• ShiNung Ching, Max Y Liberman, Jessica J Chemali, M Brandon Westover, Jonathan D Kenny, Ken Solt, Patrick L Purdon, and Emery N Brown.
• * Research Fellow, Department of Anaesthesia, Harvard Medical School, Boston, Massachusetts; Research Fellow, Department of Anesthesia, Critical Care, and Pain Medicine, Massachusetts General Hospital, Boston, Massachusetts; Research Affiliate, Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, Massachusetts. † Research Assistant, Department of Anesthesia, Critical Care, and Pain Medicine, Massachusetts General Hospital. ‡ Instructor, Department of Neurology, Harvard Medical School; Assistant in Neurology, Department of Neurology, Massachusetts General Hospital. § Assistant Professor, Department of Anaesthesia, Harvard Medical School; Assistant Anesthetist, Department of Anesthesia, Critical Care, and Pain Medicine, Massachusetts General Hospital; Research Affiliate, Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology. ‖ Instructor, Department of Anaesthesia, Harvard Medical School; Instructor, Department of Anesthesia, Critical Care, and Pain Medicine, Massachusetts General Hospital; Research Affiliate, Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology. # Warren M. Zapol Professor of Anaesthesia, Department of Anaesthesia, Harvard Medical School; Anesthetist, Department of Anesthesia, Critical Care, and Pain Medicine, Massachusetts General Hospital; Professor of Computational Neuroscience, Edward Hood Taplin Professor of Medical Engineering, Institute for Medical Engineering and Sciences, Department of Brain and Cognitive Sciences, Harvard-MIT Health Sciences and Technology Program, Massachusetts Institute of Technology.
• Anesthesiology. 2013 Oct 1; 119 (4): 848860848-60.

BackgroundA medically induced coma is an anesthetic state of profound brain inactivation created to treat status epilepticus and to provide cerebral protection after traumatic brain injuries. The authors 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.MethodsIn six rats, the authors implemented a closed-loop anesthetic delivery system for propofol consisting of: a computer-controlled pump infusion, a two-compartment pharmacokinetics model defining propofol's electroencephalogram effects, the burst-suppression probability algorithm to compute in real time from the electroencephalogram the brain's burst-suppression state, an online parameter-estimation procedure and a proportional-integral controller. In the control experiment each rat was randomly assigned to one of the six burst-suppression probability target trajectories constructed by permuting the burst-suppression probability levels of 0.4, 0.65, and 0.9 with linear transitions between levels.ResultsIn each animal the controller maintained approximately 60 min of tight, real-time control of burst suppression by tracking each burst-suppression probability target level for 15 min and two between-level transitions for 5-10 min. The posterior probability that the closed-loop anesthetic delivery system was reliable across all levels was 0.94 (95% CI, 0.77-1.00; n = 18) and that the system was accurate across all levels was 1.00 (95% CI, 0.84-1.00; n = 18).ConclusionThe findings of this study establish the feasibility of using a closed-loop anesthetic delivery systems to achieve in real time reliable and accurate control of burst suppression in rodents and suggest a paradigm to precisely control medically induced coma in patients.

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