Effect of ketamine on the NeuroSENSE WAV CNS during propofol anesthesia; a randomized feasibility trial.

Dose-dependent effects of ketamine on processed electroencephalographic depth-of-hypnosis indices have been reported. Limited data are available for the NeuroSENSE WAV _CNS index. Our aim was to establish the feasibility of closed-loop propofol-remifentanil anesthesia guided by the WAV _CNS index in the presence of an analgesic dose of ketamine. Thirty ASA I-II adults, 18-54 years, requiring general anesthesia for anterior cruciate ligament surgery were randomized to receive: full-dose [ketamine, 0.5 mg kg ^-1 initial bolus, 10 mcg kg ^-1 min ^-1 infusion] (recommended dose for postoperative pain management); half-dose [ketamine, 0.25 mg kg ^-1 bolus, 5 mcg kg ^-1 min ^-1 infusion]; or control [no ketamine]. After the ketamine bolus, patients received 1.0 mcg kg ^-1 remifentanil over 30 s, then 1.5 mg kg ^-1 propofol over 30 s, followed by manually-adjusted propofol-remifentanil anesthesia. The WAV _CNS was > 60 for 7/9 patients in the full-dose group at 7 min after starting the propofol infusion. This was inconsistent with clinical observations of depth-of-hypnosis and significantly higher than control (median difference [MD] 17.0, 95% confidence interval [CI] 11.4-26.8). WAV _CNS was median [interquartile range] 49.3 [42.2-62.6] in the half-dose group, and not different to control (MD 5.1, 95% CI - 4.9 to 17.9). During maintenance of anesthesia, the WAV _CNS was higher in the full-dose group compared to control (MD 14.7, 95% CI 10.2-19.2) and in the half-dose group compared to control (MD 11.4, 95% CI 4.7-20.4). The full-dose of ketamine recommended for postoperative pain management had a significant effect on the WAV _CNS . This effect should be considered when using the WAV _CNS to guide propofol-remifentanil dosing.Trial Registration ClinicalTrails.gov No. NCT02908945.