Publications by authors named "Paul S García"

67 Publications

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

Anesthetic Management for Endovascular Treatment of Stroke in Patients With Coronavirus Disease 2019: A Case Series.

A A Pract 2021 May 7;15(5):e01458. Epub 2021 May 7.

From the Department of Anesthesiology, Columbia University Medical Center, NewYork-Presbyterian Hospital, New York, New York.

A significant number of patients with coronavirus disease 2019 develop strokes with large vessel obstructions that may require endovascular treatment for revascularization. Our series focuses on periprocedural issues and the anesthetic management of these patients. We analyzed medical records of 5 patients with positive reverse transcription polymerase chain reaction tests for severe acute respiratory syndrome coronavirus 2 during their hospitalization who underwent endovascular treatment at our hospital between March and mid-June 2020. We found that our patients were different from the typical patients with ischemic stroke in that they had signs of hypercoagulability, hypoxia, and a lack of hypertension at presentation.
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http://dx.doi.org/10.1213/XAA.0000000000001458DOI Listing
May 2021

Prehabilitative exercise hastens recovery from isoflurane in diabetic and non-diabetic rats.

Neurosci Lett 2021 04 8;751:135808. Epub 2021 Mar 8.

Neuroscience Program, Emory University, Atlanta, GA, USA; School of Medicine, Emory University, Atlanta, GA, USA; Center for Visual and Neurocognitive Rehabilitation, Atlanta VA Health Care System, Decatur, GA, USA; Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology, Atlanta, GA, USA; Department of Anesthesiology, Emory University School of Medicine, Atlanta, GA, USA; Department of Anesthesiology, Columbia University Medical Center, New York, NY, USA. Electronic address:

Diabetes has been demonstrated to be one of the strongest predictors of risk for postoperative delirium and functional decline in older patients undergoing surgery. Exercise is often prescribed as a treatment for diabetic patients and regular physical activity is hypothesized to decrease the risk of postoperative cognitive impairments. Prior studies suggest that anesthetic emergence trajectories and recovery are predictive of risk for later postoperative cognitive impairments. Therapeutic strategies aimed at improving emergence and recovery from anesthesia may therefore be beneficial for diabetic patients. Wistar (n = 32) and Goto-Kakizaki (GK) type 2 diabetic (n = 32) rats between 3-4 months old underwent treadmill exercise for 30 min/day for ten days or remained inactive. Pre-anesthesia spontaneous alternation behavior was recorded with a Y-maze. Rats then received a 2-h exposure to 1.5-2 % isoflurane or oxygen only. The time to reach anesthetic emergence and post-anesthesia recovery behaviors was recorded for each rat. Postsynaptic density protein-95 (PSD-95), an important scaffolding protein required for synaptic plasticity, protein levels were quantified from hippocampus using western blot. Spontaneous alternation behavior (p = 0.044) and arm entries (p < 0.001) were decreased in GK rats. There was no difference between groups in emergence times from isoflurane, but exercise hastened the recovery time (p = 0.008) for both Wistar and GK rats. Following 10 days of exercise, both Wistar and GK rats show increased levels of PSD-95 in the hippocampus. Prehabilitation with moderate intensity exercise, even on a short timescale, is beneficial for recovery from isoflurane in rats, regardless of metabolic disease status.
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http://dx.doi.org/10.1016/j.neulet.2021.135808DOI Listing
April 2021

Roadmap for Conducting Neuroscience Research in the COVID-19 Era and Beyond: Recommendations From the SNACC Research Committee.

J Neurosurg Anesthesiol 2021 Apr;33(2):100-106

Department of Anesthesiology and Perioperative Medicine, Oregon Health and Science University, Portland, OR.

The coronavirus disease 2019 (COVID-19) pandemic has impacted many aspects of neuroscience research. At the 2020 Society of Neuroscience in Anesthesiology and Critical Care (SNACC) Annual Meeting, the SNACC Research Committee met virtually to discuss research challenges encountered during the COVID-19 pandemic along with possible strategies for facilitating research activities. These challenges and recommendations are included in this Consensus Statement. The objectives are to: (1) provide an overview of the disruptions and challenges to neuroscience research caused by the COVID-19 pandemic, and; (2) put forth a set of consensus recommendations for strengthening research sustainability during and beyond the current pandemic. Specific recommendations are highlighted for adapting laboratory and human subject study activities to optimize safety. Complementary research activities are also outlined for both laboratory and clinical researchers if specific investigations are impossible because of regulatory or societal changes. The role of virtual platforms is discussed with respect to fostering new collaborations, scheduling research meetings, and holding conferences such that scientific collaboration and exchange of ideas can continue. Our hope is for these recommendations to serve as a valuable resource for investigators in the neurosciences and other research disciplines for current and future research disruptions.
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http://dx.doi.org/10.1097/ANA.0000000000000758DOI Listing
April 2021

Repetitive Anodal Transcranial Direct Current Stimulation Hastens Isoflurane-Induced Emergence and Recovery and Enhances Memory in Healthy Rats.

Anesth Analg 2021 05;132(5):1347-1358

From the Neuroanesthesia Laboratory, Atlanta VA Medical Center, Emory University, Atlanta, Georgia.

Background: Attaining a rapid and smooth return to consciousness after general anesthesia is a goal for clinical anesthesiologists. This study aimed to investigate the effects of repeated anodal transcranial direct current stimulation (atDCS) on emergence and recovery from isoflurane anesthesia in rats.

Methods: Four days after surgery for atDCS socket implantation, rats received either sham stimulation or repetitive anodal direct electrical current of 0.2 mA intensity applied to the right motor cortex for 20 minutes/d for 10 consecutive days. Isoflurane potency and emergence and recovery from a 2-hour isoflurane challenge were evaluated 24 hours after the last atDCS session. Cognitive performance on novel object recognition and spontaneous alternation Y-maze tests were measured 48 hours after the last atDCS session. Locomotor activity was assessed via automated counting of electric infrared beam crossings.

Results: Data are expressed as mean ± standard error of mean (SEM). Isoflurane potency was not affected by atDCS (sham: 1.69% ± 0.06%, transcranial direct current stimulation [tDCS]: 1.73% ± 0.11%, mean difference [MD]: 0.045, 95% confidence interval [CI]: -0.22 to 0.30; P = .72). However, the time to appearance of emergence behavioral marker (eg, return of righting reflex) was hastened in rats receiving atDCS (sham: 486 ± 31 seconds, tDCS: 330 ± 45 seconds, MD: 157, 95% CI: 30-284; P = .008). Similarly, time to acknowledgment of adhesive tape ("sticky dot" applied while anesthetized) was also decreased in atDCS-treated rats as compared to sham (sham: 1374 ± 179 seconds, tDCS: 908 ± 151 seconds, MD: 466, 95% CI: 73-858; P = .015), indicating a faster recovery of isoflurane anesthesia. Rats treated with atDCS spent more time exploring the novel object and environment when compared to sham without affecting activity cycles, indicating visual and working memory can be enhanced by atDCS.

Conclusions: Taken together, our findings suggest that atDCS over cortical areas might hasten recovery from isoflurane anesthesia and could potentially be used as a preventative strategy for disruptions in higher order functions related to sedation/anesthesia.
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http://dx.doi.org/10.1213/ANE.0000000000005379DOI Listing
May 2021

Frontotemporal EEG to guide sedation in COVID-19 related acute respiratory distress syndrome.

Clin Neurophysiol 2021 03 20;132(3):730-736. Epub 2021 Jan 20.

Department of Neurology, Columbia University Irving Medical Center, New York, NY, USA. Electronic address:

Objective: To study if limited frontotemporal electroencephalogram (EEG) can guide sedation changes in highly infectious novel coronavirus disease 2019 (COVID-19) patients receiving neuromuscular blocking agent.

Methods: 98 days of continuous frontotemporal EEG from 11 consecutive patients was evaluated daily by an epileptologist to recommend reduction or maintenance of the sedative level. We evaluated the need to increase sedation in the 6 h following this recommendation. Post-hoc analysis of the quantitative EEG was correlated with the level of sedation using a machine learning algorithm.

Results: Eleven patients were studied for a total of ninety-eight sedation days. EEG was consistent with excessive sedation on 57 (58%) and adequate sedation on 41 days (42%). Recommendations were followed by the team on 59% (N = 58; 19 to reduce and 39 to keep the sedation level). In the 6 h following reduction in sedation, increases of sedation were needed in 7 (12%). Automatized classification of EEG sedation levels reached 80% (±17%) accuracy.

Conclusions: Visual inspection of a limited EEG helped sedation depth guidance. In a secondary analysis, our data supported that this determination may be automated using quantitative EEG analysis.

Significance: Our results support the use of frontotemporal EEG for guiding sedation in patients with COVID-19.
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http://dx.doi.org/10.1016/j.clinph.2021.01.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7817418PMC
March 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

Age-Related EEG Features of Bursting Activity During Anesthetic-Induced Burst Suppression.

Front Syst Neurosci 2020 3;14:599962. Epub 2020 Dec 3.

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

Electroencephalographic (EEG) Burst Suppression (BSUPP) is a discontinuous pattern characterized by episodes of low voltage disrupted by bursts of cortical synaptic activity. It can occur while delivering high-dose anesthesia. Current research suggests an association between BSUPP and the occurrence of postoperative delirium in the post-anesthesia care unit (PACU) and beyond. We investigated burst micro-architecture to further understand how age influences the neurophysiology of this pharmacologically-induced state. We analyzed a subset of EEG recordings ( = 102) taken from a larger data set previously published. We selected the initial burst that followed a visually identified "silent second," i.e., at least 1 s of iso-electricity of the EEG during propofol induction. We derived the (normalized) power spectral density [(n)PSD], the alpha band power, the maximum amplitude, the maximum slope of the EEG as well as the permutation entropy (PeEn) for the first 1.5 s of the initial burst of each patient. In the old patients >65 years, we observed significantly lower ( < 0.001) EEG power in the 1-15 Hz range. In general, their EEG contained a significantly higher amount of faster oscillations (>15 Hz). Alpha band power ( < 0.001), EEG amplitude ( = 0.001), and maximum EEG slope ( = 0.045) all significantly decreased with age, whereas PeEn increased ( = 0.008). Hence, we can describe an age-related change in features during EEG burst suppression. Sub-group analysis revealed no change in results based on pre-medication. These EEG changes add knowledge to the impact of age on cortical synaptic activity. In addition to a reduction in EEG amplitude, age-associated burst features can complicate the identification of excessive anesthetic administration in patients under general anesthesia. Knowledge of these neurophysiologic changes may not only improve anesthesia care through improved detection of burst suppression but might also provide insight into changes in neuronal network organization in patients at risk for age-related neurocognitive problems.
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http://dx.doi.org/10.3389/fnsys.2020.599962DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7744408PMC
December 2020

Sleep/Wake Behavior and EEG Signatures of the TgF344-AD Rat Model at the Prodromal Stage.

Int J Mol Sci 2020 Dec 5;21(23). Epub 2020 Dec 5.

Department of Anesthesiology, Emory University, Atlanta, GA 30322, USA.

Transgenic modification of the two most common genes (APPsw, PS1ΔE9) related to familial Alzheimer's disease (AD) in rats has produced a rodent model that develops pathognomonic signs of AD without genetic tau-protein modification. We used 17-month-old AD rats ( = 8) and age-matched controls (AC, = 7) to evaluate differences in sleep behavior and EEG features during wakefulness (WAKE), non-rapid eye movement sleep (NREM), and rapid eye movement sleep (REM) over 24-h EEG recording (12:12h dark-light cycle). We discovered that AD rats had more sleep-wake transitions and an increased probability of shorter REM and NREM bouts. AD rats also expressed a more uniform distribution of the relative spectral power. Through analysis of information content in the EEG using entropy of difference, AD animals demonstrated less EEG information during WAKE, but more information during NREM. This seems to indicate a limited range of changes in EEG activity that could be caused by an AD-induced change in inhibitory network function as reflected by increased GABAAR-β2 expression but no increase in GAD-67 in AD animals. In conclusion, this transgenic rat model of Alzheimer's disease demonstrates less obvious EEG features of WAKE during wakefulness and less canonical features of sleep during sleep.
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http://dx.doi.org/10.3390/ijms21239290DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7730237PMC
December 2020

Meta-analysis and Megadata in Electroencephalogram-Based Techniques for Delirium Prevention.

Authors:
Paul S García

Anesth Analg 2020 09;131(3):709-711

From the Department of Anesthesiology, Columbia University Medical Center, New York, New York.

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http://dx.doi.org/10.1213/ANE.0000000000004867DOI Listing
September 2020

Propofol Affects Cortico-Hippocampal Interactions via β3 Subunit-Containing GABA Receptors.

Int J Mol Sci 2020 Aug 14;21(16). Epub 2020 Aug 14.

Department of Anaesthesiology, Experimental Anaesthesiology Section, Eberhard-Karls-University, Waldhörnlestrasse 22, 72072 Tübingen, Germany.

Background: General anesthetics depress neuronal activity. The depression and uncoupling of cortico-hippocampal activity may contribute to anesthetic-induced amnesia. However, the molecular targets involved in this process are not fully characterized. GABA receptors, especially the type with β3 subunits, represent a main molecular target of propofol. We therefore hypothesized that GABA receptors with β3 subunits mediate the propofol-induced disturbance of cortico-hippocampal interactions.

Methods: We used local field potential (LFP) recordings from chronically implanted cortical and hippocampal electrodes in wild-type and β3(N265M) knock-in mice. In the β3(N265M) mice, the action of propofol via β3subunit containing GABA receptors is strongly attenuated. The analytical approach contained spectral power, phase locking, and mutual information analyses in the 2-16 Hz range to investigate propofol-induced effects on cortico-hippocampal interactions.

Results: Propofol caused a significant increase in spectral power between 14 and 16 Hz in the cortex and hippocampus of wild-type mice. This increase was absent in the β3(N265M) mutant. Propofol strongly decreased phase locking of 6-12 Hz oscillations in wild-type mice. This decrease was attenuated in the β3(N265M) mutant. Finally, propofol reduced the mutual information between 6-16 Hz in wild-type mice, but only between 6 and 8 Hz in the β3(N265M) mutant.

Conclusions: GABA receptors containing β3 subunits contribute to frequency-specific perturbation of cortico-hippocampal interactions. This likely explains some of the amnestic actions of propofol.
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http://dx.doi.org/10.3390/ijms21165844DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7461501PMC
August 2020

Technical considerations when using the EEG export of the SEDLine Root device.

J Clin Monit Comput 2020 Aug 19. Epub 2020 Aug 19.

Department of Anesthesiology and Intensive Care, Klinikum rechts der Isar, School of Medicine, Technical University of Munich, Munich, Germany.

Electroencephalographic (EEG) patient monitoring during general anesthesia can help to assess the real-time neurophysiology of unconscious states. Some monitoring systems like the SEDLine Root allow export of the EEG to be used for retrospective analysis. We show that changes made to the SEDLine display during recording affected the recorded EEG. These changes can strongly impact retrospective analysis of EEG signals. Real-time changes of the feed speed in the SEDLine Root device display modifies the sampling rate of the exported EEG. We used a patient as well as a simulated EEG recording to highlight the effects of the display settings on the extracted EEG. Therefore, we changed EEG feed and amplitude resolution on the display in a systematic manner. To visualize the effects of these changes, we present raw EEG segments and the density spectral array of the recording. Changing the display's amplitude resolution affects the amplitudes. If the amplitude resolution is too fine, the exported EEG contains clipped amplitudes. If the resolution is too coarse, the EEG resolution becomes too low leading to a low-quality signal making frequency analysis impossible. The proportion of clipped or zero-line data caused by the amplitude setting was > 60% in our sedated patient. Changing the display settings results in undocumented changes in EEG amplitude, sampling rate, and signal quality. The occult nature of these changes could make the analysis of data sets difficult if not invalid. We strongly suggest researchers adequately define and keep the EEG display settings to export good quality EEG and to ensure comparability among patients.
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http://dx.doi.org/10.1007/s10877-020-00578-9DOI Listing
August 2020

Association of Delirium With Long-term Cognitive Decline: A Meta-analysis.

JAMA Neurol 2020 11;77(11):1373-1381

Department of Anesthesiology, Columbia University Irving Medical Center, New York, New York.

Importance: Delirium is associated with increased hospital costs, health care complications, and increased mortality. Long-term consequences of delirium on cognition have not been synthesized and quantified via meta-analysis.

Objective: To determine if an episode of delirium was an independent risk factor for long-term cognitive decline, and if it was, whether it was causative or an epiphenomenon in already compromised individuals.

Data Sources: A systematic search in PubMed, Cochrane, and Embase was conducted from January 1, 1965, to December 31, 2018. A systematic review guided by Preferred Reporting Items for Systematic Reviews and Meta-analyses was conducted. Search terms included delirium AND postoperative cognitive dysfunction; delirium and cognitive decline; delirium AND dementia; and delirium AND memory.

Study Selection: Inclusion criteria for studies included contrast between groups with delirium and without delirium; an objective continuous or binary measure of cognitive outcome; a final time point of 3 or more months after the delirium episode. The electronic search was conducted according to established methodologies and was executed on October 17, 2018.

Data Extraction And Synthesis: Three authors extracted data on individual characteristics, study design, and outcome, followed by a second independent check on outcome measures. Effect sizes were calculated as Hedges g. If necessary, binary outcomes were also converted to g. Only a single effect size was calculated for each study.

Main Outcomes And Measures: The planned main outcome was magnitude of cognitive decline in Hedges g effect size in delirium groups when contrasted with groups that did not experience delirium.

Results: Of 1583 articles, data subjected from the 24 studies (including 3562 patients who experienced delirium and 6987 controls who did not) were included in a random-effects meta-analysis for pooled effect estimates and random-effects meta-regressions to identify sources of study variance. One study was excluded as an outlier. There was a significant association between delirium and long-term cognitive decline, as the estimated effect size (Hedges g) for 23 studies was 0.45 (95% CI, 0.34-0.57; P < .001). In all studies, the group that experienced delirium had worse cognition at the final time point. The I2 measure of between-study variability in g was 0.81. A multivariable meta-regression suggested that duration of follow-up (longer with larger gs), number of covariates controlled (greater numbers were associated with smaller gs), and baseline cognitive matching (matching was associated with larger gs) were significant sources of variance. More specialized subgroup and meta-regressions were consistent with predictions that suggested that delirium may be a causative factor in cognitive decline.

Conclusions And Relevance: In this meta-analysis, delirium was significantly associated with long-term cognitive decline in both surgical and nonsurgical patients.
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http://dx.doi.org/10.1001/jamaneurol.2020.2273DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7358977PMC
November 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

Diazepam and ethanol differently modulate neuronal activity in organotypic cortical cultures.

BMC Neurosci 2019 12 10;20(1):58. Epub 2019 Dec 10.

Dept. of Anesthesiology and Intensive Care, Experimental Anesthesiology Section, University Hospital Tübingen, Tübingen, Germany.

Background: The pharmacodynamic results of diazepam and ethanol administration are similar, in that each can mediate amnestic and sedative-hypnotic effects. Although each of these molecules effectively reduce the activity of central neurons, diazepam does so through modulation of a more specific set of receptor targets (GABA receptors containing a γ-subunit), while alcohol is less selective in its receptor bioactivity. Our investigation focuses on divergent actions of diazepam and ethanol on the firing patterns of cultured cortical neurons.

Method: We used electrophysiological recordings from organotypic slice cultures derived from Sprague-Dawley rat neocortex. We exposed these cultures to either diazepam (15 and 30 µM, n = 7) or ethanol (30 and 60 mM, n = 11) and recorded the electrical activity at baseline and experimental conditions. For analysis, we extracted the episodes of spontaneous activity, i.e., cortical up-states. After separation of action potential and local field potential (LFP) activity, we looked at differences in the number of action potentials, in the spectral power of the LFP, as well as in the coupling between action potential and LFP phase.

Results: While both substances seem to decrease neocortical action potential firing in a not significantly different (p = 0.659, Mann-Whitney U) fashion, diazepam increases the spectral power of the up-state without significantly impacting the spectral composition, whereas ethanol does not significantly change the spectral power but the oscillatory architecture of the up-state as revealed by the Friedman test with Bonferroni correction (p < 0.05). Further, the action potential to LFP-phase coupling reveals a synchronizing effect of diazepam for a wide frequency range and a narrow-band de-synchronizing effect for ethanol (p < 0.05, Kolmogorov-Smirnov test).

Conclusion: Diazepam and ethanol, induce specific patterns of network depressant actions. Diazepam induces cortical network inhibition and increased synchronicity via gamma subunit containing GABA receptors. Ethanol also induces cortical network inhibition, but without an increase in synchronicity via a wider span of molecular targets.
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http://dx.doi.org/10.1186/s12868-019-0540-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6902402PMC
December 2019

American Society for Enhanced Recovery and Perioperative Quality Initiative Joint Consensus Statement on the Role of Neuromonitoring in Perioperative Outcomes: Electroencephalography.

Anesth Analg 2020 05;130(5):1278-1291

Department of Anesthesiology, Stony Brook School of Medicine, Stony Brook, New York.

Electroencephalographic (EEG) monitoring to indicate brain state during anesthesia has become widely available. It remains unclear whether EEG-guided anesthesia influences perioperative outcomes. The sixth Perioperative Quality Initiative (POQI-6) brought together an international team of multidisciplinary experts from anesthesiology, biomedical engineering, neurology, and surgery to review the current literature and to develop consensus recommendations on the utility of EEG monitoring during anesthesia. We retrieved a total of 1023 articles addressing the use of EEG monitoring during anesthesia and conducted meta-analyses from 15 trials to determine the effect of EEG-guided anesthesia on the rate of unintentional awareness, postoperative delirium, neurocognitive disorder, and long-term mortality after surgery. After considering current evidence, the working group recommends that EEG monitoring should be considered as part of the vital organ monitors to guide anesthetic management. In addition, we encourage anesthesiologists to be knowledgeable in basic EEG interpretation, such as raw waveform, spectrogram, and processed indices, when using these devices. Current evidence suggests that EEG-guided anesthesia reduces the rate of awareness during total intravenous anesthesia and has similar efficacy in preventing awareness as compared with end-tidal anesthetic gas monitoring. There is, however, insufficient evidence to recommend the use of EEG monitoring for preventing postoperative delirium, neurocognitive disorder, or postoperative mortality.
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http://dx.doi.org/10.1213/ANE.0000000000004502DOI Listing
May 2020

Effect of General Anesthetics on Caspase-3 Levels in Patients With Aneurysmal Subarachnoid Hemorrhage: A Preliminary Study.

J Neurosurg Anesthesiol 2021 Apr;33(2):172-176

Department of Anaesthesia and Intensive Care, Division of Neuroanesthesia.

Background: General anesthesia has been associated with neuronal apoptosis and activation of caspases. Apoptosis is a crucial factor in early brain injury following aneurysmal subarachnoid hemorrhage (aSAH). We conducted a double-blind, prospective, randomized pilot study to evaluate the effect of 4 anesthetic agents on cerebrospinal fluid (CSF) and serum caspase-3 levels in aSAH patients.

Materials And Methods: A total of 44 good-grade aSAH patients with preoperative lumbar drain scheduled for surgical clipping or endovascular coiling were randomized to receive maintenance of anesthesia with propofol, isoflurane, sevoflurane, or desflurane. Caspase-3 levels were measured in CSF and serum samples collected at baseline, 1 hour after induction, and 1 hour after cessation of anesthesia.

Results: Compared with baseline, there was a decrease in CSF caspase-3 levels and an increase in serum caspase-3 levels 1 hour after exposure to all 4 anesthetic agents; levels returned to baseline values after cessation of anesthesia. Median CSF caspase-3 levels at baseline, 1 hour after anesthesia exposure, and 1 hour after cessation of anesthesia were 0.0679, 0.0004, and 0.0689 ng/mL, respectively (P<0.05). Median serum caspase-3 levels at baseline, 1 hour after anesthesia exposure, and 1-hour after cessation of anesthesia were 0.0028, 0.0682, and 0.0044 ng/mL, respectively (P<0.05).

Conclusions: Propofol, isoflurane, sevoflurane, or desflurane have similar effects on CSF and serum caspase-3. The reduction of intraoperative CSF caspase-3 levels suggests a possible role for general anesthesia in neuroresuscitation by slowing the neuronal apoptotic pathway.
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http://dx.doi.org/10.1097/ANA.0000000000000648DOI Listing
April 2021

Chronic Calcineurin Inhibition via Cyclosporine A Impairs Visuospatial Learning After Isoflurane Anesthesia.

Anesth Analg 2019 07;129(1):192-203

From the Neuroanesthesia Laboratory, Atlanta Veterans Affairs Medical Center/Emory University, Atlanta, Georgia.

Background: Clinical studies implicate the perioperative period in cognitive complications, and increasing experimental evidence shows that the anesthetic agents can affect neuronal processes that underpin learning and memory. Calcineurin, a Ca-dependent phosphatase critically involved in synaptic plasticity, is activated after isoflurane exposure, but its role in the neurological response to anesthesia is unclear.

Methods: We investigated the effect of chronic calcineurin inhibition on postanesthetic cognitive function. Mice were treated with 30 minutes of isoflurane anesthesia during a chronic cyclosporine A regimen. Behavioral end points during the perianesthesia period were quantified. Visuospatial learning was assessed with the water radial arm maze. Total and biotinylated surface protein expression of the α5β3γ2 γ-aminobutyric acid (GABA) type A receptors was measured. Expression of the GABA synthesis enzyme glutamate decarboxylase (GAD)-67 was also measured.

Results: Mice treated with cyclosporine A before anesthesia showed significant deficits in visuospatial learning compared to sham and cyclosporine A-treated mice (n = 10 per group, P = .0152, Tukey post hoc test). Induction and emergence were unaltered by cyclosporine A. Analysis of hippocampal protein expression revealed an increased surface expression of the α5 GABA type A receptor subunit after isoflurane treatment (P = .019, Dunnett post hoc testing), as well as a decrease in GAD-67 expression. Cyclosporine A did not rescue either effect.

Conclusions: Our results confirm the work of others that isoflurane induces changes to inhibitory network function and exclude calcineurin inhibition via cyclosporine A as an intervention. Further, our studies suggest that calcineurin mediates a protective role in the neurological response to anesthesia, and patients receiving cyclosporine A may be an at-risk group for memory problems related to anesthesia.
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http://dx.doi.org/10.1213/ANE.0000000000004183DOI Listing
July 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

Sex effects on behavioral markers of emergence from propofol and isoflurane anesthesia in rats.

Behav Brain Res 2019 07 18;367:59-67. Epub 2019 Mar 18.

Neuroanesthesia Laboratory, Atlanta VA Medical Center/Emory University, Atlanta, GA, USA; Department of Anesthesiology, Emory University School of Medicine, Atlanta, GA, USA; Department of Anesthesiology, Columbia University Medical Center, New York, NY, USA. Electronic address:

Clinical studies have demonstrated sex-related differences in recovery from surgical anesthesia. This study aimed to characterize the emergence pattern following two anesthesia regimens in both sexes of rats. We considered six different markers of emergence from anesthesia: sigh, eye blinking, forelimb movement, mastication, neck extension, and recovery of the righting reflex (RORR). Spontaneous motor activity 24 h after the anesthesia induction was also examined. Our results showed that the rank order of the emergence latency after intraperitoneal propofol, PRO, exposure was forelimb movement < sigh < blink < mastication < neck extension < RORR, while after inhaled isoflurane, ISO, anesthesia the sequence was changed as sigh < blink < mastication < forelimb movement < neck extension < RORR in both male and female rats. Moreover, the latency to emergence after PRO in female rats was significantly higher than male rats, although following ISO there was no difference between the sexes (P < 0.001; P > 0.05, respectively). Open-field testing revealed no difference in PRO and ISO spontaneous locomotor activity due to drug administration (P > 0.05). These two anesthetics presented different emergence sequences. Although clinical data suggests that females arouse faster than males from anesthesia with propofol, our intraperitoneal technique in a rodent model had the opposite effect. Pharmacokinetic analysis demonstrated increased absorption of injected propofol for the female rats in our study, emphasizing the role of sexual dimorphism in drug distribution in rodents. Despite these pharmacokinetic differences, the pharmacodynamic effects of the drugs were remarkably consistent among both sexes through emergence.
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http://dx.doi.org/10.1016/j.bbr.2019.03.029DOI Listing
July 2019

Escape From Oblivion: Neural Mechanisms of Emergence From General Anesthesia.

Anesth Analg 2019 04;128(4):726-736

Department of Anesthesiology, Critical Care and Pain Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts.

The question of how general anesthetics suppress consciousness has persisted since the mid-19th century, but it is only relatively recently that the field has turned its focus to a systematic understanding of emergence. Once assumed to be a purely passive process, spontaneously occurring as residual levels of anesthetics dwindle below a critical value, emergence from general anesthesia has been reconsidered as an active and controllable process. Emergence is driven by mechanisms that can be distinct from entry to the anesthetized state. In this narrative review, we focus on the burgeoning scientific understanding of anesthetic emergence, summarizing current knowledge of the neurotransmitter, neuromodulators, and neuronal groups that prime the brain as it prepares for its journey back from oblivion. We also review evidence for possible strategies that may actively bias the brain back toward the wakeful state.
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http://dx.doi.org/10.1213/ANE.0000000000004006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6885009PMC
April 2019

A Preoperative Cognitive Screening Test Predicts Increased Length of Stay in a Frail Population: A Retrospective Case-Control Study.

Anesth Analg 2019 11;129(5):1283-1290

From the Department of Anesthesiology, Emory University School of Medicine, Atlanta, Georgia.

Background: Frailty is associated with adverse perioperative outcomes including major morbidity, mortality, and increased length of stay. We sought to elucidate the role that a preoperatively assessed Mini-Cog can play in assessing the risk of adverse perioperative outcomes in a population at high risk of frailty.

Methods: In this retrospective case-control study, patients who were >60 years of age, nonambulatory, or had >5 documented medications were preoperatively assessed for handgrip strength, walking speed, and Mini-Cog score. The Emory University Clinical Data Warehouse was then used to extract this information and other perioperative data elements and outcomes data.

Results: Data were available for 1132 patients undergoing a wide variety of surgical procedures. For the subset of 747 patients with data for observed-to-expected length of stay, an abnormal Mini-Cog was associated with an increased odds of observed-to-expected >1 (odds ratio, 1.52; 95% CI, 1.05-2.19; P = .025). There was no association of abnormal Mini-Cog with intensive care unit length of stay >3 days (P = .182) discharge to home with self-care (P = .873) or risk of readmission (P = .104). Decreased baseline hemoglobin was associated with increased risk of 2 of the 4 outcomes studied.

Conclusions: In a high-risk pool of patients, Mini-Cog may not be sensitive enough to detect significant differences for most adverse outcomes. Further work is needed to assess whether cognitive screens with greater resolution are of value in this context and to compare tools for assessing overall frailty status.
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http://dx.doi.org/10.1213/ANE.0000000000004103DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7877444PMC
November 2019

Understanding the Effects of General Anesthetics on Cortical Network Activity Using Ex Vivo Preparations.

Anesthesiology 2019 06;130(6):1049-1063

From the Department of Anaesthesia, Waikato District Health Board, Hamilton, New Zealand (L.J.V.) the Department of Anesthesiology, Emory University School of Medicine, Atlanta, Georgia (P.S.G) Anesthesiology and Research Divisions, Atlanta Veterans Administration Medical Center, Atlanta, Georgia (P.S.G.) the Experimental Anesthesiology Section, Department of Anesthesiology, University Hospital of Tübingen, Tübingen, Germany (H.H.) rthe Department of Anesthesiology, University of Wisconsin, Madison, Wisconsin (M.I.B.).

General anesthetics have been used to ablate consciousness during surgery for more than 150 yr. Despite significant advances in our understanding of their molecular-level pharmacologic effects, comparatively little is known about how anesthetics alter brain dynamics to cause unconsciousness. Consequently, while anesthesia practice is now routine and safe, there are many vagaries that remain unexplained. In this paper, the authors review the evidence that cortical network activity is particularly sensitive to general anesthetics, and suggest that disruption to communication in, and/or among, cortical brain regions is a common mechanism of anesthesia that ultimately produces loss of consciousness. The authors review data from acute brain slices and organotypic cultures showing that anesthetics with differing molecular mechanisms of action share in common the ability to impair neurophysiologic communication. While many questions remain, together, ex vivo and in vivo investigations suggest that a unified understanding of both clinical anesthesia and the neural basis of consciousness is attainable.
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http://dx.doi.org/10.1097/ALN.0000000000002554DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6520142PMC
June 2019

An update on postoperative delirium: Clinical features, neuropathogenesis, and perioperative management.

Curr Anesthesiol Rep 2018 07;8(3):252-262

Department of Anesthesiology, Emory University, Atlanta, GA, USA.

Purpose Of Review: We present a focused review on postoperative delirium for anesthesiologists, encompassing clinical features, neuropathogenesis, and clinical identification and management strategies based on risk factors and current delirium treatments.

Recent Findings: The literature on postoperative delirium is dominated by non-experimental studies. We review delirium phenotypes, diagnostic criteria, and present standard nomenclature based on current literature. Disruption of cortical integration of complex information (CICI) may provide a framework to understand the neuropathogenesis of postoperative delirium, as well as risk factors and clinical modifiers in the perioperative period. We further divide risk factors into patient factors, surgical factors, and medical/pharmacological factors, and present specific considerations for each in the preoperative, intraoperative, and postoperative periods.

Summary: Postoperative delirium is prevalent, poorly understood, and often missed with current screening techniques. Proper identification of risk factors is useful for perioperative interventions and can help tailor patient-specific management strategies.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6290904PMC
July 2018

Faster emergence behavior from ketamine/xylazine anesthesia with atipamezole versus yohimbine.

PLoS One 2018 29;13(10):e0199087. Epub 2018 Oct 29.

Atlanta VA Center for Visual and Neurocognitive Rehabilitation, Decatur, Georgia, United States of America.

Recent interest in reversal of the hypnotic effects of anesthesia has mainly focused on overcoming a surge in GABA-mediated inhibitory signaling through activation of subcortical arousal circuits or antagonizing GABA receptors. Here we examine the reversal of anesthesia produced from non-GABA agents ketamine/xylazine and the effects of antagonists of adrenoreceptors. These antagonists vary in selectivity and produce temporally unique waking behavior post-anesthesia. We compared two antagonists with differential selectivity for α1- vs. α2-receptors, yohimbine (YOH, 1:40 selectivity) and atipamezole (ATI, 1:8500). Adult mice received intraperitoneal injections of either YOH (4.3 mg/kg), ATI (0.4 mg/kg), or saline after achieving sustained loss of righting following injection of ketamine/xylazine (ketamine: 65.0 mg/kg; xylazine: 9.9 mg/kg). Behaviors indicative of the post-anesthesia, re-animation sequence were carefully monitored and the timing of each behavior relative to anesthesia induction was compared. Both YOH and ATI hastened behaviors indicative of emergence, but ATI was faster than YOH to produce certain behaviors, including whisker movement (YOH: 21.9±1.5 min, ATI: 17.5±0.5 min, p = 0.004) and return of righting reflex (RORR) (YOH: 40.6±8.8 min, ATI: 26.0±1.2 min, p<0.001). Interestingly, although YOH administration hastened early behavioral markers of emergence relative to saline (whisking), the completion of the emergence sequence (time from first marker to appearance of RORR) was delayed with YOH. We attribute this effect to antagonism of α1 receptors by yohimbine. Also notable was the failure of either antagonist to hasten the re-establishment of coordinated motor behavior (e.g., attempts to remove adhesive tape on the forepaw placed during anesthesia) relative to the end of emergence (RORR). In total, our work suggests that in addition to pharmacokinetic effects, re-establishment of normal waking behaviors after anesthesia involves neuronal circuits dependent on time and/or activity.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0199087PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6205597PMC
March 2019

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

Central Disorders of Hypersomnolence, Restless Legs Syndrome, and Surgery With General Anesthesia: Patient Perceptions.

Front Hum Neurosci 2018 20;12:99. Epub 2018 Mar 20.

Sleep Center and Department of Neurology, Emory University School of Medicine, Atlanta, GA, United States.

The importance of obstructive sleep apnea in patients undergoing surgery with general anesthesia is well-defined, but the surgical and anesthetic implications of other sleep disorders are less clear. We sought to evaluate response to surgery with general anesthesia in patients with central disorders of hypersomnolence or restless legs syndrome. We surveyed patients on their most recent surgical procedure with general anesthesia, querying about procedure, recovery, and any changes in sleep disorder symptomatology following the procedure. Forty-five patients with restless legs syndrome and 57 patients with central disorders of hypersomnolence (15 narcolepsy type 2, 1 narcolepsy type 1, 30 idiopathic hypersomnia, 1 Kleine-Levin syndrome, and 10 subjective sleepiness) completed the survey, with response rates of 45.5 and 53.8%, respectively. While patients in both groups were equally likely to report surgical complications and difficulty awakening from anesthesia, hypersomnolent patients were more likely to report worsened sleepiness (40% of the hypersomnolent group vs. 11% of the RLS group, = 0.001) and worsening of their sleep disorder symptoms (40% of the hypersomnolent group vs. 9% of the RLS group, = 0.0001). Patients with sleep disorders other than sleep apnea frequently report surgical or anesthetic complications. Patients with hypersomnolence disorders commonly perceive that their sleep disorder worsened following a procedure; whether this might be related to long term effects of general anesthesia in a particularly vulnerable clinical population requires further study.
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http://dx.doi.org/10.3389/fnhum.2018.00099DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5869929PMC
March 2018

Influences of 12-Week Physical Activity Interventions on TMS Measures of Cortical Network Inhibition and Upper Extremity Motor Performance in Older Adults-A Feasibility Study.

Front Aging Neurosci 2017 4;9:422. Epub 2018 Jan 4.

VA Rehabilitation R&D Center for Visual and Neurocognitive Rehabilitation, Atlanta VA Medical Center, Decatur, GA, United States.

Data from previous cross-sectional studies have shown that an increased level of physical fitness is associated with improved motor dexterity across the lifespan. In addition, physical fitness is positively associated with increased laterality of cortical function during unimanual tasks; indicating that sedentary aging is associated with a loss of interhemispheric inhibition affecting motor performance. The present study employed exercise interventions in previously sedentary older adults to compare motor dexterity and measure of interhemispheric inhibition using transcranial magnetic stimulation (TMS) after the interventions. Twenty-one community-dwelling, reportedly sedentary older adults were recruited, randomized and enrolled to a 12-week aerobic exercise group or a 12-week non-aerobic exercise balance condition. The aerobic condition was comprised of an interval-based cycling "spin" activity, while the non-aerobic "balance" exercise condition involved balance and stretching activities. Participants completed upper extremity dexterity batteries and estimates of VOmax in addition to undergoing single (ipsilateral silent period-iSP) and paired-pulse interhemispheric inhibition (ppIHI) in separate assessment sessions before and after study interventions. After each intervention during which heart rate was continuously recorded to measure exertion level (load), participants crossed over into the alternate arm of the study for an additional 12-week intervention period in an AB/BA design with no washout period. After the interventions, regardless of intervention order, participants in the aerobic spin condition showed higher estimated VOmax levels after the 12-week intervention as compared to estimated VOmax in the non-aerobic balance intervention. After controlling for carryover effects due to the study design, participants in the spin condition showed longer iSP duration than the balance condition. Heart rate load was more strongly correlated with silent period duration after the Spin condition than estimated VO. Aging-related changes in cortical inhibition may be influenced by 12-week physical activity interventions when assessed with the iSP. Although inhibitory signaling is mediates both ppIHI and iSP measures each TMS modality likely employs distinct inhibitory networks, potentially differentially affected by aging. Changes in inhibitory function after physical activity interventions may be associated with improved dexterity and motor control at least as evidence from this feasibility study show.
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http://dx.doi.org/10.3389/fnagi.2017.00422DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5758495PMC
January 2018

Propofol and Sevoflurane Differentially Modulate Cortical Depolarization following Electric Stimulation of the Ventrobasal Thalamus.

Front Comput Neurosci 2017 11;11:109. Epub 2017 Dec 11.

Department of Anesthesiology, Klinikum rechts der Isar, Technische Universität München, Munich, Germany.

The neuronal mechanisms how anesthetics lead to loss of consciousness are unclear. Thalamocortical interactions are crucially involved in conscious perception; hence the thalamocortical network might be a promising target for anesthetic modulation of neuronal information pertaining to arousal and waking behavior. General anesthetics affect the neurophysiology of the thalamus and the cortex but the exact mechanisms of how anesthetics interfere with processing thalamocortical information remain to be elucidated. Here we investigated the effect of the anesthetic agents sevoflurane and propofol on thalamocortical network activity . We used voltage-sensitive dye imaging techniques to analyze the cortical depolarization in response to stimulation of the thalamic ventrobasal nucleus in brain slices from mice. Exposure to sevoflurane globally decreased cortical depolarization in a dose-dependent manner. Sevoflurane reduced the intensity and extent of cortical depolarization and delayed thalamocortical signal propagation. In contrast, propofol neither affected area nor amplitude of cortical depolarization. However, propofol exposure resulted in regional changes in spatial distribution of maximum fluorescence intensity in deep regions of the cortex. In summary, our experiments revealed substance-specific effects on the thalamocortical network. Functional changes of the neuronal network are known to be pivotally involved in the anesthetic-induced loss of consciousness. Our findings provide further evidence that the mechanisms of anesthetic-mediated loss of consciousness are drug- and pathway-specific.
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http://dx.doi.org/10.3389/fncom.2017.00109DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5732174PMC
December 2017