The Effects of Subanesthetic S-ketamine on Postoperative Delirium and Cognitive Function in the Elderly Undergoing Non-cardiac Thoracic Surgery

Postoperative delirium (POD) is a common and distressing complication after thoracic surgery. S-ketamine has neuroprotective properties as a dissociative anesthetic. Emerging literature has indicated that S-ketamine can reduce cognitive impairment in depressed patients. However, the role of S-ketamine in preventing postoperative delirium is still unknown. Therefore, this study aims to evaluate the effect of intraoperatively prophylactic S-ketamine compared to dexmedetomidine on the incidence of postoperative delirium in elderly patients undergoing non-cardiac thoracic surgery.

Postoperative delirium (POD) is a common and distressing complication after thoracic surgery. S-ketamine has neuroprotective properties as a dissociative anesthetic. Emerging literature has indicated that S-ketamine can reduce cognitive impairment in depressed patients. However, the role of S-ketamine in preventing postoperative delirium is still unknown. Therefore, this study aims to evaluate the effect of intraoperatively prophylactic S-ketamine compared to dexmedetomidine on the incidence of postoperative delirium in elderly patients undergoing non-cardiac thoracic surgery. This will be a randomized, double-blinded, placebo-and positive-controlled, non-inferiority trial that enrolls patients aged 60 or over undergoing thoracic surgery. The primary outcome will be the incidence of postoperative delirium within 4 days after surgery and assessed using a 3-minute Diagnostic Confusion Assessment Method (3D-CAM) twice a day. The main secondary outcomes will be the severity and duration of postoperative delirium. Other prespecified secondary outcomes will be the incidence of emergency delirium, postoperative pain, quality of sleep, cognitive function, and the plasm concentration of acetylcholine, brain-derived neurotrophic factor, and tumor necrosis factor.

Eligibility Criteria:
Inclusion Criteria:

* Aged 60 years or over
* Both genders
* American anesthesiologist association (ASA) physical status classificationⅠ-Ⅲ
* Diagnosed with lung, esophagus, or mediastinum disorders
* Undergoing open or video-assisted thoracic surgery including lobectomy, segmentectomy, pneumonectomy, esophagectomy, or resection of mediastinal tumor
* General anesthesia with one-lung ventilation (OLV) or bronchial blocker.
* An expected operation duration of 2 hours or more.
* Voluntarily participate in the trial and sign informed consent.

Exclusion Criteria:

* History of psychiatric disease or severe depression
* History of glaucoma or hyperthyroidism
* History of severe hepatic (Child-Pugh grade C) or renal (requirement for renal replacement therapy) disorder.
* Body mass index (BMI) greater 35 kg/m2
* Dementia history or baseline Mini-Mental State Examination (MMSE) score less than 23
* Severe audio-visual impairments, or inability to speak Mandarin or Cantonese precluding communication
* Sinus bradycardia (heart rate \< 50 beats per minutes, bpm), sick sinus or Wolff- Parkinson-White syndromes, or Ⅱ degree atrioventricular block and over
* Poorly controlled hypertension (resting systolic blood pressure over 180 mm Hg, or resting diastolic blood pressure over 100 mm Hg)
* Allergic to dexmedetomidine, S-ketamine or any of their formulation ingredients;
* Taking sedatives, antidepressants or glucocorticoids
* Alcohol or drug abuser
* Life expectancy of less than 2 months due to extensive tumor metastasis.