title: Real-time closed-loop control in a rodent model of medically induced coma using burst suppression.
abstract: BACKGROUND
  A 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.
  
  
  METHODS
  In 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.
  
  
  RESULTS
  In 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).
  
  
  CONCLUSIONS
  The 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.
authors.affiliation: * 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.
authors.forename: ShiNung
authors.initials: S
authors.lastname: Ching
authors.forename: Max Y
authors.initials: MY
authors.lastname: Liberman
authors.forename: Jessica J
authors.initials: JJ
authors.lastname: Chemali
authors.forename: M Brandon
authors.initials: MB
authors.lastname: Westover
authors.forename: Jonathan D
authors.initials: JD
authors.lastname: Kenny
authors.forename: Ken
authors.initials: K
authors.lastname: Solt
authors.forename: Patrick L
authors.initials: PL
authors.lastname: Purdon
authors.forename: Emery N
authors.initials: EN
authors.lastname: Brown
mesh_terms: D000771:Anesthesia, Intravenous / Q000295:instrumentation* / Q000379:methods; D018686:Anesthetics, Intravenous / Q000008:administration & dosage*; D000818:Animals; D001921:Brain / Q000187:drug effects*; D003128:Coma / Q000139:chemically induced*; D004195:Disease Models, Animal; D016503:Drug Delivery Systems; D004569:Electroencephalography / Q000187:drug effects* / Q000379:methods; D005240:Feasibility Studies; D007262:Infusions, Intravenous / Q000295:instrumentation / Q000379:methods; D008297:Male; D015742:Propofol / Q000008:administration & dosage*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015203:Reproducibility of Results
chemical_list: D018686:Anesthetics, Intravenous; D015742:Propofol