Neurocognitive complications, mainly delirium and neurocognitive disorders, are common cerebral complications in older patients after surgery and associated with worse outcomes. In previous studies, perioperative use of dexmedetomidine-esketamine combination improved analgesia and sleep quality after surgery. Perioperative use of transcranial direct current stimulation (tDCS) also improved sleep quality and reduced delirium occurrence early after surgery. This 2×2 factorial trial is designed to investigate the effects of perioperative dexmedetomidine-esketamine combination and tDCS on delirium occurrence and early postoperative neurocognitive recovery in older patients.
Aged 65 years or higher;
Preoperative Mini-Cognitive Assessment (Mini-Cog) score ≤ 2 points, indicating possible cognitive impairment ranging from mild to moderate;
Scheduled to undergo elective non-cardiac, non-neurosurgical surgery under general anesthesia, with an expected surgical duration > 1 hour;
Required patient-controlled intravenous analgesia (PCIA) after surgery.
Preoperative inability to communicate due to coma, severe dementia, end-stage disease, or language impairment;
History of schizophrenia, epilepsy, Parkinson's disease, brain trauma/surgery, or myasthenia gravis;
Presence of metal implants in the intracranial or cervical region (such as cochlear implants, aneurysm clips, deep brain stimulation electrodes), or skin damage or severe skin disease on the head;
Severe cardiac dysfunction (left ventricular ejection fraction < 30%), comorbid with sick sinus syndrome, severe bradycardia (heart rate < 50 bpm), or second-degree or higher atrioventricular block, or implantation of a cardiac pacemaker;
Factorial
Dex-Esk
DrugDexmedetomidine-esketamine combination (1 μg/mL dexmedetomidine and 0.5 mg/mL esketamine) will be administered after anesthesia induction, firstly as a loading dose at a rate of \[0.4 x body weight (kg)\] mL/h for 30 minutes (0.2 μg/kg dexmedetomidine and 0.1 mg/kg esketamine), followed by a maintenance infusion at a rate of \[0.1 x body weight (kg)\] mL/h (0.1 μg/kg/h dexmedetomidine and 0.05 mg/kg/h esketamine) until one hour before the expected end of surgery. Postoperative patient-controlled analgesia will be established with a 100 mL mixture (containing 1.0 μg/mL sufentanil, 1.0 μg/mL dexmedetomidine, and 0.25 mg/mL esketamine in normal saline), programmed to deliver 2-mL boluses with an 8-minute lockout interval and an 1-mL/h background infusion, and provided for 48 hours (at least 24 hours).
Placebo
DrugPlacebo (normal saline) will be administered after anesthesia induction, firstly as a loading dose at a rate of \[0.4 x body weight (kg)\] mL/h for 30 minutes, followed by a maintenance infusion at a rate of \[0.1 x body weight (kg)\] mL/h until one hour before the expected end of surgery. Postoperative patient-controlled analgesia will be established with a 100 mL mixture (containing 1.0 μg/mL sufentanil in normal saline), programmed to deliver 2-mL boluses with an 8-minute lockout interval and an 1-mL/h background infusion, and provided for 48 hours (at least 24 hours).
Active tDCS
DeviceActive transcranial direct current stimulation (tDCS) will be administered using a battery-powered stimulator. The anode will be positioned over the left dorsolateral prefrontal cortex (DLPFC, F3) and the cathode over the right supraorbital region (Fp2). The stimulation intensity will be set at 2.0 mA, featuring a 30-second linear ramp-up at the beginning and a 30-second ramp-down at the end of each session. Each participant will receive a total of three 20-minute sessions of active tDCS. The first session will be provided at 40 minutes after extubation in the post-anesthesia care unit. Two other sessions will be provided on postoperative days 1 and 2 (between 10:00 and 12:00 am).
Sham tDCS
DeviceSham transcranial direct current stimulation (tDCS) will be administered using a battery-powered stimulator. The anode will be positioned over the left dorsolateral prefrontal cortex (DLPFC, F3) and the cathode over the right supraorbital region (Fp2). To ensure blinding, the device will deliver a initial 30-second ramp-up to 2.0 mA followed immediately by a 30-second ramp-down to 0 mA. The device remains "ON" for the remaining 19 minutes with no effective current output, mimicking the peripheral scalp sensation without delivering cortical modulation. Each participant will receive a total of three 20-minute sessions of sham tDCS. The first session will be provided at 40 minutes after extubation in the post-anesthesia care unit. Two other sessions will be provided on postoperative days 1 and 2 (between 10:00 and 12:00 am).
Incidence of postoperative delirium (POD)
Delirium will be assessed twice daily (8-10 am and 6-8 pm) using the 3-Dimensional Confusion Assessment Method (3D-CAM) for patients without intubation or the Confusion Assessment Method for the Intensive Care Unit (CAM-ICU) for patients with intubation.
Days at home within 30 days after surgery (DAH-30)
Defined as the number of days within 30 days after surgery that the patient is alive and living at home (or other usual place of residence), calculated as 30 days minus days spent in postoperative hospitalization, readmission, rehabilitation facility, nursing facility, or other non-home institutional stays.
Incidence of postoperative neurocognitive disorders (pNCD)
Cognitive function will be assessed at baseline using the Montreal Cognitive Assessment (MoCA; scores range from 0 to 30, with higher scores indicating better cognitive function) and at 30 days after surgery using the Telephone MoCA (T-MoCA; scores range from 0 to 22, with higher scores indicating better cognitive function). Postoperative neurocognitive disorders (pNCD) is defined as T-MoCA score decreased by ≥1 SD from baseline.
POD severity cumulative score
The cumulative score of the severity score at each assessment time point in 3D-CAM-S/CAM-ICU-7 (the cumulative score of the severity score at all assessment time points on days 1-4 after surgery, to reflect both the intensity and duration of POD symptoms) is used as the measurement index.
POD motor subtype
According to the RASS score, POD is divided into high activity type (RASS 1\~4 points), low activity type (RASS -3\~0 points) and mixed type (the two appear alternately).
POD duration
Expressed as the number of postoperative CAM positive days.
Early postoperative subjective sleep quality
Subjective sleep quality will be assessed once daily (8-10 am) using PROMIS Short Form v1.0 - Sleep Disturbance 4a up to 4 nights after surgery.
Click on the lead sponsor to view all of their trials.
Peking University First Hospital
Lead sponsor
Peking University Shenzhen Hospital
Collaborator
The First Affiliated Hospital of Air Force Medicial University
Collaborator
First Affiliated Hospital of Zhejiang University
Collaborator
Second Affiliated Hospital, Zhejiang University, School of Medicine
Collaborator
Fujian Medical University Union Hospital
Collaborator
This trial is not recruiting at the moment. You can still explore other options:
