Effect of Ketamine on the Bispectral Index, Spectral Edge Frequency, and Surgical Pleth Index During Propofol-Remifentanil Anesthesia: An Observational Prospective Trial

Background: Ketamine administration during stable propofol anesthesia is known to be associated with an increase in bispectral index (BIS) but a "deepening" in the level of hypnosis. This study aimed to evaluate the association between the effect-site concentration of ketamine (CeK) and 2 electroencephalogram (EEG)-derived parameters, the BIS and spectral edge frequency (SEF95), after the administration of a ketamine bolus. Secondary aims included investigating the BIS and SEF95 variations with time and changes in the surgical pleth index (SPI). Methods: We conducted an observational, prospective, single-center study analyzing intraoperative data from 14 adult female patients undergoing breast oncologic surgery. During stable propofol-remifentanil target-controlled infusion (TCI) anesthesia, a ketamine analgesic bolus was delivered with the target CeK set to 1 μg.mL-1 (Domino model) corresponding to a dose of 0.57 mg.kg-1 (interquartile range [IQR] 0.56-0.57 mg.kg-1). Once the CeK reached a value of 1 μg.mL-1, the target CeK was set to 0 μg.mL-1. We determined the median BIS, SEF95, and SPI trends with time and as a function of the modeled CeK. Results: BIS and SEF95 showed no significant change from when ketamine was administered to when CeK=1 μg.mL-1, but a significant increase was observed at lower CeKs. The maximum BIS was reached at 16.0 minutes [10.2-22.7 minutes] after CeK=1 μg.mL-1, at CeK=0.22 μg.mL-1 [0.12-0.41 μg.mL-1]. The peak SEF95 value was observed at 10.0 minutes [8.62-14.1 minutes] after CeK=1 μg.mL-1, at CeK=0.43 μg.mL-1 [0.25-0.50 μg.mL-1]. No significant association was found between CeK and the registered SPI values. Conclusions: Our results show that BIS and SEF95, but not SPI, follow a CeK-dependent trend after administering a ketamine bolus. Interestingly, their peak values were not reached at CeK=1 μg.mL-1, but after several minutes after the drug infusion at CeKs in the 0.2 to 0.5 μg.mL-1 range. This may be explained by the specific pharmacodynamics of ketamine and its varying effects at different concentrations, as well as by the time delay associated with the calculation of the BIS.