Real-time Closed-loop Control in a Rodent Model of Medically Induced Coma Using Burst Suppression
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Author(s)
Liberman, Max Y.
Chemali, Jessica J.
Westover, M. Brandon
Kenny, Jonathan D.
Solt, Ken
Purdon, Patrick Lee
Ching, Shinung
Brown, Emery Neal
Date Issued
October 2013
Journal
Anesthesiology
Publisher
Ovid Technologies (Wolters Kluwer) - Lippincott Williams & Wilkins
Citation
Ching, ShiNung, Max Y. Liberman, Jessica J. Chemali, M. Brandon Westover, Jonathan D. Kenny, Ken Solt, Patrick L. Purdon, and Emery N. Brown. “Real-Time Closed-Loop Control in a Rodent Model of Medically Induced Coma Using Burst Suppression.” Anesthesiology 119, no. 4 (October 2013): 848–860.
Version
Author's final manuscript
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).
Conclusion:: 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.
A closed-loop anesthesia delivery system using a computer-controlled infusion of propofol can achieve a reliable and accurate real-time control of burst suppression in rats.
MIT Department
Massachusetts Institute of Technology. Institute for Medical Engineering & Science
Harvard University--MIT Division of Health Sciences and Technology
Massachusetts Institute of Technology. Department of Brain and Cognitive Sciences
Picower Institute for Learning and Memory
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DOI of Published Version
https://doi.org/10.1097/ALN.0b013e31829d4ab4
