Five commercial 'depth of anaesthesia' monitors provide discordant clinical recommendations in response to identical emergence-like EEG signals.

BACKGROUND: 'Depth of anaesthesia' monitors claim to measure hypnotic depth during general anaesthesia from the EEG, and clinicians could reasonably expect agreement between monitors if presented with the same EEG signal. We took 52 EEG signals showing intraoperative patterns of diminished anaesthesia, similar to those that occur during emergence (after surgery) and subjected them to analysis by five commercially available monitors. METHODS: We compared five monitors (BIS, Entropy-SE, Narcotrend, qCON, and Sedline) to see if index values remained within, or moved out of, each monitors' recommended index range for general anaesthesia for at least 2 min during a period of supposed lighter anaesthesia, as observed by changes in the EEG spectrogram obtained in a previous study. RESULTS: Of the 52 cases, 27 (52%) had at least one monitor warning of potentially inadequate hypnosis (index above range) and 16 of the 52 cases (31%) had at least one monitor signifying excessive hypnotic depth (index below clinical range). Of the 52 cases, only 16 (31%) showed concordance between all five monitors. Nineteen cases (36%) had one monitor discordant compared with the remaining four, and 17 cases (33%) had two monitors in disagreement with the remaining three. CONCLUSIONS: Many clinical providers still rely on index values and manufacturer's recommended ranges for titration decision making. That two-thirds of cases showed discordant recommendations given identical EEG data, and that one-third signified excessive hypnotic depth where the EEG would suggest a lighter hypnotic state, emphasizes the importance of personalised EEG interpretation as an essential clinical skill.

Breathe-squeeze: pharmacodynamics of a stimulus-free behavioural paradigm to track conscious states during sedation☆.

BACKGROUND: Conscious states are typically inferred through responses to auditory tasks and noxious stimulation. We report the use of a stimulus-free behavioural paradigm to track state transitions in responsiveness during dexmedetomidine sedation. We hypothesised that estimated dexmedetomidine effect-site (Ce) concentrations would be higher at loss of responsiveness (LOR) compared with return of responsiveness (ROR), and both would be lower than comparable studies that used stimulus-based assessments. METHODS: Closed-Loop Acoustic Stimulation during Sedation with Dexmedetomidine data were analysed for secondary analysis. Fourteen healthy volunteers were asked to perform the breathe-squeeze task of gripping a dynamometer when inspiring and releasing it when expiring. LOR was defined as five inspirations without accompanied squeezes; ROR was defined as the return of five inspirations accompanied by squeezes. Brain states were monitored using 64-channel EEG. Dexmedetomidine was administered as a target-controlled infusion, with Ce estimated from a pharmacokinetic model. RESULTS: Counter to our hypothesis, mean estimated dexmedetomidine Ce was lower at LOR (0.92 ng ml-1; 95% confidence interval: 0.69-1.15) than at ROR (1.43 ng ml-1; 95% confidence interval: 1.27-1.58) (paired t-test; P=0.002). LOR was characterised by progressively increasing fronto-occipital EEG power in the 0.5-8 Hz band and loss of occipital alpha (8-12 Hz) and global beta (16-30 Hz) power. These EEG changes reverted at ROR. CONCLUSIONS: The breathe-squeeze task can effectively track changes in responsiveness during sedation without external stimuli and might be more sensitive to state changes than stimulus-based tasks. It should be considered when perturbation of brain states is undesirable. CLINICAL TRIAL REGISTRATION: NCT04206059.

A Pilot Investigation Evaluating Relative Changes in Fronto-Occipital Alpha and Beta Spectral Power as Measurement of Anesthesia Hypnotic Depth.

BACKGROUND: Other than clinical observation of a patient's vegetative response to nociception, monitoring the hypnotic component of general anesthesia (GA) and unconsciousness relies on electroencephalography (EEG)-based indices. These indices exclusively based on frontal EEG activity neglect an important observation. One of the main hallmarks of transitions from wakefulness to GA is a shift in alpha oscillations (7.5-12.5 Hz activity) from occipital brain regions toward anterior brain regions ("alpha anteriorization"). Monitoring the degree of this alpha anteriorization may help to guide induction and maintenance of hypnotic depth and prevent intraoperative awareness. However, the occipital region of the brain is completely disregarded and occipital alpha as characteristic of wakefulness and its posterior-to-anterior shift during induction are missed. Here, we propose an application of Narcotrend's reduced power alpha beta (RPAB) index, originally developed to monitor differences in hemispheric perfusion, for determining the ratio of alpha and beta activity in the anterior-posterior axis. METHODS: Perioperative EEG data of 32 patients undergoing GA in the ophthalmic surgery department of Bern University Hospital were retrospectively analyzed. EEG was recorded with the Narcotrend® monitor using a frontal (Fp1-Fp2) and a posterior (T9-Oz) bipolar derivation with reference electrode over A2. The RPAB index was computed between both bipolar signals, defining the fronto-occipital RPAB (FO-RPAB). FO-RPAB was analyzed during wakefulness, GA maintenance, and emergence, as well as before and after the intraoperative administration of a ketamine bolus. FO-RPAB was compared with a classical quantitative EEG measure-the spectral edge frequency 95% (SEF-95). RESULTS: A significant shift of the FO-RPAB was observed during both induction of and emergence from GA ( P < .001). Interestingly, the additional administration of ketamine during GA did not lead to a significant change in FO-RPAB ( P = 0.81). In contrast, a significant increase in the SEF-95 in the frontal channel was observed during the 10-minute period after ketamine administration ( P < .001). CONCLUSIONS: FO-RPAB appears to qualify as a marker of unconsciousness, reflecting physiological fronto-occipital activity differences during GA. In contrast to frontal SEF-95, it is not disturbed by additional administration of ketamine for analgesia.

Association Between Risk of Stroke and Delirium After Cardiac Surgery and a New Electroencephalogram Index of Interhemispheric Similarity.

OBJECTIVES: Neurologic complications after surgery (stroke, delirium) remain a major concern despite advancements in surgical and anesthetic techniques. The authors aimed to evaluate whether a novel index of interhemispheric similarity, the lateral interconnection ratio (LIR), between 2 prefrontal electroencephalogram (EEG) channels could be associated with stroke and delirium following cardiac surgery. DESIGN: Retrospective observational study. SETTING: Single university hospital. PARTICIPANTS: A total of 803 adult patients without documentation of a previous stroke, who underwent cardiac surgery with cardiopulmonary bypass (CPB) between July 2016 and January 2018. INTERVENTIONS: The LIR index was calculated retrospectively from the patients' EEG database. MEASUREMENTS AND MAIN RESULTS: LIR was analyzed intraoperatively every 10 seconds and compared among patients with postoperative stroke, patients with delirium, and patients without documented neurologic complications, during 5 key periods, each lasting10 minutes: (1) surgery start, (2) before CPB, (3) on CPB, (4) after CPB, and (5) surgery end. After cardiac surgery, 31 patients suffered from stroke; 48 patients were diagnosed with delirium; and 724 had no documented neurologic complications. Patients with stroke demonstrated a decrease in LIR index between the start of surgery and the postbypass period of 0.08 (0.01, 0.36 [21]; median and [interquartile range {IQR}]; valid EEG samples); whereas there was no similar decrease in the no-dysfunction group (-0.04 [-0.13, 0.04; {551}], p < 0.0001). Patients with delirium showed a decrease in LIR index between the start of surgery and the end of the surgery by 0.15 (0.02, 0.30 [12]), compared with no such decrease in the no-dysfunction group (-0.02 [-0.12, 0.08 {376}], p ≈ 0.001). CONCLUSIONS: After improvement of SNR, it might be of value to further study the index decrease as an indication for risk for brain injury after surgery. The timing of decrease (after CPB or end of surgery) may provide hints regarding the injury pathophysiology and its onset.

The nuts and bolts of multimodal anaesthesia in the 21st century: a primer for clinicians.

PURPOSE OF REVIEW: This review article explores the application of multimodal anaesthesia in general anaesthesia, particularly in conjunction with locoregional anaesthesia, specifically focusing on the importance of EEG monitoring. We provide an evidence-based guide for implementing multimodal anaesthesia, encompassing drug combinations, dosages, and EEG monitoring techniques, to ensure reliable intraoperative anaesthesia while minimizing adverse effects and improving patient outcomes. RECENT FINDINGS: Opioid-free and multimodal general anaesthesia have significantly reduced opioid addiction and chronic postoperative pain. However, the evidence supporting the effectiveness of these approaches is limited. This review attempts to integrate research from broader neuroscientific fields to generate new clinical hypotheses. It discusses the correlation between high-dose intraoperative opioids and increased postoperative opioid consumption and their impact on pain indices and readmission rates. Additionally, it explores the relationship between multimodal anaesthesia and pain processing models and investigates the potential effects of nonpharmacological interventions on preoperative anxiety and postoperative pain. SUMMARY: The integration of EEG monitoring is crucial for guiding adequate multimodal anaesthesia and preventing excessive anaesthesia dosing. Furthermore, the review investigates the impact of combining regional and opioid-sparing general anaesthesia on perioperative EEG readings and anaesthetic depth. The findings have significant implications for clinical practice in optimizing multimodal anaesthesia techniques (Supplementary Digital Content 1: Video Abstract, http://links.lww.com/COAN/A96 ).

Consciousness and the outside world: is there anyone listening?

Sedated patients have graded levels of consciousness and perceptual connection with the outside world. Disconnection is associated with widespread changes in the electroencephalogram, whereas full unconsciousness is linked with decreased activity specifically in the deep midline regions of the brain. These findings can be interpreted within the predictive coding model of consciousness as differences in model generation vs discrepancy detection. Anaesthetists should be cognisant that apparently unresponsive patients might still have some ongoing partially disconnected consciousness activity.

The First Derivative of the Electroencephalogram Facilitates Tracking of Electroencephalographic Alpha Band Activity During General Anesthesia.

BACKGROUND: Intraoperative neuromonitoring can help to navigate anesthesia. Pronounced alpha oscillations in the frontal electroencephalogram (EEG) appear to predict favorable perioperative neurocognitive outcomes and may also provide a measure of intraoperative antinociception. Monitoring the presence and strength of these alpha oscillations can be challenging, especially in elderly patients, because the EEG in these patients may be dominated by oscillations in other frequencies. Hence, the information regarding alpha oscillatory activity may be hidden and hard to visualize on a screen. Therefore, we developed an effective approach to improve the detection and presentation of alpha activity in the perioperative setting. METHODS: We analyzed EEG records of 180 patients with a median age of 60 years (range, 18-90 years) undergoing noncardiac, nonneurologic surgery under general anesthesia with propofol induction and sevoflurane maintenance. We calculated the power spectral density (PSD) for the unprocessed EEG as well as for the time-discrete first derivative of the EEG (diffPSD) from 10-second epochs. Based on these data, we estimated the power-law coefficient κ of the PSD and diffPSD, as the EEG coarsely follows a 1/fκ distribution when displayed in double logarithmic coordinates. In addition, we calculated the alpha (7.8-12.1 Hz) to delta (0.4-4.3 Hz) ratio from the PSD as well as diffPSD. RESULTS: The median κ was 0.899 [first and third quartile: 0.786, 0.986] for the unaltered PSD, and κ = -0.092 [-0.202, -0.013] for the diffPSD, corresponding to an almost horizontal PSD of the differentiated EEG. The alpha-to-delta ratio of the diffPSD was strongly increased (median ratio = -8.0 dB [-10.5, -4.7 dB] for the unaltered PSD versus 30.1 dB [26.1, 33.8 dB] for the diffPSD). A strong narrowband oscillatory alpha power component (>20% of total alpha power) was detected in 23% using PSD, but in 96% of the diffPSD. CONCLUSIONS: We demonstrated that the calculation of the diffPSD from the time-discrete derivative of the intraoperative frontal EEG is a straightforward approach to improve the detection of alpha activity by eliminating the broadband background noise. This improvement in alpha peak detection and visualization could facilitate the guidance of general anesthesia and improve patient outcome.

Age, minimum alveolar concentration and choice of depth of sedation monitor: examining the paradox of age when using the Narcotrend monitor: A secondary analysis of an observational study.

BACKGROUND: With an ageing global population, it is important to individualise titration of anaesthetics according to age and by measuring their effect on the brain. A recent study reported that during general surgery, the given concentration of volatile anaesthetics, expressed as a fraction of the minimum alveolar concentration (MAC fraction), decreases by around only 3% per age-decade, which is less than the 6% expected from age-adjusted MAC. Paradoxically, despite the excessive dosing, Bispectral index (BIS) values also increased. OBJECTIVE: We planned to investigate the paradox of age when using the Narcotrend depth of anaesthesia monitor. DESIGN: Secondary analyses of a prospective observational study. SETTING: Tertiary hospital in Switzerland, recordings took place during 2016 and 2017. PATIENTS: One thousand and seventy-two patients undergoing cardiac surgery entered the study, and 909 with noise-free recordings and isoflurane anaesthesia were included in this analysis. INTERVENTION: We calculated mean end-tidal MAC fraction and mean index value of the Narcotrend depth of sedation monitor used in the study during the prebypass period. Statistical associations were modelled using linear regression, local weighted regression (LOESS) and a generalised additive model (GAM). MAIN OUTCOME MEASURES: Primary endpoints in this study were the change in end-tidal MAC fraction and mean Narcotrend index values, both measured per age-decade. RESULTS: We observed a linear decrease in end-tidal MAC fraction of 3.2% per age-decade [95% confidence interval (CI) -3.97% to -2.38%, P < 0.001], consistent with previous findings. In contrast to the BIS, mean Narcotrend index values decreased with age at 3.0 index points per age-decade (95% CI, -3.55 points to -2.36 points, P < 0.001), a direction of change commensurate with the increasing age-adjusted MAC fraction with patient age. These relationships were consistent regardless of whether age-adjusted MAC was displayed on the anaesthetic machine. CONCLUSIONS: We caution that the 'paradox of age' may in part depend on the choice of depth of sedation monitor. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02976584.

Effects of noxious stimulation on the electroencephalogram during general anaesthesia: a narrative review and approach to analgesic titration.

Electroencephalographic (EEG) activity is used to monitor the neurophysiology of the brain, which is a target organ of general anaesthesia. Besides its use in evaluating hypnotic states, neurophysiologic reactions to noxious stimulation can also be observed in the EEG. Recognising and understanding these responses could help optimise intraoperative analgesic management. This review describes three types of changes in the EEG induced by noxious stimulation when the patient is under general anaesthesia: (1) beta arousal, (2) (paradoxical) delta arousal, and (3) alpha dropout. Beta arousal is an increase in EEG power in the beta-frequency band (12-25 Hz) in response to noxious stimulation, especially at lower doses of anaesthesia drugs in the absence of opioids. It is usually indicative of a cortical depolarisation and increased cortical activity. At higher concentrations of anaesthetic drug, and with insufficient opioids, delta arousal (increased power in the delta band [0.5-4 Hz]) and alpha dropout (decreased alpha power [8-12 Hz]) are associated with noxious stimuli. The mechanisms of delta arousal are not well understood, but the midbrain reticular formation seems to play a role. Alpha dropout may indicate a return of thalamocortical communication, from an idling mode to an operational mode. Each of these EEG changes reflect an incomplete modulation of pain signals and can be mitigated by administration of opioid or the use of regional anaesthesia techniques. Future studies should evaluate whether titrating analgesic drugs in response to these EEG signals reduces postoperative pain and influences other postoperative outcomes, including the potential development of chronic pain.

Spectral and Entropic Features Are Altered by Age in the Electroencephalogram in Patients under Sevoflurane Anesthesia.

BACKGROUND: Preexisting factors such as age and cognitive performance can influence the electroencephalogram (EEG) during general anesthesia. Specifically, spectral EEG power is lower in elderly, compared to younger, subjects. Here, the authors investigate age-related changes in EEG architecture in patients undergoing general anesthesia through a detailed examination of spectral and entropic measures. METHODS: The authors retrospectively studied 180 frontal EEG recordings from patients undergoing general anesthesia, induced with propofol/fentanyl and maintained by sevoflurane at the Waikato Hospital in Hamilton, New Zealand. The authors calculated power spectral density and normalized power spectral density, the entropic measures approximate and permutation entropy, as well as the beta ratio and spectral entropy as exemplary parameters used in current monitoring systems from segments of EEG obtained before the onset of surgery (i.e., with no noxious stimulation). RESULTS: The oldest quartile of patients had significantly lower 1/f characteristics (P < 0.001; area under the receiver operating characteristics curve, 0.84 [0.76 0.92]), indicative of a more uniform distribution of spectral power. Analysis of the normalized power spectral density revealed no significant impact of age on relative alpha (P = 0.693; area under the receiver operating characteristics curve, 0.52 [0.41 0.63]) and a significant but weak effect on relative beta power (P = 0.041; area under the receiver operating characteristics curve, 0.62 [0.52 0.73]). Using entropic parameters, the authors found a significant age-related change toward a more irregular and unpredictable EEG (permutation entropy: P < 0.001, area under the receiver operating characteristics curve, 0.81 [0.71 0.90]; approximate entropy: P < 0.001; area under the receiver operating characteristics curve, 0.76 [0.66 0.85]). With approximate entropy, the authors could also detect an age-induced change in alpha-band activity (P = 0.002; area under the receiver operating characteristics curve, 0.69 [0.60 78]). CONCLUSIONS: Like the sleep literature, spectral and entropic EEG features under general anesthesia change with age revealing a shift toward a faster, more irregular, oscillatory composition of the EEG in older patients. Age-related changes in neurophysiological activity may underlie these findings however the contribution of age-related changes in filtering properties or the signal to noise ratio must also be considered. Regardless, most current EEG technology used to guide anesthetic management focus on spectral features, and improvements to these devices might involve integration of entropic features of the raw EEG.

Comorbidity-dependent changes in alpha and broadband electroencephalogram power during general anaesthesia for cardiac surgery.

BACKGROUND: Age and comorbidities are reported to induce neurobiological transformations in the brain. Whilst the influence of ageing on anaesthesia-induced electroencephalogram (EEG) changes has been investigated, the effect of comorbidities has not yet been explored. We hypothesised that certain diseases significantly affect frontal EEG alpha and broadband power in cardiac surgical patients. METHODS: We analysed the frontal EEGs of 589 patients undergoing isoflurane general anaesthesia from a prospective observational study. We used multi- and uni-variable regression to analyse the relationships between comorbidities and age as independent with peak and oscillatory alpha, and broadband power as dependent variables. A score of comorbidities and minimum alveolar concentration (MAC) was built to interrogate the combined effect of age and score on alpha and broadband power. RESULTS: At the univariable level, many comorbidities were associated with lower EEG alpha or broadband power. Multivariable regression indicated the independent association of numerous comorbidities and MAC with peak alpha (R2=0.19) and broadband power (R2=0.31). The association with peak alpha power is markedly reduced when the underlying broadband effect is subtracted (R2=0.09). Broadband measures themselves are more strongly correlated with comorbidities and MAC (R2=0.31) than age (R2=0.15). CONCLUSIONS: Comorbidities and age are independently associated with decreasing frontal EEG alpha and broadband power during general anaesthesia. For alpha power, the association is highly dependent on the underlying broadband effect. These findings might have significant clinical consequences for automated computation for depth of anaesthesia in comorbid patients, because misclassification might pose the risk of under- or over-dosing of anaesthetics. CLINICAL TRIAL REGISTRATION: NCT02976584.

Frontal electroencephalogram reveals emergence-like brain activity occurring during transition periods in cardiac surgery.

BACKGROUND: Cardiac surgery has one of the highest incidences of intraoperative awareness. The periods of initiation and discontinuation of cardiopulmonary bypass could be high-risk periods. Certain frontal EEG patterns might plausibly occur with unintended intraoperative awareness. This study sought to quantify the incidence of these pre-specified patterns during cardiac surgery. METHODS: Two-channel bihemispheric frontal EEG was recorded in 1072 patients undergoing cardiac surgery as part of a prospective observational study. Spectrograms were created, and mean theta (4-7 Hz) power and peak alpha (7-17 Hz) frequency were measured in patients under general anaesthesia with isoflurane. Emergence-like EEG activity in the spectrogram during surgery was classified as an alpha peak frequency increase by 2 Hz or more, and a theta power decrease by 5 dB or more in comparison with the median pre-bypass values. RESULTS: Data from 1002 patients were available for analysis. Fifty-five of those patients (5.5%) showed emergence-like EEG activity at least once during surgery with a median duration of 13.2 min. These patients were younger (median age, 59 vs 67 yr; P<0.001) and the median end-tidal isoflurane concentration before cardiopulmonary bypass was higher (0.82 vs 0.75 minimum alveolar concentration [MAC]; P=0.013). There was no significant difference between those with or without emergence-like EEG activity in sex, lowest core temperature, or duration of surgery. Forty-six of these EEG changes (84%) occurred within a 1 h time window centred on separation from cardiopulmonary bypass. CONCLUSION: The findings of this study suggest that approximately one in 20 patients undergoing cardiac surgery with a volatile anaesthetic agent have a sustained EEG pattern while surgery is ongoing that is often seen with emergence from general anaesthesia. Monitoring the frontal EEG during cardiopulmonary bypass may identify these events and potentially reduce the incidence of unintended awareness. CLINICAL TRIAL REGISTRATION: NCT02976584.

Continuing professional development module : An updated introduction to electroencephalogram-based brain monitoring during intended general anesthesia.

The electroencephalogram (EEG) provides a reliable reflection of the brain's electrical state, so it can reassure us that the anesthetic agents are actually reaching the patient's brain, and are having the desired effect. In most patients, the EEG changes somewhat predictably in response to propofol and volatile agents, so a frontal EEG channel can guide avoidance of insufficient and excessive administration of general anesthesia. Persistent alpha-spindles (around 10 Hz) phase-amplitude coupled with slow delta waves (around 1 Hz) are commonly seen during an "appropriate hypnotic state of general anesthesia". Such patterns can be appreciated from the EEG waveform or from the spectrogram (a colour-coded display of how the power in the various EEG frequencies changes with time). Nevertheless, there are exceptions to this. For example, administration of ketamine and nitrous oxide is generally not associated with the aforementioned alpha-spindle coupled with delta wave pattern. Also, some patients, including older adults and those with neurodegenerative disorders, are less predisposed to generate a strong electroencephalographic "alpha-spindle" pattern during general anesthesia. There might also be some rare instances when the frontal EEG shows a pattern suggestive of general anesthesia, while the patient has some awareness and is able to follow simple commands, albeit this is typically without obvious distress or memory formation. Thus, the frontal EEG alone, as currently analyzed, is an imperfect but clinically useful mirror, and more scientific insights will be needed before we can claim to have a reliable readout of brain "function" during general anesthesia.

RéSUMé: L'électroencéphalogramme (EEG) procure une image fiable de l'état électrique du cerveau, de telle sorte qu'il peut nous rassurer que les agents anesthésiques atteignent bien le cerveau du patient et ont l'effet désiré. Chez la plupart des patients, le tracé de l'EEG change de façon relativement prévisible en réponse au propofol et aux agents volatils; ainsi, une analyse d'EEG frontal peut prévenir l'administration insuffisante ou excessive d'anesthésique générale. Pendant « un état hypnotique adéquat de l'anesthésie générale ¼, on remarquera fréquemment une phase-amplitude de fuseaux alpha (alpha-spindles phase amplitude) (d'environ 10 Hz) couplée à des ondes lentes delta (d'environ 1 Hz). De tels tracés peuvent être observés à partir de l'EEG ou sur un spectrogramme (un affichage par code couleur de la façon dont la puissance dans les diverses fréquences d'EEG se modifie au fil du temps). Toutefois, il existe des exceptions. Par exemple, l'administration de kétamine et de protoxyde d'azote n'est généralement pas associée au tracé de fréquence alpha couplé à l'onde delta susmentionné. En outre, certains patients, notamment des personnes plus âgées et les personnes souffrant de maladies neurodégénératives, sont moins prédisposés à générer un fort tracé électroencéphalographique de 'fréquence alpha' pendant une anesthésie générale. Dans de rares cas, le tracé de l'EEG frontal pourrait évoquer une anesthésie générale alors que le patient est encore quelque peu conscient et capable de suivre des ordres simples, mais ces situations surviennent habituellement sans détresse ni rétention de mémoire évidente. Par conséquent, l'EEG frontal seul tel qu'il est analysé à l'heure actuelle est un miroir clinique utile mais imparfait, et des recherches scientifiques seront nécessaires avant de pouvoir affirmer que nous disposons d'une mesure fiable de la « fonction ¼ cérébrale pendant l'anesthésie générale.

A narrative review of electroencephalogram-based monitoring during cardiovascular surgery.

PURPOSE OF REVIEW: The current narrative review focuses on depth of hypnosis monitoring with electroencephalography (EEG) during cardiovascular surgery. There have been important findings in recent years regarding the challenges and limitations of EEG-based monitoring during general anesthesia. The purpose of this review is to summarize key EEG-related concepts, as well as to highlight some of the advantages and disadvantages of processed and unprocessed EEG monitoring, especially for older patients with comorbidities undergoing cardiovascular surgery. RECENT FINDINGS: The brain is the target organ of anesthesia. Using the EEG or processed EEG to guide anesthetic administration during cardiovascular surgery conceptually allows precision patient-centered anesthesia. It is suggested that inadequate anesthesia, with the possibility of traumatic intraoperative awareness, can potentially be avoided. Furthermore, excessive anesthesia, with hemodynamic compromise and theoretical risk of delirium, can be minimized. Frail, older patients undergoing major surgery with preexisting neurocognitive disorders might be especially vulnerable to perioperative neurological and other complications. Tailoring anesthetic administration, based on individual patient needs partly guided by certain EEG features, might yield improved perioperative outcomes. SUMMARY: Ability to interpret the EEG during surgery might help anesthesia clinicians to individualize anesthetic administration to prevent adverse events, and optimize postoperative recovery.

Transient electroencephalographic alpha power loss during maintenance of general anaesthesia.

BACKGROUND: EEG activity in the extended alpha frequency range (7-17 Hz) during maintenance of general anaesthesia is primarily determined by effect-site concentrations of the hypnotic and analgesic drugs used. Intermittent alpha loss during surgery, unexplained by changes in anaesthetic or opioid concentrations, could represent arousal of the cortex as a result of increased surgical stimulation. METHODS: A generalised linear model was fitted to alpha power recorded from patients undergoing general anaesthesia from induction until waking using three explanatory variables: age-adjusted volatile anaesthetic effect-site concentration, and estimated effect-site propofol and opioid concentrations. Model residuals were decomposed into uncorrelated white noise and a fluctuating auto-correlated trend. Deviations of this local trend were classified as 'unexpected alpha dropout events'. To investigate whether these alpha dropouts might be explained by the effect of noxious stimulation, we related their occurrence to whether a patient was undergoing surgery involving the body cavity or not. RESULTS: Alpha power dropouts occurred in 73 of the 237 patients included in the final analysis (31%, median amplitude of -3.5 dB, duration=103 s). They showed a bimodal or broadly skewed distribution, being more probable soon after initial incision (32%), dropping to around 10% at 1 h, and then again increasing to >30% in operations lasting >3 h. Multivariate analysis showed that alpha dropouts were significantly associated with body cavity surgery (P=0.003) and with longer operations (P<0.001). CONCLUSIONS: A loss of alpha power, unexplained by changes in anaesthetic or opioid concentrations, is suggestive of thalamocortical depolarisation induced by body cavity noxious stimuli, and could provide a measure of nociception during surgery.

Suppression of underlying neuronal fluctuations mediates EEG slowing during general anaesthesia.

The physiological mechanisms by which anaesthetic drugs modulate oscillatory brain activity remain poorly understood. Combining human data, mathematical and computational analysis of both spiking and mean-field models, we investigated the spectral dynamics of encephalographic (EEG) beta-alpha oscillations, observed in human patients undergoing general anaesthesia. The effect of anaesthetics can be modelled as a reduction of neural fluctuation intensity, and/or an increase in inhibitory synaptic gain in the thalamo-cortical circuit. Unlike previous work, which suggested the primary importance of gamma-amino-butryic-acid (GABA) augmentation in causing a shift to low EEG frequencies, our analysis demonstrates that a non-linear transition, triggered by a simple decrease in neural fluctuation intensity, is sufficient to explain the clinically-observed appearance - and subsequent slowing - of the beta-alpha narrowband EEG peak. In our model, increased synaptic inhibition alone, did not correlate with the clinically-observed encephalographic spectral changes, but did cause the anaesthetic-induced decrease in neuronal firing rate. Taken together, our results show that such a non-linear transition results in functional fragmentation of cortical and thalamic populations; highly correlated intra-population dynamics triggered by anaesthesia decouple and isolate neural populations. Our results are able to parsimoniously unify and replicate the observed anaesthetic effects on both the EEG spectra and inter-regional connectivity, and further highlight the importance of neural activity fluctuations in the genesis of altered brain states.

Investigation of Slow-wave Activity Saturation during Surgical Anesthesia Reveals a Signature of Neural Inertia in Humans.

BACKGROUND: Previously, we showed experimentally that saturation of slow-wave activity provides a potentially individualized neurophysiologic endpoint for perception loss during anesthesia. Furthermore, it is clear that induction and emergence from anesthesia are not symmetrically reversible processes. The observed hysteresis is potentially underpinned by a neural inertia mechanism as proposed in animal studies. METHODS: In an advanced secondary analysis of 393 individual electroencephalographic data sets, we used slow-wave activity dose-response relationships to parameterize slow-wave activity saturation during induction and emergence from surgical anesthesia. We determined whether neural inertia exists in humans by comparing slow-wave activity dose responses on induction and emergence. RESULTS: Slow-wave activity saturation occurs for different anesthetics and when opioids and muscle relaxants are used during surgery. There was wide interpatient variability in the hypnotic concentrations required to achieve slow-wave activity saturation. Age negatively correlated with power at slow-wave activity saturation. On emergence, we observed abrupt decreases in slow-wave activity dose responses coincident with recovery of behavioral responsiveness in ~33% individuals. These patients are more likely to have lower power at slow-wave activity saturation, be older, and suffer from short-term confusion on emergence. CONCLUSIONS: Slow-wave activity saturation during surgical anesthesia implies that large variability in dosing is required to achieve a targeted potential loss of perception in individual patients. A signature for neural inertia in humans is the maintenance of slow-wave activity even in the presence of very-low hypnotic concentrations during emergence from anesthesia.

Electromyographic activation reveals cortical and sub-cortical dissociation during emergence from general anesthesia.

During emergence from anesthesia patients regain their muscle tone (EMG). In a typical population of surgical patients the actual volatile gas anesthetic concentrations in the brain (CeMAC) at which EMG activation occurs remains unknown, as is whether EMG activation at higher CeMACs is correlated with subsequent severe pain, or with cortical activation. Electroencephalographic (EEG) and EMG activity was recorded from the forehead of 273 patients emerging from general anesthesia following surgery. We determined CeMAC at time of EMG activation and at return of consciousness. Pain was assessed immediately after return of consciousness using an 11 point numerical rating scale. The onset of EMG activation during emergence was associated with neither discernible muscle movement nor with the presence of exogenous stimulation in half the patients. EMG activation could be modelled as two distinct processes; termed high- and low-CeMAC (occurring higher or lower than 0.07 CeMAC). Low-CeMAC activation was typically associated with simultaneous EMG activation and consciousness, and the presence of a laryngeal mask. In contrast, high-CeMAC EMG activation occurred independently of return of consciousness, and was not associated with severe post-operative pain, but was more common in the presence of an endotracheal tube. Patients emerging from general anesthesia with an endotracheal tube in place are more likely to have an EMG activation at higher CeMAC concentrations. These activations are not associated with subsequent high-pain, nor with cortical arousal, as evidenced by continuing delta waves in the EEG. Conversely, patients emerging from general anesthesia with a laryngeal mask demonstrate marked neural inertia-EMG activation occurs at a low CeMAC, and is closely temporally associated with return of consciousness.