Background. The gold standard anesthesia for deep brain stimulation (DBS) surgery is the "awake" approach, using local anesthesia alone. While it offers high-quality microelectrode recordings and clinical assessment of the stimulation therapeutic window, it potentially causes patients extreme stress and might result in suboptimal surgical outcomes. However, the alternative of general anesthesia or deep sedation dramatically reduces reliability of physiological navigation and therapeutic window assessment, thus potentially diminishing the accuracy of lead localization. We therefore designed a prospective double-blinded randomized controlled trial to investigate a novel anesthesia regimen of ketamine-induced conscious sedation for DBS surgery. Methods. Patients with Parkinson's disease undergoing subthalamic nucleus DBS surgery were enrolled. Patients were randomly assigned to either the experimental or control group. During the physiological navigation phase, the experimental group received ketamine infusion at a dosage of 0.25 mg/kg/hr, while the control group received normal saline. Both groups received moderate propofol sedation before and after the physiological navigation phase. Primary outcomes were non-inferiority of electrophysiological quality, including multiunit recordings, EEG, EMG, bispectral index and lead localization accuracy according to postoperative CT scans. Secondary outcomes included patients' satisfaction level measured using Iowa satisfaction with anesthesia scale for awake procedures. Potential side effects and adverse events were also monitored, including hemodynamics (blood pressure, heart rate) and cognition (hallucinations during surgery and early post-operative cognition using Montreal Cognitive Assessment). Results. Thirty patients, 15 from each group, were included in the study and analysed. Intra-operatively, the electrophysiological signature of the subthalamic nucleus was similar under ketamine and saline. Tremor amplitude was slightly lower under ketamine (p = 0.002). The accuracy of lead position was comparable in both groups. Postoperatively, patients in the ketamine group reported significantly higher satisfaction with anesthesia. The improvement in Unified Parkinson's disease rating scale part-III was similar between the groups. No negative effects of ketamine on hemodynamic stability or cognition were reported perioperatively. Additionally, no procedure-related complications were reported in either group, besides one case of peri-lead edema in the control group. Conclusion. This study demonstrates that ketamine induced conscious sedation during physiological navigation in DBS surgery resulted in non-inferior intra-operative, post-surgical and patient satisfaction outcomes compared to the commonly used standard awake protocol, without major disadvantages. Future studies should investigate the applicability of this protocol in other awake neurosurgical procedures, such as DBS for other targets and indications, and awake craniotomy for tumor resection and epilepsy.

The authors have declared no competing interest.

NCT04716296

This study was funded by Silberstein foundation, ISF Breakthrough grant (#1738/22), the Collaborative Research center TRR295, Germany (#3380/20) and grant of the Israeli Science Foundation (ISF)

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Ethics committee/IRB 328/50 of Rabin Medical Center, Beilinson Hospital, Israel gave ethical approval for this work

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