The effect of ketamine on depth of hypnosis indices during total intravenous anesthesia—a comparative study using a novel electroencephalography case replay system

Ketamine may affect the reliability of electroencephalographic (EEG) depth-of-hypnosis indices as it affects power in high-frequency EEG components. The purpose of this study was to compare the effects of ketamine on three commonly-used depth-of-hypnosis indices by extending our EEG simulator to allow replay of previously-recorded EEG. Secondary analysis of previously-collected data from a randomized controlled trial of intravenous anesthesia with ketamine: Group 0.5 [ketamine, 0.5 mg kg⁻¹ bolus followed by a 10 mcg kg⁻¹ min⁻¹ infusion], Group 0.25 [ketamine, 0.25 mg kg⁻¹ bolus, 5 mcg kg⁻¹ min⁻¹ infusion], and Control [no ketamine]. EEG data were replayed to three monitors: NeuroSENSE (WAV), Bispectral Index (BIS), and Entropy (SE). Differences in depth-of-hypnosis indices during the initial 15 min after induction of anesthesia were compared between monitors, and between groups. Monitor agreement was evaluated using Bland–Altman analysis. Available data included 45.6 h of EEG recordings from 27 cases. Ketamine was associated with higher depth-of-hypnosis index values measured at 10 min (BIS, χ² = 8.01, p = 0.018; SE, χ² = 11.44, p = 0.003; WAV, χ² = 9.19, p = 0.010), and a higher proportion of index values > 60 for both ketamine groups compared to the control group. Significant differences between monitors were not observed, except between BIS and SE in the control group. Ketamine did not change agreement between monitors. The ketamine-induced increase in depth-of-hypnosis indices was observed consistently across the three EEG monitoring algorithms evaluated. The observed increase was likely caused by a power increase in the beta and gamma bands. However, there were no lasting differences in depth-of-hypnosis reported between the three compared indices.