Real-time closed-loop control in a rodent model of medically induced coma using burst suppression

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 closedloop 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.