George A Mashour

University of Kansas, Lawrence, Kansas, United States

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Publications (133)651.4 Total impact

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    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.
    Anesthesia & Analgesia 11/2014; · 3.30 Impact Factor
  • Michael S Avidan, George A Mashour
    Anesthesia and analgesia. 11/2014; 119(5):1022-1025.
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    ABSTRACT: 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.
    Anesthesiology 10/2014; · 5.16 Impact Factor
  • G A Mashour, D T Woodrum, M S Avidan
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    ABSTRACT: Summary Injury to the central and peripheral nervous systems is often permanent. As such, adverse neurological outcomes of surgery and anaesthesia can be devastating for patients and their families. In this article, we review the incidence, risk factors, outcomes, prevention, and treatment of a number of important neurological complications in the perioperative period.
    BJA British Journal of Anaesthesia 09/2014; · 4.24 Impact Factor
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    ABSTRACT: Intraoperative awareness with explicit recall is a potentially devastating complication of surgery that has been attributed to low anaesthetic concentrations in the vast majority of cases. Past studies have proposed the determination of an adequate dose for general anaesthetics that could be used to alert providers of potentially insufficient anaesthesia. However, there have been no systematic analyses of appropriate thresholds to develop population-based alerting algorithms for preventing intraoperative awareness.
    European journal of anaesthesiology. 07/2014;
  • George A Mashour, Michael S Avidan
    Anesthesia and analgesia. 07/2014; 119(1):1-3.
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    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.
    Journal of neurosurgical anesthesiology. 06/2014;
  • George A Mashour, Michael S Avidan
    Anesthesiology 06/2014; · 5.16 Impact Factor
  • George A Mashour, Michael S Avidan
    Canadian Anaesthetists? Society Journal 04/2014; · 2.31 Impact Factor
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    ABSTRACT: Postoperative delirium in the intensive care unit (ICU) is a frequent complication after cardiac or thoracic surgery and is associated with increased morbidity and mortality. In this single-center substudy of the BAG-RECALL trial (NCT00682825), we screened patients after cardiac or thoracic surgery in the ICU twice daily for delirium using the Confusion Assessment Method for the ICU. The primary outcome was the incidence of delirium in patients who had been randomized to intraoperative Bispectral Index (BIS)-guided and end-tidal anesthetic concentration-guided depth of anesthesia protocols. As a secondary analysis, a Bayesian stochastic search variable selection strategy was used to rank a field of candidate risk factors for delirium, followed by binary logistic regression. Of 310 patients assessed, 28 of 149 (18.8%) in the BIS group and 45 of 161 (28.0%) in the end-tidal anesthetic concentration group developed postoperative delirium in the ICU (odds ratio 0.60, 95% confidence interval, 0.35-1.02, P= 0.058). Low average volatile anesthetic dose, intraoperative transfusion, ASA physical status, and European System for Cardiac Operative Risk Evaluation were identified as independent predictors of delirium. A larger randomized study should determine whether brain monitoring with BIS or an alternative method decreases delirium after cardiac or thoracic surgery. The association between low anesthetic concentration and delirium is a surprising finding and could reflect that patients with poor health are both more sensitive to the effects of volatile anesthetic drugs and are also more likely to develop postoperative delirium. Investigation of candidate methods to prevent delirium should be prioritized in view of the established association between postoperative delirium and adverse patient outcomes.
    Anesthesia and analgesia 01/2014; · 3.08 Impact Factor
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    ABSTRACT: Recent studies of propofol-induced unconsciousness have identified characteristic properties of electroencephalographic alpha rhythms that may be mediated by drug activity at γ-aminobutyric acid (GABA) receptors in the thalamus. However, the effect of ketamine (a primarily non-GABAergic anesthetic drug) on alpha oscillations has not been systematically evaluated. We analyzed the electroencephalogram of 28 surgical patients during consciousness and ketamine-induced unconsciousness with a focus on frontal power, frontal cross-frequency coupling, frontal-parietal functional connectivity (measured by coherence and phase lag index), and frontal-to-parietal directional connectivity (measured by directed phase lag index) in the alpha bandwidth. Unlike past studies of propofol, ketamine-induced unconsciousness was not associated with increases in the power of frontal alpha rhythms, characteristic cross-frequency coupling patterns of frontal alpha power and slow-oscillation phase, or decreases in coherence in the alpha bandwidth. Like past studies of propofol using undirected and directed phase lag index, ketamine reduced frontal-parietal (functional) and frontal-to-parietal (directional) connectivity in the alpha bandwidth. These results suggest that directional connectivity changes in the alpha bandwidth may be state-related markers of unconsciousness induced by both GABAergic and non-GABAergic anesthetics.
    Frontiers in Systems Neuroscience 01/2014; 8:114.
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    ABSTRACT: Postoperative delirium is one of the most common complications of major surgery, affecting 10-70% of surgical patients 60 years and older. Delirium is an acute change in cognition that manifests as poor attention and illogical thinking and is associated with longer intensive care unit (ICU) and hospital stay, long-lasting cognitive deterioration and increased mortality. Ketamine has been used as an anaesthetic drug for over 50 years and has an established safety record. Recent research suggests that, in addition to preventing acute postoperative pain, a subanaesthetic dose of intraoperative ketamine could decrease the incidence of postoperative delirium as well as other neurological and psychiatric outcomes. However, these proposed benefits of ketamine have not been tested in a large clinical trial.
    BMJ Open 01/2014; 4(9):e005651. · 2.06 Impact Factor
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    Justin R Dunmyre, George A Mashour, Victoria Booth
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    ABSTRACT: Recent experimental studies investigating the neuronal regulation of rapid eye movement (REM) sleep have identified mutually inhibitory synaptic projections among REM sleep-promoting (REM-on) and REM sleep-inhibiting (REM-off) neuronal populations that act to maintain the REM sleep state and control its onset and offset. The control mechanism of mutually inhibitory synaptic interactions mirrors the proposed flip-flop switch for sleep-wake regulation consisting of mutually inhibitory synaptic projections between wake- and sleep-promoting neuronal populations. While a number of synaptic projections have been identified between these REM-on/REM-off populations and wake/sleep-promoting populations, the specific interactions that govern behavioral state transitions have not been completely determined. Using a minimal mathematical model, we investigated behavioral state transition dynamics dictated by a system of coupled flip-flops, one to control transitions between wake and sleep states, and another to control transitions into and out of REM sleep. The model describes the neurotransmitter-mediated inhibitory interactions between a wake- and sleep-promoting population, and between a REM-on and REM-off population. We proposed interactions between the wake/sleep and REM-on/REM-off flip-flops to replicate the behavioral state statistics and probabilities of behavioral state transitions measured from experimental recordings of rat sleep under ad libitum conditions and after 24 h of REM sleep deprivation. Reliable transitions from REM sleep to wake, as dictated by the data, indicated the necessity of an excitatory projection from the REM-on population to the wake-promoting population. To replicate the increase in REM-wake-REM transitions observed after 24 h REM sleep deprivation required that this excitatory projection promote transient activation of the wake-promoting population. Obtaining the reliable wake-nonREM sleep transitions observed in the data required that activity of the wake-promoting population modulated the interaction between the REM-on and REM-off populations. This analysis suggests neuronal processes to be targeted in further experimental studies of the regulatory mechanisms of REM sleep.
    PLoS ONE 01/2014; 9(4):e94481. · 3.53 Impact Factor
  • George A Mashour
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    ABSTRACT: The question of how structurally and pharmacologically diverse general anesthetics disrupt consciousness has persisted since the nineteenth century. There has traditionally been a significant focus on "bottom-up" mechanisms of anesthetic action, in terms of sensory processing, arousal systems, and structural scales. However, recent evidence suggests that the neural mechanisms of anesthetic-induced unconsciousness may involve a "top-down" process, which parallels current perspectives on the neurobiology of conscious experience itself. This article considers various arguments for top-down mechanisms of anesthetic-induced unconsciousness, with a focus on sensory processing and sleep-wake networks. Furthermore, recent theoretical work is discussed to highlight the possibility that top-down explanations may be causally sufficient, even assuming critical bottom-up events.
    Frontiers in Systems Neuroscience 01/2014; 8:115.
  • Jimo Borjigin, Michael M Wang, George A Mashour
    Proceedings of the National Academy of Sciences 11/2013; 110(47):E4406. · 9.81 Impact Factor
  • Jimo Borjigin, Michael M Wang, George A Mashour
    Proceedings of the National Academy of Sciences 10/2013; 110(44):E4124. · 9.81 Impact Factor
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    ABSTRACT: Patients with a history of intraoperative awareness with explicit recall (AWR) are hypothesized to be at higher risk for AWR than the general surgical population. In this study, the authors assessed whether patients with a history of AWR (1) are actually at higher risk for AWR; (2) receive different anesthetic management; and (3) are relatively resistant to the hypnotic actions of volatile anesthetics. Patients with a history of AWR and matched controls from three randomized clinical trials investigating prevention of AWR were compared for relative risk of AWR. Anesthetic management was compared with the use of the Hotelling's T statistic. A linear mixed model, including previously identified covariates, assessed the effects of a history of AWR on the relationship between end-tidal anesthetic concentration and bispectral index. The incidence of AWR was 1.7% (4 of 241) in patients with a history of AWR and 0.3% (4 of 1,205) in control patients (relative risk = 5.0; 95% CI, 1.3-19.9). Anesthetic management did not differ between cohorts, but there was a significant effect of a history of AWR on the end-tidal anesthetic concentration versus bispectral index relationship. Surgical patients with a history of AWR are five times more likely to experience AWR than similar patients without a history of AWR. Further consideration should be given to modifying perioperative care and postoperative evaluation of patients with a history of AWR.
    Anesthesiology 10/2013; · 5.16 Impact Factor
  • George A Mashour
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    ABSTRACT: "Cognitive unbinding" refers to the impaired synthesis of specialized cognitive activities in the brain and has been proposed as a mechanistic paradigm of unconsciousness. This article draws on recent neuroscientific data to revisit the tenets and predictions of cognitive unbinding, using general anesthesia as a representative state of unconsciousness. Current evidence from neuroimaging and neurophysiology supports the proposition that cognitive unbinding is a parsimonious explanation for the direct mechanism (or "proximate cause") of anesthetic-induced unconsciousness across multiple drug classes. The relevance of cognitive unbinding to sleep, disorders of consciousness, and psychological processes is also explored. It is concluded that cognitive unbinding is a viable neuroscientific framework for unconscious processes across the fields of anesthesiology, sleep neurobiology, neurology and psychoanalysis.
    Neuroscience & Biobehavioral Reviews 09/2013; · 10.28 Impact Factor
  • Eduardo E Icaza, George A Mashour
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    ABSTRACT: The psychedelic experience has been reported since antiquity, but there is relatively little known about the underlying neural mechanisms. A recent neuroimaging study on psilocybin revealed a pattern of decreased cerebral blood flow and functional disconnections that is surprisingly similar to that caused by various anesthetics. In this article, the authors review historical examples of psychedelic experiences induced by general anesthetics and then contrast the mechanisms by which these two drug classes generate altered states of consciousness.
    Anesthesiology 09/2013; · 5.16 Impact Factor
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    ABSTRACT: General anesthesia induces unconsciousness along with functional changes in brain networks. Considering the essential role of hub structures for efficient information transmission, the authors hypothesized that anesthetics have an effect on the hub structure of functional brain networks. Graph theoretical network analysis was carried out to study the network properties of 21-channel electroencephalogram data from 10 human volunteers anesthetized on two occasions. The functional brain network was defined by Phase Lag Index, a coherence measure, for three states: wakefulness, loss of consciousness induced by the anesthetic propofol, and recovery of consciousness. The hub nodes were determined by the largest centralities. The correlation between the altered hub organization and the phase relationship between electroencephalographic channels was investigated. Topology rather than connection strength of functional networks correlated with states of consciousness. The average path length, clustering coefficient, and modularity significantly increased after administration of propofol, which disrupted long-range connections. In particular, the strength of hub nodes significantly decreased. The primary hub location shifted from the parietal to frontal region, in association with propofol-induced unconsciousness. The phase lead of frontal to parietal regions in the α frequency band (8-13 Hz) observed during wakefulness reversed direction after propofol and returned during recovery. Propofol reconfigures network hub structure in the brain and reverses the phase relationship between frontal and parietal regions. Changes in network topology are more closely associated with states of consciousness than connectivity and may be the primary mechanism for the observed loss of frontal to parietal feedback during general anesthesia.
    Anesthesiology 09/2013; · 5.16 Impact Factor

Publication Stats

1k Citations
651.40 Total Impact Points

Institutions

  • 2014
    • University of Kansas
      Lawrence, Kansas, United States
  • 2008–2014
    • University of Michigan
      • Department of Anesthesiology
      Ann Arbor, Michigan, United States
  • 2007–2014
    • Concordia University–Ann Arbor
      Ann Arbor, Michigan, United States
  • 2013
    • University of New Haven
      New Haven, Connecticut, United States
    • Pohang University of Science and Technology
      • Department of Physics
      Andong, North Gyeongsang, South Korea
    • University of Pennsylvania
      Philadelphia, Pennsylvania, United States
  • 2012
    • University of Oxford
      • Nuffield Division of Anaesthetics (NDA)
      Oxford, ENG, United Kingdom
  • 2011
    • Ulsan University Hospital
      Urusan, Ulsan, South Korea
    • Charles University in Prague
      • 1. lékařská fakulta
      Praha, Hlavni mesto Praha, Czech Republic
  • 2009–2011
    • Washington University in St. Louis
      • Department of Anesthesiology
      Saint Louis, MO, United States
  • 2004–2007
    • Harvard Medical School
      Boston, Massachusetts, United States
  • 2006
    • Partners HealthCare
      Boston, Massachusetts, United States
  • 2004–2006
    • Massachusetts General Hospital
      • Department of Neurosurgery
      Boston, Massachusetts, United States
  • 1998–2001
    • Georgetown University
      • Department of Neurosurgery (MedStar)
      Washington, D. C., DC, United States
  • 1999
    • National Institutes of Health
      • Laboratory of Experimental Gerontology (LEG)
      Bethesda, MD, United States