Eric T Pierce

Massachusetts General Hospital, Boston, Massachusetts, United States

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Publications (13)50.76 Total impact

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    ABSTRACT: Electroencephalogram patterns observed during sedation with dexmedetomidine appear similar to those observed during general anesthesia with propofol. This is evident with the occurrence of slow (0.1 to 1 Hz), delta (1 to 4 Hz), propofol-induced alpha (8 to 12 Hz), and dexmedetomidine-induced spindle (12 to 16 Hz) oscillations. However, these drugs have different molecular mechanisms and behavioral properties and are likely accompanied by distinguishing neural circuit dynamics.
    Anesthesiology 09/2014; · 5.16 Impact Factor
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    ABSTRACT: (Background) Accurate quantitative analysis of the changes in responses to external stimuli is crucial for characterizing the timing of loss and recovery of consciousness induced by anesthetic drugs. We studied induction and emergence from unconsciousness achieved by administering a computer-controlled infusion of propofol to ten human volunteers. We evaluated loss and recovery of consciousness by having subjects execute every four seconds two interleaved computer delivered behavioral tasks: responding to verbal stimuli (neutral words or the subject's name), or less salient stimuli of auditory clicks. (New Method) We analyzed the data using state-space methods. For each stimulus type the observation model is a two-stage binomial model and the state model is two dimensional random walk in which one cognitive state governs the probability of responding and the second governs the probability of correctly responding given a response. We fit the model to the experimental data using Bayesian Monte Carlo methods. (Results) During induction subjects lost responsiveness to less salient clicks before losing responsiveness to the more salient verbal stimuli. During emergence subjects regained responsiveness to the more salient verbal stimuli before regaining responsiveness to the less salient clicks. (Comparison with Existing Method(s)) The current state-space model is an extension of previous model used to analyze learning and behavioral performance. In this study, the probability of responding on each trial is obtained separately from the probability of behavioral performance. (Conclusions) Our analysis provides a principled quantitative approach for defining loss and recovery of consciousness in experimental studies of general anesthesia.
    Journal of neuroscience methods 04/2014; · 2.30 Impact Factor
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    ABSTRACT: Rhythmic oscillations shape cortical dynamics during active behavior, sleep, and general anesthesia. Cross-frequency phase-amplitude coupling is a prominent feature of cortical oscillations, but its role in organizing conscious and unconscious brain states is poorly understood. Using high-density EEG and intracranial electrocorticography during gradual induction of propofol general anesthesia in humans, we discovered a rapid drug-induced transition between distinct states with opposite phase-amplitude coupling and different cortical source distributions. One state occurs during unconsciousness and may be similar to sleep slow oscillations. A second state occurs at the loss or recovery of consciousness and resembles an enhanced slow cortical potential. These results provide objective electrophysiological landmarks of distinct unconscious brain states, and could be used to help improve EEG-based monitoring for general anesthesia.
    Journal of Neuroscience 01/2014; 34(3):839-45. · 6.91 Impact Factor
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    ABSTRACT: Unconsciousness is a fundamental component of general anesthesia (GA), but anesthesiologists have no reliable ways to be certain that a patient is unconscious. To develop EEG signatures that track loss and recovery of consciousness under GA, we recorded high-density EEGs in humans during gradual induction of and emergence from unconsciousness with propofol. The subjects executed an auditory task at 4-s intervals consisting of interleaved verbal and click stimuli to identify loss and recovery of consciousness. During induction, subjects lost responsiveness to the less salient clicks before losing responsiveness to the more salient verbal stimuli; during emergence they recovered responsiveness to the verbal stimuli before recovering responsiveness to the clicks. The median frequency and bandwidth of the frontal EEG power tracked the probability of response to the verbal stimuli during the transitions in consciousness. Loss of consciousness was marked simultaneously by an increase in low-frequency EEG power (<1 Hz), the loss of spatially coherent occipital alpha oscillations (8-12 Hz), and the appearance of spatially coherent frontal alpha oscillations. These dynamics reversed with recovery of consciousness. The low-frequency phase modulated alpha amplitude in two distinct patterns. During profound unconsciousness, alpha amplitudes were maximal at low-frequency peaks, whereas during the transition into and out of unconsciousness, alpha amplitudes were maximal at low-frequency nadirs. This latter phase-amplitude relationship predicted recovery of consciousness. Our results provide insights into the mechanisms of propofol-induced unconsciousness, establish EEG signatures of this brain state that track transitions in consciousness precisely, and suggest strategies for monitoring the brain activity of patients receiving GA.
    Proceedings of the National Academy of Sciences 03/2013; · 9.81 Impact Factor
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    ABSTRACT: Gravity-driven micro-drip infusion sets allow control of medication dose delivery by adjusting drops per minute. When the roller clamp is fully open, flow in the drip chamber can be a continuous fluid column rather than discrete, countable, drops. We hypothesized that during this "wide-open" state, drug delivery becomes dependent on factors extrinsic to the micro-drip set and is therefore difficult to predict. We conducted laboratory experiments to characterize volume delivery under various clinically relevant conditions of wide-open flow in an in vitro laboratory model. A micro-drip infusion set, plugged into a bag of normal saline, was connected to a high-flow stopcock at the distal end. Vertically oriented IV catheters (gauges 14-22) were connected to the stopcock. The fluid meniscus height in the bag was fixed (60-120 cm) above the outflow point. The roller clamp on the infusion set was in fully open position for all experiments resulting in a continuous column of fluid in the drip chamber. Fluid volume delivered in 1 minute was measured 4 times with each condition. To model resistive effects of carrier flow, volumetric infusion pumps were used to deliver various flow rates of normal saline through a carrier IV set into which a micro-drip infusion was "piggybacked." We also compared delivery by micro-drip infusion sets from 3 manufacturers. The volume of fluid delivered by gravity-driven infusion under wide-open conditions (continuous fluid column in drip chamber) varied 2.9-fold (95% confidence interval, 2.84-2.96) depending on catheter size and fluid column height. Total model resistance of the micro-drip with stopcock and catheter varied with flow rate. Volume delivered by the piggybacked micro-drip decreased up to 29.7% ± 0.8% (mean ± SE) as the carrier flow increased from 0 to 1998 mL/min. Delivery characteristics of the micro-drip infusion sets from 3 different manufacturers were similar. Laboratory simulation of clinical situations with gravity-driven micro-drip infusion sets under wide-open flow conditions revealed that infusion rate (drug and/or volume delivery) can vary widely depending on extrinsic factors including catheter size, fluid column height, and carrier flow. The variable resistance implies nonlaminar flow in the micro-drip model that cannot be easily predicted mathematically. These findings support the use of mechanical pumps instead of gravity-driven micro-drips to enhance the precision and safety of IV infusions, especially for vasoactive drugs.
    Anesthesia and analgesia 03/2013; 116(3):614-8. · 3.08 Impact Factor
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    ABSTRACT: Accurate quantification of loss of response to external stimuli is essential for understanding the mechanisms of loss of consciousness under general anesthesia. We present a new approach for quantifying three possible outcomes that are encountered in behavioral experiments during general anesthesia: correct responses, incorrect responses and no response. We use a state-space model with two state variables representing a probability of response and a conditional probability of correct response. We show applications of this approach to an example of responses to auditory stimuli at varying levels of propofol anesthesia ranging from light sedation to deep anesthesia in human subjects. The posterior probability densities of model parameters and the response probability are computed within a Bayesian framework using Markov Chain Monte Carlo methods.
    Conference proceedings: ... Annual International Conference of the IEEE Engineering in Medicine and Biology Society. IEEE Engineering in Medicine and Biology Society. Conference 08/2011; 2011:4705-8.
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    ABSTRACT: Time and frequency domain analyses of scalp EEG recordings are widely used to track changes in brain states under general anesthesia. Although these analyses have suggested that different spatial patterns are associated with changes in the state of general anesthesia, the extent to which these patterns are spatially coordinated has not been systematically characterized. Global coherence, the ratio of the largest eigenvalue to the sum of the eigenvalues of the cross-spectral matrix at a given frequency and time, has been used to analyze the spatiotemporal dynamics of multivariate time-series. Using 64-lead EEG recorded from human subjects receiving computer-controlled infusions of the anesthetic propofol, we used surface Laplacian referencing combined with spectral and global coherence analyses to track the spatiotemporal dynamics of the brain's anesthetic state. During unconsciousness the spectrograms in the frontal leads showed increasing α (8-12 Hz) and δ power (0-4 Hz) and in the occipital leads δ power greater than α power. The global coherence detected strong coordinated α activity in the occipital leads in the awake state that shifted to the frontal leads during unconsciousness. It revealed a lack of coordinated δ activity during both the awake and unconscious states. Although strong frontal power during general anesthesia-induced unconsciousness--termed anteriorization--is well known, its possible association with strong α range global coherence suggests highly coordinated spatial activity. Our findings suggest that combined spectral and global coherence analyses may offer a new approach to tracking brain states under general anesthesia.
    Proceedings of the National Academy of Sciences 05/2011; 108(21):8832-7. · 9.81 Impact Factor
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    ABSTRACT: Efforts to assure high-quality, safe, clinical care depend upon capturing information about near-miss and adverse outcome events. Inconsistent or unreliable information capture, especially for infrequent events, compromises attempts to analyze events in quantitative terms, understand their implications, and assess corrective efforts. To enhance reporting, we developed a secure, electronic, mandatory system for reporting quality assurance data linked to our electronic anesthesia record. We used the capabilities of our anesthesia information management system (AIMS) in conjunction with internally developed, secure, intranet-based, Web application software. The application is implemented with a backend allowing robust data storage, retrieval, data analysis, and reporting capabilities. We customized a feature within the AIMS software to create a hard stop in the documentation workflow before the end of anesthesia care time stamp for every case. The software forces the anesthesia provider to access the separate quality assurance data collection program, which provides a checklist for targeted clinical events and a free text option. After completing the event collection program, the software automatically returns the clinician to the AIMS to finalize the anesthesia record. The number of events captured by the departmental quality assurance office increased by 92% (95% confidence interval [CI] 60.4%-130%) after system implementation. The major contributor to this increase was the new electronic system. This increase has been sustained over the initial 12 full months after implementation. Under our reporting criteria, the overall rate of clinical events reported by any method was 471 events out of 55,382 cases or 0.85% (95% CI 0.78% to 0.93%). The new system collected 67% of these events (95% confidence interval 63%-71%). We demonstrate the implementation in an academic anesthesia department of a secure clinical event reporting system linked to an AIMS. The system enforces entry of quality assurance information (either no clinical event or notification of a clinical event). System implementation resulted in capturing nearly twice the number of events at a relatively steady case load.
    Anesthesia and analgesia 03/2011; 112(5):1218-25. · 3.08 Impact Factor
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    ABSTRACT: Coherence analysis characterizes frequency-dependent covariance between signals, and is useful for multivariate oscillatory data often encountered in neuroscience. The global coherence provides a summary of coherent behavior in high-dimensional multivariate data by quantifying the concentration of variance in the first mode of an eigenvalue decomposition of the cross-spectral matrix. Practical application of this useful method is sensitive to noise, and can confound coherent activity in disparate neural populations or spatial locations that have a similar frequency structure. In this paper we describe two methodological enhancements to the global coherence procedure that increase robustness of the technique to noise, and that allow characterization of how power within specific coherent modes change through time.
    Conference proceedings: ... Annual International Conference of the IEEE Engineering in Medicine and Biology Society. IEEE Engineering in Medicine and Biology Society. Conference 01/2011; 2011:4725-8.
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    ABSTRACT: In this article, we present a point process method to assess dynamic baroreflex sensitivity (BRS) by estimating the baroreflex gain as focal component of a simplified closed-loop model of the cardiovascular system. Specifically, an inverse Gaussian probability distribution is used to model the heartbeat interval, whereas the instantaneous mean is identified by linear and bilinear bivariate regressions on both the previous R-R intervals (RR) and blood pressure (BP) beat-to-beat measures. The instantaneous baroreflex gain is estimated as the feedback branch of the loop with a point-process filter, while the RR-->BP feedforward transfer function representing heart contractility and vasculature effects is simultaneously estimated by a recursive least-squares filter. These two closed-loop gains provide a direct assessment of baroreflex control of heart rate (HR). In addition, the dynamic coherence, cross bispectrum, and their power ratio can also be estimated. All statistical indices provide a valuable quantitative assessment of the interaction between heartbeat dynamics and hemodynamics. To illustrate the application, we have applied the proposed point process model to experimental recordings from 11 healthy subjects in order to monitor cardiovascular regulation under propofol anesthesia. We present quantitative results during transient periods, as well as statistical analyses on steady-state epochs before and after propofol administration. Our findings validate the ability of the algorithm to provide a reliable and fast-tracking assessment of BRS, and show a clear overall reduction in baroreflex gain from the baseline period to the start of propofol anesthesia, confirming that instantaneous evaluation of arterial baroreflex control of HR may yield important implications in clinical practice, particularly during anesthesia and in postoperative care.
    Annals of Biomedical Engineering 10/2010; 39(1):260-76. · 3.23 Impact Factor
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    ABSTRACT: It has been long appreciated that anesthetic drugs induce stereotyped changes in electroencephalogram (EEG), but the relationships between the EEG and underlying brain function remain poorly understood. Functional imaging methods including positron emission tomography (PET) and functional magnetic resonance imaging (fMRI), have become important tools for studying how anesthetic drugs act in the human brain to induce the state of general anesthesia. To date, no investigation has combined functional MRI with EEG to study general anesthesia. We report here a paradigm for conducting combined fMRI and EEG studies of human subjects under general anesthesia. We discuss the several technical and safety problems that must be solved to undertake this type of multimodal functional imaging and show combined recordings from a human subject. Combined fMRI and EEG exploits simultaneously the high spatial resolution of fMRI and the high temporal resolution of EEG. In addition, combined fMRI and EEG offers a direct way to relate established EEG patterns induced by general anesthesia to changes in neural activity in specific brain regions as measured by changes in fMRI blood oxygen level dependent (BOLD) signals.
    Annals of the New York Academy of Sciences 04/2009; 1157:61-70. · 4.38 Impact Factor
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    BMC Neuroscience 01/2009; · 3.00 Impact Factor
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    ABSTRACT: Quantitative evaluation of respiratory sinus arrhythmia (RSA) may provide important information in clinical practice of anesthesia and postoperative care. In this paper, we apply a point process method to assess dynamic RSA during propofol general anesthesia. Specifically, an inverse Gaussian probability distribution is used to model the heartbeat interval, whereas the instantaneous mean is identified by a linear or bilinear bivariate regression on the previous R-R intervals and respiratory measures. The estimated second-order bilinear interaction allows us to evaluate the nonlinear component of the RSA. The instantaneous RSA gain and phase can be estimated with an adaptive point process filter. The algorithm's ability to track non-stationary dynamics is demonstrated using one clinical recording. Our proposed statistical indices provide a valuable quantitative assessment of instantaneous cardiorespiratory control and heart rate variability (HRV) during general anesthesia.
    Conference proceedings: ... Annual International Conference of the IEEE Engineering in Medicine and Biology Society. IEEE Engineering in Medicine and Biology Society. Conference 01/2009; 2009:5336-9.