Fig. 4. (A ) The effect of escalating bolus doses of carboetomidate on the burst suppression ratio in a rat. The carboetomidate doses represent one, two, and four times the ED⁵⁰for loss of righting reflexes in rats. Each bolus was given over 6 s, and the burst suppression ratio was calculated from the time-differentiated electroencephalogram. (B ) Mean burst suppression ratio during each 6 s epoch recorded from five rats on administration of a carboetomidate bolus (10 mg/kg), followed by a 15 min closed-loop infusion with the target burst suppression ratio of 40%. The curve is an exponential fit of the postinfusion data. Inset1: Representative baseline raw electroencephalogram obtained from an individual rat before the administration of carboetomidate.2Corresponding baseline time-differentiated electroencephalogram before the administration of carboetomidate.3Representative raw electroencephalogram obtained from the same rat during closed-loop infusion of carboetomidate.4Corresponding time-differentiated electroencephalogram during the carboetomidate infusion. Each data point represents the burst suppression ratio during a 6 s epoch. All measurements were performed in the presence of inhaled isoflurane, 1%.