes above the prefrontal, motor, sensory, and visual cortex. After at least one week of recovery, mice were anesthetized either by inhalational sevoflurane or intravenous propofol, ketamine, or dexmedetomidine. We evaluated the loss and return of righting reflex (LORR/RORR) and recorded the electrocorticogram. For spectral analysis we focused on the prefrontal and visual cortex. In addition to analyzing the power spectral density at specific time points we evaluated the changes in the spectral power distribution longitudinally. The median time to LORR after start anesthesia ranged from 1080 [1st quartile: 960; 3rd quartile: 1080]s under sevoflurane anesthesia to 1541 [1455; 1890]s with ketamine. Around LORR sevoflurane as well as propofol induced a decrease in the theta/alpha band and an increase in the beta/gamma band. Dexmedetomidine infusion resulted in a shift towards lower frequencies with an increase in the delta range. Ketamine induced stronger activity in the higher frequencies. Our results showed substance-specific changes in EEG patterns during slow anesthesia induction. These patterns were partially identical to previous observations in humans, but also included significant differences, especially in the low frequencies. Our study emphasizes strengths and limitations of murine models in neuroscience and provides an important basis for future studies investigating complex neurophysiological mechanisms.
Supplementary Information
The online version contains supplementary material available at 10.1186/s12871-024-02552-3.
... General anesthesia is a drug-induced state of unconsciousness that makes it possible to conduct more than 200 million major surgical procedures around the world each year [1,2]. While general anesthesia can be induced by a variety of pharmacologically diverse agents, there are currently no drugs available to reverse this state in humans. ...
... [8][9][10] Propofol, like other hypnotic agents, achieves unconsciousness by "altering neurotransmission in multiple regions in the cerebral cortex, brainstem and thalamus". [11] Administration of a small dose of a hypnotic drug such as Propofol or etomidate, which act on γ-aminobutyric acid type A (GABA A ) receptors, induces a state of sedation in which the patient is calm and easily aroused, with eyes usually closed. [12] The currently available formulation of propofol in the market is a lipid emulsion that has side effects such as pain on injection site, serious allergic reactions, and support of microbial growth. ...
This study was designed to synthesize hybrid molecules starting from 2,6‐diisopropyl aniline (1), which is similar to Propofol (2,6‐diisopropyl phenol), by increasing its biological activity with other heterocycles and to determine the anesthetic activity of the obtained compounds. For this purpose, commercially available 2,6‐diisopropylaniline (1) was used as a starting compound. Then, ester (2), hydrazide (3), carbothioamide (5, 6) and Schiff bases derivatives (4 a–f) were synthesized, respectively. To achieve the etomidate‐like target compound 8, compound 7 containing chloroacetamide group was firstly synthesized from starting compound 1, and this compound reacted with ethyl‐1H‐imidazole‐5‐carboxylate. The structures of the newyl synthesized 12 compounds were characterized and confirmed by FT‐IR, MALDI‐TOF/MS, ¹H NMR, ¹³C NMR.
Within the scope of in silico study, ligand binding status of all compounds on the GABAA receptor was revealed. Molecular docking studies of them with GABAA found out that the interaction modes, including van der Waals interactions, hydrogen bonds, and pi‐pi interactions, are similar to that of the cocrystalline ligand Propofol. For the compounds 1, 2, 3, 4 d, 5, 7 have micromolar (μM) level, for the compounds 4 a, 4 b, 4 c, 4 e, 4 f, 6 and 8 have nanomolar (nM) level of inhibition has been estimated. When all data such as active localization, interacting residues, bond types formed, estimated Ki values, docking scores are evaluated together, compounds 1, 2, 3 and 7 which can be considered as synthesis starting or intermediate material, may be less effective.
On the other hand the anticancer activities of the synthesized compounds were investigated against A549 (non‐small cell lung carcinoma) and BEAS‐2B cell line (normal bronchial epithelial) cell lines using Resazurin cell viability assay. It has been revealed that the compounds 4, 5, 6 and 8 may be more active in terms of anesthetic activity, whereas only compound 6 showed anti‐cancer activity.
