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.