Deep Brain Stimulation, Esketamine, PD - Parkinson's Disease
Conditions
Brief summary
Under regional anesthesia, subthalamic nucleus deep brain stimulation (STN-DBS) has proven to be an effective therapeutic approach for improving motor symptoms in Parkinson's disease. However, a significant portion of Parkinson's disease (PD) patients is unable to cooperate with the surgery, necessitating the use of awake sedation. Nevertheless, the administration of anesthetic drugs often impacts the electrical signals recorded by microelectrodes to varying degrees. This study is designed as a prospective, randomized, placebo-controlled, double-blind, two-arm investigation. PD patients scheduled for bilateral STN-DBS surgery will be randomly assigned to either the Dexmedetomidine group or the Dexmedetomidine combined with Esketamine group. The differences in neural activity between the two groups will be assessed using the normalized root mean square (NRMS) method. The primary outcome measure is NRMS, while secondary outcome measures include differences in beta oscillation power spectrum analysis, postoperative delirium incidence, postoperative changes in sleep disturbances, postoperative depression, anxiety status, and occurrence of adverse events.
Detailed description
Regional anesthesia for subthalamic nucleus deep brain stimulation (STN-DBS) is an effective treatment method for improving motor symptoms in Parkinson's disease. However, the majority of Parkinson's disease (PD) patients require awake sedation during the procedure. Nevertheless, the administration of anesthetic drugs often impacts the microelectrode recording (MER) signals to varying degrees. Current research suggests that Esketamine can provide sedation and analgesia while preserving the active brain electrical signals of patients. Additionally, it has been shown to improve sleep disturbances and alleviate depression and anxiety in patients.This study aims to compare the impact of Dexmedetomidine alone and Dexmedetomidine combined with Esketamine on MER during awake sedation in PD patients undergoing STN-DBS surgery, to clarify the influence of Esketamine on the intraoperative electrical signals of PD patients under awake sedation during DBS surgery. The experiment is designed as a prospective, randomized, placebo-controlled, non-inferiority study with a double-blind, two-arm design. PD patients scheduled for bilateral STN-DBS surgery will be randomly assigned to either the Dexmedetomidine group or the Dexmedetomidine combined with Esketamine group. The differences in neural activity between the two groups will be assessed using the normalized root mean square (NRMS) method. The primary outcome measure is NRMS, while secondary outcome measures include differences in beta oscillation power spectrum analysis, postoperative delirium incidence, postoperative changes in sleep disturbances, postoperative depression, anxiety status, and occurrence of adverse events.
Interventions
DRUGesketamine
After the craniotomy, a continuous infusion of ketamine at a rate of 0.3 mg/kg/h (0.3 ml/kg/h) is administered until the completion of electrode implantation, prior to microelectrode recording (MER) and electrode insertion. After the administration of the drug, close monitoring of the patient's blood pressure and heart rate is conducted to maintain circulatory stability.
DRUGnormal Saline
After the craniotomy, a continuous infusion of normal saline at a rate of 0.3 ml/kg/h is administered until the completion of electrode implantation, prior to microelectrode recording (MER) and electrode insertion. After the administration of the drug, close monitoring of the patient's blood pressure and heart rate is conducted to maintain circulatory stability.
Sponsors
Beijing Tiantan Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
50 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
1.50-80 years old, ASA grade II-III; 2.Bilateral STN-DBS of patients with Parkinson's disease; 3.Signed informed consent.
Exclusion criteria
1. Obstructive sleep apnea; 2. BMI \> 30kg/m2; 3. Estimated difficult airway; 4. Severe preoperative anxiety; 5. Serious dysfunction of important organs (i.e. heart failure, renal or liver dysfunction) 6. A history of allergy to the anaesthetics.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| NRMS | 1 day (during MER recording) | The investigators will use the root mean square (RMS) value of the MER sampled signal as the main parameter for evaluating electrode position. RMS values change with the electrode properties and other external drives related to the operating room; therefore, it is crucial to normalize the RMS to comparable values. Thus, each session's RMS in a trajectory is divided by the mean RMS of the first five stable sessions in the same trajectory. This normalized RMS (NRMS) is found to be a good measure as it reflects the relative change in the total power of the signal, which elevates dramatically entering the STN. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Depression | before surgery and the 30days after surgery | Depression will be evaluated using Hamilton Depression Rating Scale (HAMD)，a score of 0 to 76,the higher score means a worse depression |
| Long-term Quality of sleep | before surgery and the 30days after surgery | Long-term quality of sleep will be evaluated with Pittsburgh Sleep Quality Index (PSQI) ,a score of 0 to 21, the higher score means a worse quality of sleep. |
| Beta band (13-30 Hz) oscillations calculated by spectrum analysis | 1 day (during MER recording) | Power spectrum will be calculated using a discrete Fourier transform of the sampling windows to allow evaluation of change in oscillatory activity along time. Synchronized beta band (13-30 Hz) oscillations are often observed in the dorsolateral region of the STN of PD patients and are thought to play a role in the disease pathophysiology. The power of beta band will be calculated by averaging the power across the corresponding frequency band. |
| Anxiety | before surgery and the 30days after surgery | Anxiety will be evaluated using Hamilton Anxiety Rating Scale (HAMA)，a score of 0 to 56，the higher score means a worse anxiety |
| Delirium Assessment: 3-Minute Diagnostic Interview for CAM (3D-CAM) | Postoperative 3 days and the 30th day | Postoperative delirium is assessed by the 3-minute diagnostic interview for CAM(3D-CAM),the score is 0 or 1, where 0 represents non-delirium and 1 represents delirium. |
| The incidence of anaesthesia-related adverse events | Up to 3 days after randomization] | Nausea, vomiting, excessive Secretions and intraoperative awareness |
| Surgical experience satisfaction 24 hours after the operation and DBS satisfaction 1 months after the operationevaluated by the seven-point Likert scale | 24 hours after operation for surgical experience satisfaction and 1 months after STN-DBS for DBS satisfaction | The seven-point Likert scale will be used in the present trial. It is a questionnaire answered by the patient 24 hoursafter the operation. The scale reported the experience of the patient from very dissatisfied to very satisfied, as graded from 1-7. |
| Early postoperative Quality of sleep | the first and the second and the third day after surgery | The early postoperative sleep quality will be monitored using a portable sleep monitor, with indicators including the duration of total sleep, the proportion of light sleep, deep sleep, and rapid eye movement (REM) sleep. |
Countries
China
Contacts
Primary ContactRuquan Han, MD,PhD
Outcome results
None listed