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Emery N Brown - One of the best experts on this subject based on the ideXlab platform.

  • developing a personalized closed loop controller of medically Induced Coma in a rodent model
    Journal of Neural Engineering, 2019
    Co-Authors: Yuxiao Yang, Justin T Lee, Jennifer A Guidera, Ksenia Y Vlasov, Junzhu Pei, Emery N Brown
    Abstract:

    OBJECTIVE Personalized automatic control of medically-Induced Coma, a critical multi-day therapy in the intensive care unit, could greatly benefit clinical care and further provide a novel scientific tool for investigating how the brain response to anesthetic infusion rate changes during therapy. Personalized control would require real-time tracking of inter- and intra-subject variabilities in the brain response to anesthetic infusion rate while simultaneously delivering the therapy, which has not been achieved. Current control systems for medically-Induced Coma require a separate offline model fitting experiment to deal with inter-subject variabilities, which would lead to therapy interruption. Removing the need for these offline interruptions could help facilitate clinical feasbility. In addition, current systems do not track intra-subject variabilities. Tracking intra-subject variabilities is essential for studying whether or how the brain response to anesthetic infusion rate changes during therapy. Further, such tracking could enhance control precison and thus help facilitate clinical feasibility. APPROACH Here we develop a personalized closed-loop anesthetic delivery (CLAD) system in a rodent model that tracks both inter- and intra-subject variabilities in real time while simultaneously controlling the anesthetic in closed loop. We tested the CLAD in rats by administrating propofol to control the electroencephalogram (EEG) burst suppression. We first examined whether the CLAD can remove the need for offline model fitting interruption. We then used the CLAD as a tool to study whether and how the brain response to anesthetic infusion rate changes as a function of changes in the depth of medically-Induced Coma. Finally, we studied whether the CLAD can enhance control compared with prior systems by tracking intra-subject variabilities. MAIN RESULTS The CLAD precisely controlled the EEG burst suppression in each rat without performing offline model fitting experiments. Further, using the CLAD, we discovered that the brain response to anesthetic infusion rate varied during control, and that these variations correlated with the depth of medically-Induced Coma in a consistent manner across individual rats. Finally, tracking these variations reduced control bias and error by more than 70% compared with prior systems. SIGNIFICANCE This personalized CLAD provides a new tool to study the dynamics of brain response to anesthetic infusion rate and has significant implications for enabling clinically-feasible automatic control of medically-Induced Coma.

  • Variability in pharmacologically-Induced Coma for treatment of refractory status epilepticus
    PloS one, 2018
    Co-Authors: Durga Jonnalagadda, Emery N Brown, Patrick L. Purdon, Valdery Moura, M. Brandon Westover
    Abstract:

    Objective To characterize the amount of EEG suppression achieved in refractory status epilepticus (RSE) patients treated with pharmacologically-Induced Coma (PIC). Methods We analyzed EEG recordings from 35 RSE patients between 21–84 years-old who received PIC that target burst suppression and quantified the amount of EEG suppression using the burst suppression probability (BSP). Then we measured the variability of BSPs with respect to a reference level of BSP 0.8 ± 0.15. Finally, we also measured the variability of BSPs with respect to the amount of intravenous anesthetic drugs (IVADs) received by the patients. Results Patients remained in the reference BSP range for only 8% (median, interquartile range IQR [0, 29] %) of the total time under treatment. The median time with BSP below the reference range was 84% (IQR [37, 100] %). BSPs in some patients drifted significantly over time despite constant infusion rates of IVADs. Similar weight-normalized infusion rates of IVADs in different patients nearly always resulted in distinct BSPs (probability 0.93 (IQR [0.82, 1.0]). Conclusion This study quantitatively identified high variability in the amount of EEG suppression achieved in clinical practice when treating RSE patients. While some of this variability may arise from clinicians purposefully deviating from clinical practice guidelines, our results show that the high variability also arises in part from significant inter- and intra- individual pharmacokinetic/pharmacodynamic variation. Our results indicate that the delicate balance between maintaining sufficient EEG suppression in RSE patients and minimizing IVAD exposure in clinical practice is challenging to achieve. This may affect patient outcomes and confound studies seeking to determine an optimal amount of EEG suppression for treatment of RSE. Therefore, our analysis points to the need for developing an alternative paradigm, such as vigilant anesthetic management as happens in operating rooms, or closed-loop anesthesia delivery, for investigating and providing Induced-Coma therapy to RSE patients.

  • design implementation and evaluation of a physiological closed loop control device for medically Induced Coma
    International Conference of the IEEE Engineering in Medicine and Biology Society, 2017
    Co-Authors: Patrick L. Purdon, Emery N Brown, Ken Solt, Nathaniel M Sims, Brandon M Westover
    Abstract:

    Concerns regarding reliability and safety, as well as uncertainties about what constitutes adequate performance evaluation, have impeded the clinical translation of PCLC devices. We describe an attempt to address these challenges through design, implementation, and evaluation of a PCLC device for delivering medically-Induced Coma, with the intention to eventually conduct a clinical trial. This device works by automatically adjusting the infusion rate of propofol - a general anesthetic - in response to an electroencephalogram (EEG) pattern called burst suppression. We also designed and implemented a computational patient model which interfaces with hardware and produces realistic EEG signals in response to propofol infusion. The computational patient model is used in hardware-in-the-loop studies to evaluate the behavior of our PCLC device under realistic perturbations. Finally, we have tested the performance of our PCLC device in rodents. Results from these studies suggest that closed-loop control of medically-Induced Coma in humans is feasible and robust. Consequently, our work produced a PCLC device and relevant pre-clinical evidence in support of a pilot clinical trial.

  • EMBC - Design, implementation, and evaluation of a physiological closed-loop control device for medically-Induced Coma
    Annual International Conference of the IEEE Engineering in Medicine and Biology Society. IEEE Engineering in Medicine and Biology Society. Annual Inte, 2017
    Co-Authors: Patrick L. Purdon, Emery N Brown, Ken Solt, Nathaniel M Sims, M. Brandon Westover
    Abstract:

    Concerns regarding reliability and safety, as well as uncertainties about what constitutes adequate performance evaluation, have impeded the clinical translation of PCLC devices. We describe an attempt to address these challenges through design, implementation, and evaluation of a PCLC device for delivering medically-Induced Coma, with the intention to eventually conduct a clinical trial. This device works by automatically adjusting the infusion rate of propofol - a general anesthetic - in response to an electroencephalogram (EEG) pattern called burst suppression. We also designed and implemented a computational patient model which interfaces with hardware and produces realistic EEG signals in response to propofol infusion. The computational patient model is used in hardware-in-the-loop studies to evaluate the behavior of our PCLC device under realistic perturbations. Finally, we have tested the performance of our PCLC device in rodents. Results from these studies suggest that closed-loop control of medically-Induced Coma in humans is feasible and robust. Consequently, our work produced a PCLC device and relevant pre-clinical evidence in support of a pilot clinical trial.

  • spatial variation in automated burst suppression detection in pharmacologically Induced Coma
    International Conference of the IEEE Engineering in Medicine and Biology Society, 2015
    Co-Authors: Durga Jonnalagadda, Emery N Brown, Patrick L. Purdon, Valdery Moura, Brandon M Westover
    Abstract:

    Burst suppression is actively studied as a control signal to guide anesthetic dosing in patients undergoing medically Induced Coma. The ability to automatically identify periods of EEG suppression and compactly summarize the depth of Coma using the burst suppression probability (BSP) is crucial to effective and safe monitoring and control of medical Coma. Current literature however does not explicitly account for the potential variation in burst suppression parameters across different scalp locations. In this study we analyzed standard 19-channel EEG recordings from 8 patients with refractory status epilepticus who underwent pharmacologically Induced burst suppression as medical treatment for refractory seizures. We found that although burst suppression is generally considered a global phenomenon, BSP obtained using a previously validated algorithm varies systematically across different channels. A global representation of information from individual channels is proposed that takes into account the burst suppression characteristics recorded at multiple electrodes. BSP computed from this representative burst suppression pattern may be more resilient to noise and a better representation of the brain state of patients. Multichannel data integration may enhance the reliability of estimates of the depth of medical Coma.

T. C. A. M. Van Woerkom - One of the best experts on this subject based on the ideXlab platform.

Henk B.c. Verbiest - One of the best experts on this subject based on the ideXlab platform.

Jean A. Schumaker - One of the best experts on this subject based on the ideXlab platform.

  • Treatment of Refractory Status Epilepticus with Vagus Nerve Stimulator in an Elderly Patient
    World neurosurgery, 2016
    Co-Authors: Joseph S. Yazdi, Jean A. Schumaker
    Abstract:

    Background One of the risks of a traumatically Induced intracranial bleed is development of new onset seizures. Rarely would these seizures progress to status epilepticus (SE) or refractory SE. There is a lack of literature on the use of a vagus nerve stimulator in these situations in older adults. Case Description We present a 67-year-old patient who developed refractory status epilepticus within days after evacuation of a right-sided spontaneous subdural hematoma. He was refractory to multiple antiepileptic agents and phenobarbiturate- and propofol-Induced Coma. He then underwent a left vagus nerve stimulator (VNS) implantation. Within a few days of implantation, he improved dramatically. Within 2 weeks of VNS implantation, he was neurologically intact and was transferred to an inpatient rehabilitation facility. Within a short time thereafter, he was fully functional and able to take care of all of his activities. Conclusions A vagus nerve stimulator should be considered in cases of refractory status epilepticus, regardless of age. Excellent outcome can be achieved even if a short course of medication-Induced Coma is unsuccessful.

Shinung Ching - One of the best experts on this subject based on the ideXlab platform.

  • Real-time closed-loop control in a rodent model of medically Induced Coma using burst suppression.
    Anesthesiology, 2013
    Co-Authors: Shinung Ching, Jessica J. Chemali, Patrick L. Purdon, M. Brandon Westover, Max Y. Liberman, Jonathan D. Kenny, Ken Solt, Emery N Brown
    Abstract:

    Background A medically-Induced Coma is an anesthetic state of profound brain inactivation created to treat status epilepticus and to provide cerebral protection following traumatic brain injuries. We hypothesized that a closed-loop anesthetic delivery system could automatically and precisely control the electroencephalogram state of burst suppression and efficiently maintain a medically-Induced Coma.

  • a closed loop anesthetic delivery system for real time control of burst suppression
    Journal of Neural Engineering, 2013
    Co-Authors: Max Y. Liberman, Emery N Brown, Jessica J. Chemali, Shinung Ching
    Abstract:

    Objective. There is growing interest in using closed-loop anesthetic delivery (CLAD) systems to automate control of brain states (sedation, unconsciousness and antinociception) in patients receiving anesthesia care. The accuracy and reliability of these systems can be improved by using as control signals electroencephalogram (EEG) markers for which the neurophysiological links to the anesthetic-Induced brain states are well established. Burst suppression, in which bursts of electrical activity alternate with periods of quiescence or suppression, is a well-known, readily discernible EEG marker of profound brain inactivation and unconsciousness. This pattern is commonly maintained when anesthetics are administered to produce a medically-Induced Coma for cerebral protection in patients suffering from brain injuries or to arrest brain activity in patients having uncontrollable seizures. Although the Coma may be required for several hours or days, drug infusion rates are managed inefficiently by manual adjustment. Our objective is to design a CLAD system for burst suppression control to automate management of medically-Induced Coma. Approach. We establish a CLAD system to control burst suppression consisting of: a two-dimensional linear system model relating the anesthetic brain level to the EEG dynamics; a new control signal, the burst suppression probability (BSP) defining the instantaneous probability of suppression; the BSP filter, a state-space algorithm to estimate the BSP from EEG recordings; a proportional–integral controller; and a system identification procedure to estimate the model and controller parameters. Main results. We demonstrate reliable performance of our system in simulation studies of burst suppression control using both propofol and etomidate in rodent experiments based on Vijn and Sneyd, and in human experiments based on the Schnider pharmacokinetic model for propofol. Using propofol, we further demonstrate that our control system reliably tracks changing target levels of burst suppression in simulated human subjects across different epidemiological profiles. Significance. Our results give new insights into CLAD system design and suggest a control-theory framework to automate second-to-second control of burst suppression for management of medically-Induced Coma.