Publications by authors named "Darren Hight"

25 Publications

  • Page 1 of 1

The influence of age on EEG-based anaesthesia indices.

J Clin Anesth 2021 Oct 8;73:110325. Epub 2021 May 8.

Department of Anesthesiology and Intensive Care Medicine, Technical University of Munich, School of Medicine, Munich, Germany. Electronic address:

Study Objective: In the upcoming years there will be a growing number of elderly patients requiring general anaesthesia. As age is an independent risk factor for postoperative delirium (POD) the incidence of POD will increase concordantly. One approach to reduce the risk of POD would be to avoid excessively high doses of anaesthetics by using neuromonitoring to guide anaesthesia titration. Therefore, we evaluated the influence of patient's age on various electroencephalogram (EEG)-based anaesthesia indices.

Design And Patients: We conducted an analysis of previously published data by replaying single electrode EEG episodes of maintenance of general anaesthesia from 180 patients (18-90 years; ASA I-IV) into the five different commercially available monitoring systems and evaluated their indices. We included the State/Response Entropy, Narcotrend, qCON/qNOX, bispectral index (BIS), and Treaton MGA-06. For a non-commercial comparison, we extracted the spectral edge frequency (SEF) from the BIS. To evaluate the influence of the age we generated linear regression models. We also assessed the correlation between the various indices.

Main Results: During anaesthetic maintenance the values of the SEF, State/Response Entropy, qCON/qNOX and BIS all significantly increased (0.05 Hz/0.19-0.26 index points per year) with the patient's age (p < 0.001); whereas the Narcotrend did not change significantly with age (0.06 index points per year; p = 0.28). The index values of the Treaton device significantly decreased with age (-0.09 index points per year; p < 0.001). These findings were independent of the administered dose of anaesthetics.

Conclusions: Almost all current neuromonitoring devices are influenced by age, with the potential to result in inappropriately high dosage of anaesthetics. Therefore, anaesthesiologists should be aware of this phenomenon, and the next generation of monitors should correct for these changes.
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http://dx.doi.org/10.1016/j.jclinane.2021.110325DOI Listing
October 2021

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

Br J Anaesth 2021 02;126(2):445-457

Department of Anaesthesiology, Waikato Clinical School, University of Auckland, Hamilton, New Zealand.

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.
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http://dx.doi.org/10.1016/j.bja.2020.10.036DOI Listing
February 2021

Correction to: An updated introduction to electroencephalogram-based brain monitoring duringintended general anesthesia.

Can J Anaesth 2021 Jan 11. Epub 2021 Jan 11.

Department of Anesthesiology, Washington University School of Medicine, 660 South Euclid Avenue, Campus Box 8054, St. Louis, MO, USA.

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http://dx.doi.org/10.1007/s12630-020-01877-0DOI Listing
January 2021

Correction to: An updated introduction to electroencephalogram-based brain monitoring during intended general anesthesia.

Can J Anaesth 2021 Jan 7. Epub 2021 Jan 7.

Department of Anesthesiology, Washington University School of Medicine, 660 South Euclid Avenue, Campus, Box 8054, St. Louis, MO, USA.

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http://dx.doi.org/10.1007/s12630-020-01891-2DOI Listing
January 2021

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

Can J Anaesth 2020 Dec 15;67(12):1858-1878. Epub 2020 Nov 15.

Department of Anesthesiology, Washington University School of Medicine, 660 South Euclid Avenue, Campus Box 8054, St. Louis, MO, USA.

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.
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http://dx.doi.org/10.1007/s12630-020-01820-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7666718PMC
December 2020

Entrainment of brain network oscillations in anaesthesia. Comment on Br J Anaesth 2020; 125: 330-335.

Br J Anaesth 2021 01 8;126(1):e11-e12. Epub 2020 Sep 8.

Department of Psychiatry, Carolina Center for Neurostimulation, University of North Carolina, Chapel Hill, NC, USA.

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http://dx.doi.org/10.1016/j.bja.2020.08.028DOI Listing
January 2021

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

Br J Anaesth 2020 10 31;125(4):456-465. Epub 2020 Jul 31.

Department of Anaesthesiology and Pain Medicine, Inselspital, Bern University Hospital, University of Bern, Switzerland.

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 (R=0.19) and broadband power (R=0.31). The association with peak alpha power is markedly reduced when the underlying broadband effect is subtracted (R=0.09). Broadband measures themselves are more strongly correlated with comorbidities and MAC (R=0.31) than age (R=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.
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http://dx.doi.org/10.1016/j.bja.2020.06.054DOI Listing
October 2020

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

Br J Anaesth 2020 09 15;125(3):291-297. Epub 2020 Jul 15.

Department of Anaesthesiology and Pain Medicine, Inselspital, Bern University Hospital, University of Bern, Switzerland.

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.
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http://dx.doi.org/10.1016/j.bja.2020.05.064DOI Listing
September 2020

Actimetry-Documented Persistent Periodic Limb Movements During EEG-Confirmed Deep General Anesthesia: A Case Report.

A A Pract 2020 Apr;14(6):e01183

Sleep-Wake-Epilepsy-Center, Department of Neurology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland.

Motor activity during general anesthesia (GA) without neuromuscular blockade is often interpreted as reflecting insufficient anesthesia. Here we present the case of an octogenarian undergoing deep sclerectomy with opioid-sparing electroencephalography (EEG)-guided anesthesia. Periodic leg movements (PLM) appeared during ongoing surgery while the patient's raw EEG displayed a pattern of deep anesthesia, evidenced by burst suppression. Recognizing PLM in the context of opioid-sparing GA is of importance for anesthesiologists, as deep anesthesia is not necessarily associated with a decrease in motor activity.
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http://dx.doi.org/10.1213/XAA.0000000000001183DOI Listing
April 2020

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

Anesthesiology 2020 05;132(5):1003-1016

From the Department of Anaesthesiology and Intensive Care, Klinikum rechts der Isar, Technical University Munich, Munich, Germany (M.K., S.B., G.S.) the Department of Anesthesiology (M.K., M.A.S., P.S.G.) the Medical Scientist Training Program (M.A.S.), Emory University School of Medicine, Atlanta, Georgia the Anesthesiology and Research Divisions, Atlanta Veterans Affairs Medical Center, (M.K., M.A.S., P.S.G.) Atlanta, Georgia the Department of Anaesthesia, Waikato Clinical School, University of Auckland, Hamilton, New Zealand (D.H., J.W.S.) the Waikato District Health Board, Hamilton, New Zealand (D.H., J.W.S.) the Department of Anaesthesiology and Pain Medicine, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland (D.H.) the Department of Anesthesiology, Columbia University Irving Medical Center, New York, New York (P.S.G.).

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.
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http://dx.doi.org/10.1097/ALN.0000000000003182DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7159998PMC
May 2020

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

Curr Opin Anaesthesiol 2020 Feb;33(1):92-100

Department of Anesthesiology, Washington University in St. Louis, St. Louis, Missouri, USA.

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.
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http://dx.doi.org/10.1097/ACO.0000000000000819DOI Listing
February 2020

A case report of several intraoperative convulsions while using the Narcotrend monitor: Significance and predictive use.

Medicine (Baltimore) 2019 Nov;98(47):e18004

Department of Anaesthesiology and Pain Medicine.

Introduction: Intraoperative seizures under general anesthesia are rare and our observation is the first to demonstrate a distinct electroencephalogram (EEG) pattern on the Narcotrend monitor.

Patient Concerns: We present the case of a 30-year-old man undergoing craniotomy for glioblastoma resection under general anesthesia who suffered tonic-clonic seizures captured in a specific pattern by the intraoperative EEG.

Diagnoses: Our depth of anesthesia monitor recorded, before the seizure, a widening of the beta-wave performance in a distinct "triangular-shaped" pattern. This pattern was repeated before the second seizure. The patient had no previous history of seizures and following surgery no further seizures were recorded.

Interventions: A spectrogram analysis showed a distinct increase in mean absolute beta power immediately prior to the first seizure. The EEG immediately prior to the second seizure was characterized by broadband noise. Both seizures were characterized by increased mean absolute delta, theta, and beta power.

Outcomes: The increase in EEG beta activity seen before the tonic-clonic movements may represent cortical irritability secondary to surgical manipulation, induced by electrical stimulation, reflecting progressive brain over-arousal. The attentive analysis of the relative beta power may have helped forecast the occurrence of the second seizure.

Lessons: We report the use of a simple, inexpensive, and portable EEG-based monitoring device to assist seizure detection and decision making.
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http://dx.doi.org/10.1097/MD.0000000000018004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6882640PMC
November 2019

Decreasing Frontal Electroencephalogram Alpha Power and Increasing Sensitivity to Volatile Anesthetics Over 3 Surgeries Within 7 Months: A Case Report.

A A Pract 2019 Oct;13(7):274-277

From the Department of Anaesthesiology and Pain Medicine, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland.

Depth of anesthesia (DoA) monitors are widely used during general anesthesia to guide individualized dosing of hypnotics. Other than age and specific drugs, there are few reports on which comorbidities may influence the brain and the resultant electroencephalogram (EEG) of patients undergoing general anesthesia. We present a case of a patient undergoing 3 cardiac operations within 7 months with severe illness and comorbidity, leading to pronounced physical frailty and significant changes of frontal alpha power in the EEG and increased sensitivity to volatile anesthetics. These findings may have important clinical implications and should trigger further investigations on this topic.
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http://dx.doi.org/10.1213/XAA.0000000000001053DOI Listing
October 2019

Transient electroencephalographic alpha power loss during maintenance of general anaesthesia.

Br J Anaesth 2019 May 30;122(5):635-642. Epub 2019 Jan 30.

Department of Anaesthesia, Waikato Clinical School, University of Auckland, Hamilton, New Zealand; Waikato District Health Board, Hamilton, New Zealand. Electronic address:

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.
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http://dx.doi.org/10.1016/j.bja.2018.11.029DOI Listing
May 2019

Modulation of frontal EEG alpha oscillations during maintenance and emergence phases of general anaesthesia to improve early neurocognitive recovery in older patients: protocol for a randomised controlled trial.

Trials 2019 Feb 22;20(1):146. Epub 2019 Feb 22.

Department of Anaesthesiology, Waikato Clinical Campus, University of Auckland, Hamilton, New Zealand.

Background: Postoperative delirium may manifest in the immediate post-anaesthesia care period. Such episodes appear to be predictive of further episodes of inpatient delirium and associated adverse outcomes. Frontal electroencephalogram (EEG) findings of suppression patterns and low proprietary index values have been associated with postoperative delirium and poor outcomes. However, the efficacy of titrating anaesthesia to proprietary index targets for preventing delirium remains contentious. We aim to assess the efficacy of two strategies which we hypothesise could prevent post-anaesthesia care unit (PACU) delirium by maximising the alpha oscillation observed in frontal EEG channels during the maintenance and emergence phases of anaesthesia.

Methods: This is a 2 × 2 factorial, double-blind, stratified, randomised control trial of 600 patients. Eligible patients are those aged 60 years or over who are undergoing non-cardiac, non-intracranial, volatile-based anaesthesia of expected duration of more than 2 h. Patients will be stratified by pre-operative cognitive status, surgery type and site. For the maintenance phase of anaesthesia, patients will be randomised (1:1) to an alpha power-maximisation anaesthesia titration strategy versus standard care avoiding suppression patterns in the EEG. For the emergence phase of anaesthesia, patients will be randomised (1:1) to early cessation of volatile anaesthesia and emergence from an intravenous infusion of propofol versus standard emergence from volatile anaesthesia only. The primary study outcomes are the power of the frontal alpha oscillation during the maintenance and emergence phases of anaesthesia. Our main clinical outcome of interest is PACU delirium.

Discussion: This is a largely exploratory study; the extent to which EEG signatures can be modified by titration of pharmacological agents is not known. The underlying concept is maximisation of anaesthetic efficacy by individualised drug titration to a clearly defined EEG feature. The interventions are already clinically used strategies in anaesthetic practice, but have not been formally evaluated. The addition of propofol during the emergence phase of volatile-based general anaesthesia is known to reduce emergence delirium in children; however, the efficacy of this strategy in older patients is not known.

Trial Registration: Australian and New Zealand Clinical Trial Registry, ID: 12617001354370 . Registered on 27/09/2017.
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http://dx.doi.org/10.1186/s13063-019-3178-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6387545PMC
February 2019

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

Neuroimage 2018 10 18;179:414-428. Epub 2018 Jun 18.

Department of Anaesthesiology, Waikato Clinical Campus, University of Auckland, Hamilton, 3240, New Zealand. Electronic address:

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.
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http://dx.doi.org/10.1016/j.neuroimage.2018.06.043DOI Listing
October 2018

Inattentive Delirium vs. Disorganized Thinking: A New Axis to Subcategorize PACU Delirium.

Front Syst Neurosci 2018 23;12:22. Epub 2018 May 23.

Research Division, Atlanta VA Medical Center, Atlanta, GA, United States.

Assessment of patients for delirium in the Post Anesthesia Care Unit (PACU) is confounded by the residual effects of the varied anesthetic and analgesic regimens employed during surgery and by the physiological consequences of surgery such as pain. Nevertheless, delirium diagnosed at this early stage has been associated with adverse clinical outcomes. The last decade has seen the emergence of the confusion assessment method-intensive care unit (CAM-ICU) score as a quick practical method of detecting delirium in clinical situations. Nonetheless, this tool has not been specifically designed for use in this immediate postoperative setting. Patients enrolled in a larger observational study were administered the CAM-ICU delirium screening tool 15 min after the latter of return of responsiveness to command or arrival in the post-anesthesia care unit. Numerical pain rating scores were also recorded. In addition, we reviewed additional behavioral observations suggestive of disordered thinking, such as hallucinations, a non-reactive eyes-open state, or an inability to state a pain score. Two-hundred and twenty-nine patients underwent CAM-ICU testing in PACU. 33 patients (14%) were diagnosed with delirium according to CAM-ICU criteria; 25 of these were inattentive with low arousal, seven were inattentive with high arousal, and one was inattentive and calm and with disordered thinking. Using our extended criteria an additional eleven patients showed signs of disordered thinking. CAM-ICU delirium was associated with increased length of operation ( = 0.028), but a positive CAM-PACU designation was associated with both increased operation length and age ( = 0.003 and 0.010 respectively). Two of the CAM-ICU positive patients with inattention and high arousal reported high pain scores and were not classified as CAM-PACU positive. Disordered thinking is correlated with older patients and longer operations. The sensitivity of the existing CAM-ICU score in diagnosing delirium or disordered thinking in PACU patients is improved by the inclusion of a few extra criteria, namely: patients having perceptual hallucinations, in an unreactive eyes-open state, or who cannot state a pain score. We present this alternative screening tool for use in the post-anesthetic period, which we have named CAM-PACU.
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http://dx.doi.org/10.3389/fnsys.2018.00022DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5974154PMC
May 2018

Emergence EEG pattern classification in sevoflurane anesthesia.

Physiol Meas 2018 04 26;39(4):045006. Epub 2018 Apr 26.

Institute of Electrical Engineering, Yanshan University, Qinhuangdao, People's Republic of China.

Objective: Significant spectral electroencephalogram (EEG) pattern characteristics exist in individual patients during the re-establishment of consciousness after general anesthesia. However, these EEG patterns cannot be quantitatively identified using commercially available depth of anesthesia (DoA) monitors. This study proposes an effective classification method and indices to classify these patterns among patients.

Approach: Four types of emergence EEG patterns were identified based on the EEG data set from 52 patients undergoing sevoflurane general anesthesia from two hospitals. Then, the relative power spectrum density (RPSD) of five frequency sub-bands of clinical interest (delta, theta, alpha, beta and gamma) were selected for emergence state analysis. Finally, a genetic algorithm support vector machine (GA-SVM) was used to identify the emergence EEG patterns. The performance was reported in terms of sensitivity (SE), specificity (SP) and accuracy (AC).

Main Results: The combination of the mean and mode of RPSD in the delta and alpha band (P (delta)/P (alpha) performed the best in the GA-SVM classification. The AC indices obtained by GA-SVM across the four patterns were 90.64  ±  7.61, 81.79  ±  5.84, 82.14  ±  7.99 and 72.86  ±  11.11 respectively. Furthermore, the emergence time of the patients with EEG emergence patterns I and III increased as the patients' age increased. However, for patients with EEG emergence pattern IV, the emergence time positively correlates with the patients' age when they are under 50, and negatively correlates with it when they are over 50.

Significance: The mean and mode of P (delta)/P (alpha) is a useful index to classify the different emergence EEG patterns. In addition, these patterns may correlate with an underlying neural substrate which is related to the patients' age. Highlights ► Four emergence EEG patterns were found in γ-amino-butyric acid (GABA)-ergic anesthetic drugs. ► A genetic algorithm combined with a support vector machine (GA-SVM) was proposed to identify the emergence EEG patterns. ► The relative power spectrum density (RPSD) was used as a feature to classify the emergence EEG patterns and good accuracy was achieved. ► The statistics shows that the emergence EEG patterns are age-related and may have value in assessing postoperative brain states.
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http://dx.doi.org/10.1088/1361-6579/aab4d0DOI Listing
April 2018

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

Anesthesiology 2017 10;127(4):645-657

From the Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, United Kingdom (C.E.W., S.J., I.T.); and Department of Anaesthesia, University of Auckland, Waikato Hospital, Hamilton, New Zealand (J.W.S., D.H.).

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.
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http://dx.doi.org/10.1097/ALN.0000000000001759DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7116592PMC
October 2017

Anesthetic action on the transmission delay between cortex and thalamus explains the beta-buzz observed under propofol anesthesia.

PLoS One 2017 16;12(6):e0179286. Epub 2017 Jun 16.

University of Auckland, Hamilton, New Zealand.

In recent years, more and more surgeries under general anesthesia have been performed with the assistance of electroencephalogram (EEG) monitors. An increase in anesthetic concentration leads to characteristic changes in the power spectra of the EEG. Although tracking the anesthetic-induced changes in EEG rhythms can be employed to estimate the depth of anesthesia, their precise underlying mechanisms are still unknown. A prominent feature in the EEG of some patients is the emergence of a strong power peak in the β-frequency band, which moves to the α-frequency band while increasing the anesthetic concentration. This feature is called the beta-buzz. In the present study, we use a thalamo-cortical neural population feedback model to reproduce observed characteristic features in frontal EEG power obtained experimentally during propofol general anesthesia, such as this beta-buzz. First, we find that the spectral power peak in the α- and δ-frequency ranges depend on the decay rate constant of excitatory and inhibitory synapses, but the anesthetic action on synapses does not explain the beta-buzz. Moreover, considering the action of propofol on the transmission delay between cortex and thalamus, the model reveals that the beta-buzz may result from a prolongation of the transmission delay by increasing propofol concentration. A corresponding relationship between transmission delay and anesthetic blood concentration is derived. Finally, an analytical stability study demonstrates that increasing propofol concentration moves the systems resting state towards its stability threshold.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0179286PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5473556PMC
September 2017

Changes in Alpha Frequency and Power of the Electroencephalogram during Volatile-Based General Anesthesia.

Front Syst Neurosci 2017 29;11:36. Epub 2017 May 29.

Department of Anaesthesia, Waikato Clinical Campus, University of AucklandHamilton, New Zealand.

Oscillations in the electroencephalogram (EEG) at the alpha frequency (8-12 Hz) are thought to be ubiquitous during surgical anesthesia, but the details of how this oscillation responds to ongoing changes in volatile anesthetic concentration have not been well characterized. It is not known how often alpha oscillations are absent in the clinical context, how sensitively alpha frequency and power respond to changes in anesthetic concentration, and what effect increased age has on alpha frequency. Bipolar EEG was recorded frontally from 305 patients undergoing surgery with sevoflurane or desflurane providing general anesthesia. A new method of detecting the presence of alpha oscillations based on the stability of the rate of change of the peak frequency in the alpha range was developed. Linear concentration-response curves were fitted to assess the sensitivity of alpha power and frequency measures to changing levels of anesthesia. Alpha oscillations were seen to be inexplicably absent in around 4% of patients. Maximal alpha power increased with increasing volatile anesthetic concentrations in half of the patients, and decreased in the remaining patients. Alpha frequency decreased with increasing anesthetic concentrations in near to 90% of patients. Increasing age was associated with decreased sensitivity to volatile anesthesia concentrations, and with decreased alpha frequency, which sometimes transitioned into the theta range (5-7 Hz). While peak alpha frequency shows a consistent slowing to increasing volatile concentrations, the peak power of the oscillation does not, suggesting that frequency might be more informative of depth of anesthesia than traditional power based measures during volatile-based anesthesia. The alpha oscillation becomes slower with increasing age, even when the decreased anesthetic needs of older patients were taken into account.
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http://dx.doi.org/10.3389/fnsys.2017.00036DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5446988PMC
May 2017

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

J Clin Monit Comput 2017 Aug 21;31(4):813-823. Epub 2016 Jul 21.

Department of Anaesthesiology, Waikato Clinical Campus, University of Auckland, Pembroke Street, Hamilton, 3240, New Zealand.

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 (CMAC) at which EMG activation occurs remains unknown, as is whether EMG activation at higher CMACs 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 CMAC 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-CMAC (occurring higher or lower than 0.07 CMAC). Low-CMAC activation was typically associated with simultaneous EMG activation and consciousness, and the presence of a laryngeal mask. In contrast, high-CMAC 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 CMAC 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 CMAC, and is closely temporally associated with return of consciousness.
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http://dx.doi.org/10.1007/s10877-016-9911-zDOI Listing
August 2017

What would a proper explanation of anesthesia look like?

Anesthesiology 2015 Jun;122(6):1196-7

From the Department of Anaesthesia, Waikato Clinical School, University of Auckland, Hamilton, New Zealand.

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http://dx.doi.org/10.1097/ALN.0000000000000672DOI Listing
June 2015

Emergence from general anesthesia and the sleep-manifold.

Front Syst Neurosci 2014 13;8:146. Epub 2014 Aug 13.

Department of Anaesthesiology, Waikato Clinical School, University of Auckland Hamilton, New Zealand.

The electroencephalogram (EEG) during the re-establishment of consciousness after general anesthesia and surgery varies starkly between patients. Can the EEG during this emergence period provide a means of estimating the underlying biological processes underpinning the return of consciousness? Can we use a model to infer these biological processes from the EEG patterns? A frontal EEG was recorded from 84 patients. Ten patients were chosen for state-space analysis. Five showed archetypal emergences; which consisted of a progressive decrease in alpha power and increase peak alpha frequency before return of responsiveness. The five non-archetypal emergences showed almost no spectral EEG changes (even as the volatile general anesthetic decreased) and then an abrupt return of responsiveness. We used Bayesian methods to estimate the likelihood of an EEG pattern corresponding to the position of the patient on a 2-dimensional manifold in a state space of excitatory connection strength vs. change in intrinsic resting neuronal membrane conductivity. We could thus visualize the trajectory of each patient in the state-space during their emergence period. The patients who followed an archetypal emergence displayed a very consistent pattern; consisting of progressive increase in conductivity, and a temporary period of increased connection strength before return of responsiveness. The non-archetypal emergence trajectories remained fixed in a region of phase space characterized by a relatively high conductivity and low connection strength throughout emergence. This unexpected progressive increase in conductivity during archetypal emergence may be due to an abating of the surgical stimulus during this period. Periods of high connection strength could represent forays into dissociated consciousness, but the model suggests all patients reposition near the fold in the state space to take advantage of bi-stable cortical dynamics before transitioning to consciousness.
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http://dx.doi.org/10.3389/fnsys.2014.00146DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4131673PMC
August 2014

Improved characterization of visual evoked potentials in multiple sclerosis by topographic analysis.

Brain Topogr 2014 Mar 2;27(2):318-27. Epub 2013 Oct 2.

Department of Neurology, Hospital of the University of Basel, Petersgraben 4, 4031, Basel, Switzerland,

In multiple sclerosis (MS), the combination of visual, somatosensory and motor evoked potentials (EP) has been shown to be highly correlated with the Expanded Disability Severity Scale (EDSS) and to predict the disease course. In the present study, we explored whether the significance of the visual EP (VEP) can be improved with multichannel recordings (204 electrodes) and topographic analysis (tVEP). VEPs were analyzed in 83 MS patients (median EDSS 2.0; 52 % with history of optic neuritis; hON) and 47 healthy controls (HC). TVEP components were automatically defined on the basis of spatial similarity between the scalp potential fields (topographic maps) of single subjects' VEPs and reference maps generated from HC. Non-ambiguous measures of latency, amplitude and configuration were derived from the maps reflecting the P100 component. TVEP was compared to conventional analysis (cVEP) with respect to reliability in HC, validity using descriptors of logistic regression models, and sensitivity derived from receiver operating characteristics curves. In tVEP, reliability tended to be higher for measurement of amplitude (p = 0.06). Regression models on diagnosis (MS vs. HC) and hON were more favorable using tVEP- versus cVEP-predictors. Sensitivity was increased in tVEP versus cVEP: 72 % versus 60 % for diagnosis, and 88 % versus 77 % for hON. The advantage of tVEP was most pronounced in pathological VEPs, in which cVEPs were often ambiguous. TVEP is a reliable, valid, and sensitive method of objectively quantifying pathological VEP in particular. In combination with other EP modalities, tVEP may improve the monitoring of disease course in MS.
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http://dx.doi.org/10.1007/s10548-013-0318-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3921459PMC
March 2014