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

The Effects of Subanesthetic S-ketamine on Postoperative Delirium and Cognitive Function in the Elderly Undergoing Non-cardiac Thoracic Surgery: a Protocol for Randomized, Double-blinded, Positive-controlled, Non-inferiority Trial

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. Secondary outcomes included postoperative delirium severity, motroic subtypes, episodes, and duration. Additional prespecified outcomes were emergence delirium; time to delirium onset; time to extubation; postoperative pain intensity at rest and during cough at 4, 24, and 48 h postoperatively; postoperative opioid consumption and rescue analgesia requirements; subjective sleep quality within the initial 4 days after surgery; postoperative length of hospital stay; and cognitive function and mortality at 30- and 90-day follow-up.

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.