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

Neurocognitive complications, mainly delirium and neurocognitive disorders, are common cerebral complications in older patients after surgery. Occurrence of neurocognitive complications is associated with prolonge hospital stay and increased in-hospital death. Furthermore, occurrence of neurocognitive complications is associated with adverse long-term outcomes, including cognitive decline, poor quality of life, and reduced long-term survival. Dexmedetomidine is a highly selective alpha 2 adrenergic receptor agonist with sedative, analgesic, and anxiolytic effects. Available evidence showed that perioperative dexmedetomidine decreased early postoperative neurocognitive complications in older patients, possibly by improving analgesia and sleep quality and relieving surgery-related inflammation. However, routine dose dexmedetomidine increases bradycardia and hypotension which are potentially harmful to older patients. Ketamine is a noncompetitive N-Methyl-D-aspartic acid (NMDA) receptor antagonist and has been used as an anesthetic and analgesic for decades. Esketamine is the S-enantiomer of ketamine and twice as potent as racemic ketamine. Recent studies found that subanesthetic dose of esketamine is effective in improving analgesia and sleep quality and relieving surgery-related stress response. However, even subanesthetic ketamine or esketamine increases neuropsychiatric side effects. In clinical practice, dexmedetomidine-esketamine combination has been used for premedication in children and postoperative analgesia in adults and showed additive or synergistic effects. An ongoing trial conducted by the investigators plan to test the hypothesis that perioperative use of dexmedetomidine-esketamine combination may prevent postoperative neurocognitive complications in older patients. It is reasonable to hypothesize that perioperative dexmedetomdine-esketamine might also have favorable effects on long-term outcomes. Transcranial direct current stimulation (tDCS) is a non-invasive neuromodulation technique and increasingly used for treatment of various neurological diseases. Studies in the perioperative settings showed that perioperative use of tDCS improved sleep quality and reduced delirium occurrence early after surgery. The ongoing trial coducted by the investigators plan to test the hypothesis that perioperative use of tDCS may reduce postoperative neurocognitive complications in older patients. Perioperative tDCS might also have favorable effects on long-term outcomes. This long-term follow-up of the ongoing 2×2 factorial trial aims to investigate the effects of perioperative dexmedetomidine-esketamine combination and tDCS on long-term outcomes in older patients after noncardiac surgery.