Long-term Follow-up of Dexmedetomidine-esketamine and tDCS for Neurocognitive Complications After Surgery

Summary

Neurocognitive complications, mainly delirium and neurocognitive disorders, are common cerebral complications in older patients after surgery and associated with worse long-term outcomes. An ongoing 2×2 factorial trial conducted by the investigators plan to test the effects of perioperative dexmedetomidine-esketamine combination and transcranial direct current stimulation (tDCS) on postoperative neurocognitive complications in older patients. This long-term follow-up of the ongoing trial aims to investigate the effects of perioperative dexmedetomidine-esketamine combination and tDCS on long-term outcomes in older patients after noncardiac surgery.

Conditions

• Older Patients
• Surgery
• Dexmedetomidine
• Esketamine
• Transcranial Direct Current Stimulation
• Cognitive Function
• Survival

Interventions

DRUG

Dex-Esk

Dexmedetomidine-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 expected end surgery. Postoperative patient-controlled analgesia will be established with a 100 mL mixture (containing 1.0 μg/mL sufentanil, 1.25 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).

DRUG

Placebo

Placebo (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 expected end 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).

DEVICE

Active tDCS

Active 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).

DEVICE

Sham tDCS

Sham 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).

Sponsors & Collaborators

• Peking University Shenzhen Hospital

  collaborator OTHER

• Second Affiliated Hospital, School of Medicine, Zhejiang University

  collaborator OTHER

• Fujian Medical University Union Hospital

  collaborator OTHER

• The First Affiliated Hospital of Air Force Medicial University

  collaborator OTHER

• Zhejiang University

  collaborator OTHER

• Peking University First Hospital

  lead OTHER

Principal Investigators

• Dong-Xin Wang, MD, PhD · Peking University First Hospital

Study Design

Allocation

RANDOMIZED

Purpose

PREVENTION

Masking

QUADRUPLE

Model

FACTORIAL

Eligibility

Min Age

65 Years

Max Age

90 Years

Sex

ALL

Healthy Volunteers

Yes

Timeline & Regulatory

Start

2026-06-30

Primary Completion

2030-06-30

Completion

2031-06-30

Countries

• China

Study Locations