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

Postoperative Delirium Clinical Trial

— SKED  

Official title:

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, placebo-and Positive-controlled, Non-inferiority Trial

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05242692
• Other study ID #: ATHGuangzhou
• Status: Recruiting
• Phase: Early Phase 1
• Start date: March 10, 2022
• Est. completion date: February 28, 2024

Study information

• Verified date: January 2023
• Source: Affiliated Cancer Hospital & Institute of Guangzhou Medical University
• Contact: WEI WEI, MD
• Phone: +8618520698366
• Email: 1575041594[@]qq.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Description:

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 780
• Est. completion date: February 28, 2024
• Est. primary completion date: December 31, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 60 Years to 90 Years

Eligibility

Inclusion Criteria:

• Aged 60 years or over

• Both genders

• American anesthesiologist association (ASA) physical status classification?-?

• 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 ? 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.

Related Conditions & MeSH terms

• Delirium
• Elderly Patients
• Postoperative Delirium

Intervention

Drug:
• S-ketamine
Loading dose: 0.25mg/kg in 10 minutes Maintenance dose: 0.1mg/kg/h
• Dexmedetomidine
Loading dose: 0.2 ug/kg in 10 minutes Maintenance dose: 0.2 ug/kg/h
• Normal saline
Refer to either S-ketamine or Dexmedetomidine

Locations

Country	Name	City	State
China	Cancer hospital and institute of Guangzhou medical university	Guangzhou	Guangdong

Sponsors (1)

Lead Sponsor	Collaborator
Affiliated Cancer Hospital & Institute of Guangzhou Medical University

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Emergency delirium	Richard Agitation-Sedation Scale (RASS) (RASS score = 1 indicates emergency delirium, the higher scores mean a worse outcome.)	From 30 minutes after the arrival in the post anesthesia care unit (PACU) until the time-point of PACU discharge, assessed up to 2 hours
Other	Pain severity	Numeric rating scale (NRS)0 = [no pain], 0 < NRS < 4 [mild pain], 4 = NRS < 7 [moderate pain], 7 = NRS <10 [severe pain], NRS = 10 [worst pain imaginable]	Within 2 days after surgery
Other	Quality of sleep	Numeric rating scale(0 = best-quality sleep, 10 = worst-quality sleep)	Within 4 days after surgery
Other	Cognitive function	Telephone interview for cognitive status-40 (TICS-40); A score below 21 will be defined as mild cognitive impairment, the higher scores mean a worse outcome.	On postoperative day 30
Other	Cognitive function	Telephone interview for cognitive status-40 (TICS-40); A score below 21 will be defined as mild cognitive impairment, the higher scores mean a worse outcome.	On postoperative day 60
Other	Concentration of plasma acetylcholine (ACh)	Enzyme-linked immunosorbent assay (ELISA) method	Within 5 minutes before induction
Other	Concentration of plasma acetylcholine (ACh)	Enzyme-linked immunosorbent assay (ELISA) method	Within 5 minutes after the end of skin closure
Other	Concentration of plasma acetylcholine (ACh)	Enzyme-linked immunosorbent assay (ELISA) method	On postoperative day 4
Other	Concentration of plasma brain deprived neurotrophic factor (BDNF)	Enzyme-linked immunosorbent assay (ELISA) method	Within 5 minutes before induction
Other	Concentration of plasma brain deprived neurotrophic factor (BDNF)	Enzyme-linked immunosorbent assay (ELISA) method	Within 5 minutes after the end of skin closure
Other	Concentration of plasma brain deprived neurotrophic factor (BDNF)	Enzyme-linked immunosorbent assay (ELISA) method	On postoperative day 4
Other	Concentration of plasma tumor necrosis factor (TNF)	Enzyme-linked immunosorbent assay (ELISA) method	Within 5 minutes before induction
Other	Concentration of plasma tumor necrosis factor (TNF)	Enzyme-linked immunosorbent assay (ELISA) method	Within 5 minutes after the end of skin closure
Other	Concentration of plasma tumor necrosis factor (TNF)	Enzyme-linked immunosorbent assay (ELISA) method	On postoperative day 4
Primary	Number of Patients With Post-operative Delirium in 4 Days After Surgery	3-minute Diagnostic Confusion Assessment Method (3D-CAM)	Within 4 days after surgery
Secondary	Severity of Delirium	Confusion Assessment Method- Severity (CAM-S, Mild-to-moderate delirium will be defined as a CAM-S score of 3 to 5, while severe delirium will be defined as a CAM-S score of 6 to 7)	Within 4 days after surgery
Secondary	Duration of postoperative delirium	Positive days of postoperative delirium	Within 4 days after surgery