George A Mashour

University of Washington Seattle, Seattle, Washington, United States

Are you George A Mashour?

Claim your profile

Publications (156)816.98 Total impact

  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Sleep, anesthesia and coma share a number of neural features but the recovery profiles are radically different. To understand the mechanisms of reversibility of unconsciousness at the network level, we studied the conditions for gradual and abrupt state transitions in conscious and anesthetized states. We hypothesized that the conditions for explosive synchronization (ES) in human brain networks would be present in the anesthetized brain just over the threshold of unconsciousness. To test this hypothesis, functional brain networks were constructed from multi-channel electroencephalogram (EEG) recordings in seven healthy subjects across conscious, unconscious, and recovery states. We analyzed four conditions that were previously reported as conditions for ES in generic, non-biological networks: (1) correlation between node degree and frequency, (2) disassortativity (i.e., the tendency of highly-connected nodes to link with less-connected nodes, or vice versa), (3) frequency difference of coupled nodes, and (4) an inequality relationship for ES between local and global network properties, which is referred to as the suppressive rule. We observed that the four network conditions for ES were satisfied in the unconscious state. Conditions for ES in the human brain suggest a potential mechanism for rapid recovery from the lightly-anesthetized state. This study demonstrates for the first time that the network conditions for ES, formerly shown in generic networks only, are present in empirically-derived functional brain networks. Further investigations with deep anesthesia, sleep, and coma could provide insight into the underlying causes of variability in recovery profiles of these unconscious states.
    Full-text · Article · Jan 2016 · Frontiers in Computational Neuroscience
  • Source

    Preview · Article · Dec 2015 · BMC Neuroscience
  • [Show abstract] [Hide abstract]
    ABSTRACT: Background: Beach chair positioning during general anesthesia is associated with cerebral oxygen desaturation. Changes in cerebral oxygenation resulting from the interaction of inspired oxygen fraction (Fio2), end-tidal carbon dioxide (PETco2), and anesthetic choice have not been fully evaluated in anesthetized patients in the beach chair position. Methods: This is a prospective interventional within-group study of patients undergoing shoulder surgery in the beach chair position that incorporated a randomized comparison between two anesthetics. Fifty-six patients were randomized to receive desflurane or total intravenous anesthesia with propofol. Following induction of anesthesia and positioning, Fio2 and minute ventilation were sequentially adjusted for all patients. Regional cerebral oxygenation (rSo2) was the primary outcome and was recorded at each of five set points. Results: While maintaining Fio2 at 0.3 and PETco2 at 30 mmHg, there was a decrease in rSo2 from 68% (SD, 12) to 61% (SD, 12) (P < 0.001) following beach chair positioning. The combined interventions of increasing Fio2 to 1.0 and increasing PETco2 to 45 mmHg resulted in a 14% point improvement in rSo2 to 75% (SD, 12) (P <0.001) for patients anesthetized in the beach chair position. There was no significant interaction effect of the anesthetic at the study intervention points. Conclusions: Increasing Fio2 and PETco2 resulted in a significant increase in rSo2 that overcomes desaturation in patients anesthetized in the beach chair position and that appears independent of anesthetic choice.
    No preview · Article · Oct 2015 · Anesthesiology
  • Phillip Vlisides · George A Mashour
    [Show abstract] [Hide abstract]
    ABSTRACT: Purpose: Perioperative stroke is associated with significant morbidity and mortality, with an incidence that may be underappreciated. In this review, we examine the significance, pathophysiology, risk factors, and evidence-based recommendations for the prevention and management of perioperative stroke. Source: This is a narrative review based on literature from the PubMed database regarding perioperative stroke across a broad surgical population. The Society for Neuroscience in Anesthesiology and Critical Care recently published evidence-based recommendations for perioperative management of patients at high risk for stroke; these recommendations were analyzed and incorporated into this review. Principal findings: The incidence of overt perioperative stroke is highest in patients presenting for cardiac and major vascular surgery, although preliminary data suggest that the incidence of covert stroke may be as high as 10% in non-cardiac surgery patients. The pathophysiology of perioperative stroke involves different pathways. Thrombotic stroke can result from increased inflammation and hypercoagulability; cardioembolic stroke can result from disease states such as atrial fibrillation, and tissue hypoxia from anemia can result from the combination of anemia and beta-blockade. Across large-scale database studies, common risk factors for perioperative stroke include advanced age, history of cerebrovascular disease, ischemic heart disease, congestive heart failure, atrial fibrillation, and renal disease. Recommendations for prevention and management of perioperative stroke are evolving, though further work is needed to clarify the role of proposed modifiable risk factors such as perioperative anticoagulation, antiplatelet therapy, appropriate transfusion thresholds, and perioperative beta-blockade. Conclusions: Perioperative stroke carries a significant clinical burden. The incidence of perioperative stroke may be higher than previously recognized, and there are diverse pathophysiologic mechanisms. There are many opportunities for further investigation of the pathophysiology, prevention, and management of perioperative stroke.
    No preview · Article · Sep 2015 · Canadian Anaesthetists? Society Journal
  • Vijay Tarnal · Phillip E Vlisides · George A Mashour
    [Show abstract] [Hide abstract]
    ABSTRACT: Achieving a smooth and rapid emergence from general anesthesia is of particular importance for neurosurgical patients and is a clinical goal for neuroanesthesiologists. Recent data suggest that the process of emergence is not simply the mirror image of induction, but rather controlled by distinct neural circuits. In this narrative review, we discuss (1) hysteresis, (2) the concept of neural inertia, (3) the asymmetry between the neurobiology of induction and emergence, and (4) recent attempts at actively inducing emergence.
    No preview · Article · Aug 2015 · Journal of neurosurgical anesthesiology
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Nav1.6 is a major voltage-gated sodium channel in the central and peripheral nervous systems. Within neurons, the channel protein is concentrated at the axon initial segment and nodes of Ranvier, where it functions in initiation and propagation of action potentials. We examined the role of Nav1.6 in general anesthesia using two mouse mutants with reduced activity of Nav1.6, Scn8amedJ/medJ and Scn8a9J/9J. The mice were exposed to the general anesthetics isoflurane and sevoflurane in step-wise increments; the concentration required to produce loss of righting reflex, a surrogate for anesthetic-induced unconsciousness in rodents, was determined. Mice homozygous for these mutations exhibited increased sensitivity to both isoflurane and sevoflurane. The increased sensitivity was observed during induction of unconsciousness but not during the recovery phase, suggesting that the effect is not attributable to compromised systemic physiology. Electroencephalographic theta power during baseline waking was lower in mutants, suggesting decreased arousal and reduced neuronal excitability. This is the first report linking reduced activity of a specific voltage-gated sodium channel to increased sensitivity to general anesthetics in vivo.
    Preview · Article · Aug 2015 · PLoS ONE
  • [Show abstract] [Hide abstract]
    ABSTRACT: Beach chair positioning during general anesthesia is associated with cerebral oxygen desaturation. Changes in cerebral oxygenation resulting from the interaction of inspired oxygen fraction (FIO2), end-tidal carbon dioxide (PETCO2), and anesthetic choice have not been fully evaluated in anesthetized patients in the beach chair position. This is a prospective interventional within-group study of patients undergoing shoulder surgery in the beach chair position that incorporated a randomized comparison between two anesthetics. Fifty-six patients were randomized to receive desflurane or total intravenous anesthesia with propofol. Following induction of anesthesia and positioning, FIO2 and minute ventilation were sequentially adjusted for all patients. Regional cerebral oxygenation (rSO2) was the primary outcome and was recorded at each of five set points. While maintaining FIO2 at 0.3 and PETCO2 at 30 mmHg, there was a decrease in rSO2 from 68% (SD, 12) to 61% (SD, 12) (P < 0.001) following beach chair positioning. The combined interventions of increasing FIO2 to 1.0 and increasing PETCO2 to 45 mmHg resulted in a 14% point improvement in rSO2 to 75% (SD, 12) (P <0.001) for patients anesthetized in the beach chair position. There was no significant interaction effect of the anesthetic at the study intervention points. Increasing FIO2 and PETCO2 resulted in a significant increase in rSO2 that overcomes desaturation in patients anesthetized in the beach chair position and that appears independent of anesthetic choice.
    No preview · Article · Aug 2015 · Anesthesiology
  • [Show abstract] [Hide abstract]
    ABSTRACT: Awareness during general anaesthesia is a source of concern for patients and anaesthetists, with potential for psychological and medicolegal sequelae. We used a registry to evaluate unintended awareness from the patient's perspective with an emphasis on their experiences and healthcare provider responses. English-speaking subjects self-reported explicit recall of events during anaesthesia to the Anesthesia Awareness Registry of the ASA, completed a survey, and submitted copies of medical records. Anaesthesia awareness was defined as explicit recall of events during induction or maintenance of general anaesthesia. Patient experiences, satisfaction, and desired practitioner responses to explicit recall were based on survey responses. Most of the 68 respondents meeting inclusion criteria (75%) were dissatisfied with the manner in which their concerns were addressed by their healthcare providers, and many reported long-term harm. Half (51%) of respondents reported that neither the anaesthesia provider nor surgeon expressed concern about their experience. Few were offered an apology (10%) or referral for counseling (15%). Patient preferences for responses after an awareness episode included validation of their experience (37%), an explanation (28%), and discussion or follow-up to the episode (26%). Data from this registry confirm the serious impact of anaesthesia awareness for some patients, and suggest that patients need more systematic responses and follow-up by healthcare providers. © The Author 2015. Published by Oxford University Press on behalf of the British Journal of Anaesthesia. All rights reserved. For Permissions, please email: journals.permissions@oup.com.
    No preview · Article · Jul 2015 · BJA British Journal of Anaesthesia
  • Source

    Preview · Article · Jul 2015 · BJA British Journal of Anaesthesia
  • [Show abstract] [Hide abstract]
    ABSTRACT: There is limited understanding of cortical neurochemistry and cortical connectivity during ketamine anaesthesia. We conducted a systematic study to investigate the effects of ketamine on cortical acetylcholine (ACh) and electroencephalographic coherence. Male Sprague-Dawley rats (n=11) were implanted with electrodes to record electroencephalogram (EEG) from frontal, parietal, and occipital cortices, and with a microdialysis guide cannula for simultaneous measurement of ACh concentrations in prefrontal cortex before, during, and after ketamine anaesthesia. Coherence and power spectral density computed from the EEG, and ACh concentrations, were compared between conscious and unconscious states. Loss of righting reflex was used as a surrogate for unconsciousness. Ketamine-induced unconsciousness was associated with a global reduction of power (P=0.02) in higher gamma bandwidths (>65 Hz), a global reduction of coherence (P≤0.01) across a broad frequency range (0.5-250 Hz), and a significant increase in ACh concentrations (P=0.01) in the prefrontal cortex. Compared with the unconscious state, recovery of righting reflex was marked by a further increase in ACh concentrations (P=0.0007), global increases in power in theta (4-10 Hz; P=0.03) and low gamma frequencies (25-55 Hz; P=0.0001), and increase in power (P≤0.01) and coherence (P≤0.002) in higher gamma frequencies (65-250 Hz). Acetylcholine concentrations, coherence, and spectral properties returned to baseline levels after a prolonged recovery period. Ketamine-induced unconsciousness is characterized by suppression of high-frequency gamma activity and a breakdown of cortical coherence, despite increased cholinergic tone in the cortex. © The Author 2015. Published by Oxford University Press on behalf of the British Journal of Anaesthesia. All rights reserved. For Permissions, please email: journals.permissions@oup.com.
    No preview · Article · May 2015 · BJA British Journal of Anaesthesia
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Author Summary Current brain connectome projects are attempting to construct a map of the structural and functional network connections in the brain. One goal of these projects is to understand how network organization determines local functions and information transfer patterns, which is essential to achieve higher cognitive brain functions. Because of the limitation of constructing all brain maps for all cognitive states, finding a general relationship of global topology, local dynamics and the directionality of information transfer in a network is crucial. In this study, we show that inter-node directionality arises naturally from the topology of the network. Analytical, computational, and empirical results all demonstrate that network nodes with more connections (i.e., higher degree) lag in phase, while lower-degree nodes lead. Our mathematical analysis allowed us to predict the directionality patterns in general model networks as well as human brain networks across different states of consciousness. These findings may provide more straightforward approaches to dissecting how directionality between interacting nodes is shaped in complex brain networks, providing a foundation for understanding principles of information transfer. Furthermore, the underlying mathematical relationship between node connections and directionality patterns has the potential to advance network science across numerous disciplines.
    Full-text · Article · Apr 2015 · PLoS Computational Biology
  • Source
    G A Mashour · M S Avidan
    [Show abstract] [Hide abstract]
    ABSTRACT: Intraoperative awareness, with or without recall, continues to be a topic of clinical significance and neurobiological interest. In this article, we review evidence pertaining to the incidence, sequelae, and prevention of intraoperative awareness. We also asses which aspects of the complication are well understood (i.e. non-controversial) and which require further research for clarification (i.e. controversial). © The Author 2015. Published by Oxford University Press on behalf of the British Journal of Anaesthesia. All rights reserved. For Permissions, please email: journals.permissions@oup.com.
    Preview · Article · Mar 2015 · BJA British Journal of Anaesthesia
  • R D Sanders · M E Jørgensen · G A Mashour

    No preview · Article · Feb 2015 · BJA British Journal of Anaesthesia
  • [Show abstract] [Hide abstract]
    ABSTRACT: The red-hair phenotype, which is often produced by mutations in the melanocortin-1 receptor gene, has been associated with an increase in sedative, anesthetic, and analgesic requirements in both animal and human studies. Nevertheless, the clinical implications of this phenomenon in red-haired patients undergoing surgery are currently unknown. In a secondary analysis of a prospective trial of intraoperative awareness, red-haired patients were identified and matched with five control patients, and the relative risk for intraoperative awareness was determined. Overall anesthetic management between groups was compared using Hotelling's T(2) statistic. Inhaled anesthetic requirements were compared between cohorts by evaluating the relationship between end-tidal anesthetic concentration and the bispectral index with a linear mixed-effects model. Time to recovery was compared using Kaplan-Meier analysis, and differences in postoperative pain and nausea/vomiting were evaluated with Chi square tests. A cohort of 319 red-haired patients was matched with 1,595 control patients for a sample size of 1,914. There were no significant differences in the relative risk of intraoperative awareness (relative risk = 1.67; 95% confidence interval 0.34 to 8.22), anesthetic management, recovery times, or postoperative pain between red-haired patients and control patients. The relationship between pharmacokinetically stable volatile anesthetic concentrations and bispectral index values differed significantly between red-haired patients and controls (P < 0.001), but without clinical implications. There were no demonstrable differences between red-haired patients and controls in response to anesthetic and analgesic agents or in recovery parameters. These findings suggest that perioperative anesthetic and analgesic management should not be altered based on self-reported red-hair phenotype.
    No preview · Article · Feb 2015 · Canadian Journal of Anaesthesia
  • Source
    UnCheol Lee · Stefanie Blain-Moraes · George A Mashour
    [Show abstract] [Hide abstract]
    ABSTRACT: 'Covert consciousness' is a state in which consciousness is present without the capacity for behavioural response, and it can occur in patients with intraoperative awareness or unresponsive wakefulness syndrome. To detect and prevent this undesirable state, it is critical to develop a reliable neurobiological assessment of an individual's level of consciousness that is independent of behaviour. One such approach that shows potential is measuring surrogates of cortical communication in the brain using electroencephalography (EEG). EEG is practicable in clinical application, but involves many fundamental signal processing problems, including signal-to-noise ratio and high dimensional complexity. Symbolic analysis of EEG can mitigate these problems, improving the measurement of brain connectivity and the ability to successfully assess levels of consciousness. In this article, we review the problem of covert consciousness, basic neurobiological principles of consciousness, current methods of measuring brain connectivity and the advantages of symbolic processing, with a focus on symbolic transfer entropy (STE). Finally, we discuss recent advances and clinical applications of STE and other symbolic analyses to assess levels of consciousness. © 2014 The Author(s) Published by the Royal Society. All rights reserved.
    Full-text · Article · Feb 2015 · Philosophical Transactions of The Royal Society A Mathematical Physical and Engineering Sciences
  • Source

    Full-text · Article · Jan 2015 · Canadian Journal of Anaesthesia
  • [Show abstract] [Hide abstract]
    ABSTRACT: BACKGROUND: Elective surgery can have long-term psychological sequelae, especially for patients who experience intraoperative awareness. However, risk factors, other than awareness, for symptoms of posttraumatic stress disorder (PTSD) after surgery are poorly defined, and practical screening methods have not been applied to a broad population of surgical patients. METHODS: The Psychological Sequelae of Surgery study was a prospective cohort study of patients previously enrolled in the United States and Canada in 3 trials for the prevention of intraoperative awareness. The 68 patients who experienced definite or possible awareness were matched with 418 patients who denied awareness based on age, sex, surgery type, and awareness risk. Participants completed the PTSD Checklist-Specific (PCL-S) and/or a modified Mini-International Neuropsychiatric Interview telephone assessment to identify symptoms of PTSD and symptom complexes consistent with a PTSD diagnosis. We then used structural equation modeling to produce a composite PTSD score and examined potential risk factors. RESULTS: One hundred forty patients were unreachable; of those contacted, 303 (88%) participated a median of 2 years postoperatively. Forty-four of the 219 patients (20.1%) who completed the PCL-S exceeded the civilian screening cutoff score for PTSD symptoms resulting from their surgery (15 of 35 [43%] with awareness and 29 of 184 [16%] without). Nineteen patients (8.7%; 5 of 35 [14%] with awareness and 14 of 184 [7.6%] without) both exceeded the cutoff and endorsed a breadth of symptoms consistent with the Diagnostic and Statistical Manual Fourth Edition diagnosis of PTSD attributable to their surgery. Factors independently associated with PTSD symptoms were poor social support, previous PTSD symptoms, previous mental health treatment, dissociation related to surgery, perceiving that one's life was threatened during surgery, and intraoperative awareness (all P <= 0.017). Perioperative dissociation was identified as a potential mediator for perioperative PTSD symptoms. CONCLUSIONS: Events in the perioperative period can precipitate psychological symptoms consistent with subsyndromal and syndromal PTSD. We not only confirmed the high rate of postoperative PTSD in awareness patients but also identified a significant rate in matched nonawareness controls. Screening surgical patients, especially those with potentially mediating risk factors such as intraoperative awareness or perioperative dissociation, for postoperative PTSD symptoms with the PCL-S is practical and could promote early referral, evaluation, and treatment.
    No preview · Article · Nov 2014 · Anesthesia & Analgesia
  • Michael S Avidan · George A Mashour

    No preview · Article · Nov 2014 · Anesthesia & Analgesia
  • [Show abstract] [Hide abstract]
    ABSTRACT: Background: Recent studies of anesthetic-induced unconsciousness in humans have focused predominantly on the intravenous drug propofol and have identified anterior dominance of alpha rhythms and frontal phase-amplitude coupling patterns as neurophysiological markers. However, it is unclear whether the correlates of propofol-induced unconsciousness are generalizable to inhaled anesthetics, which have distinct molecular targets and which are used more commonly in clinical practice. Methods: The authors recorded 64-channel electroencephalograms in healthy human participants during consciousness, sevoflurane-induced unconsciousness, and recovery (n = 10; n = 7 suitable for analysis). Spectrograms and scalp distributions of low-frequency (1 Hz) and alpha (10 Hz) power were analyzed, and phase-amplitude modulation between these two frequencies was calculated in frontal and parietal regions. Phase lag index was used to assess phase relationships across the cortex. Results: At concentrations sufficient for unconsciousness, sevoflurane did not result in a consistent anteriorization of alpha power; the relationship between low-frequency phase and alpha amplitude in the frontal cortex did not undergo characteristic transitions. By contrast, there was significant cross-frequency coupling in the parietal region during consciousness that was not observed after loss of consciousness. Furthermore, a reversible disruption of anterior-posterior phase relationships in the alpha bandwidth was identified as a correlate of sevoflurane-induced unconsciousness. Conclusion: In humans, sevoflurane-induced unconsciousness is not correlated with anteriorization of alpha and related cross-frequency patterns, but rather by a disruption of phase-amplitude coupling in the parietal region and phase-phase relationships across the cortex.
    No preview · Article · Oct 2014 · Anesthesiology
  • [Show abstract] [Hide abstract]
    ABSTRACT: Perioperative stroke can be a catastrophic outcome for surgical patients and is associated with increased morbidity and mortality. This consensus statement from the Society for Neuroscience in Anesthesiology and Critical Care provides evidence-based recommendations and opinions regarding the 'preoperative, intraoperative, and postoperative care of patients at high risk for the complication.
    No preview · Article · Oct 2014 · Journal of Neurosurgical Anesthesiology

Publication Stats

2k Citations
816.98 Total Impact Points

Institutions

  • 2015
    • University of Washington Seattle
      Seattle, Washington, United States
  • 2007-2015
    • University of Michigan
      • • Department of Anesthesiology
      • • Medical School
      Ann Arbor, Michigan, United States
  • 2014
    • University of Kansas
      Lawrence, Kansas, United States
  • 2007-2014
    • Concordia University–Ann Arbor
      Ann Arbor, Michigan, United States
  • 2013
    • Washington University in St. Louis
      San Luis, Missouri, United States
  • 2004-2007
    • Harvard Medical School
      Boston, Massachusetts, United States
    • Humboldt-Universität zu Berlin
      Berlín, Berlin, Germany
  • 2006
    • Harvard University
      Cambridge, Massachusetts, United States
  • 2005
    • Massachusetts General Hospital
      • Department of Neurosurgery
      Boston, Massachusetts, United States
  • 1998-2001
    • Georgetown University
      • Department of Neurosurgery
      Washington, Washington, D.C., United States