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

Primary Purpose

Postoperative Delirium, Elderly Patients

Status

Recruiting

Phase

Early Phase 1

Locations

China

Study Type

Interventional

Intervention

S-ketamine

Dexmedetomidine

Normal saline

About this trial

This is an interventional prevention trial for Postoperative Delirium focused on measuring Postoperative delirium, S-ketamine, Dexmedetomidine, elderly patients

Eligibility Criteria

60 Years - 90 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

Cancer hospital and institute of Guangzhou medical universityRecruiting

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Active Comparator

Placebo Comparator

Arm Label

S-ketamine

Dexmedetomidine

Normal saline

Arm Description

S-ketamine (50 mg, 2 ml) is diluted to 50 ml (1 mg/ml) with 48 ml normal saline;

Dexmedetomidine (200 ug, 2 ml) is diluted to 100 ml (2 ug/ml) with 98 ml normal saline;

Control group only contains 50 ml normal saline in light of blindness

Outcomes

Primary Outcome Measures

Number of Patients With Post-operative Delirium in 4 Days After Surgery

3-minute Diagnostic Confusion Assessment Method (3D-CAM)

Secondary Outcome Measures

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)

Duration of postoperative delirium

Positive days of postoperative delirium

Full Information

NCT ID

NCT05242692

First Posted

December 23, 2021

Last Updated

February 16, 2023

Sponsor

Affiliated Cancer Hospital & Institute of Guangzhou Medical University

1. Study Identification

Unique Protocol Identification Number

NCT05242692

Brief Title

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

Acronym

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

Study Type

Interventional

2. Study Status

Record Verification Date

January 2023

Overall Recruitment Status

Recruiting

Study Start Date

March 10, 2022 (Actual)

Primary Completion Date

December 31, 2023 (Anticipated)

Study Completion Date

February 28, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Affiliated Cancer Hospital & Institute of Guangzhou Medical University

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Product Manufactured in and Exported from the U.S.

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

Detailed 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Postoperative Delirium, Elderly Patients

Keywords

Postoperative delirium, S-ketamine, Dexmedetomidine, elderly patients

7. Study Design

Primary Purpose

Prevention

Study Phase

Early Phase 1

Interventional Study Model

Parallel Assignment

Masking

ParticipantCare ProviderInvestigatorOutcomes Assessor

Masking Description

The labeled "Study medication" syringes (50ml) in identical appearance, and the infusion regimen formulated by the pharmacist based on the randomization, will be distributed to the attending anesthesiologists responsible for anesthetic management as soon as the research team informs the central pharmacy about the patient heading for surgery. To avoid anesthesiologists' speculation about the randomized assignment, the study drugs will be infused at a similar rate. The anesthesiologists, the patients, the investigators responsible for follow-up, and the statisticians are all masked to randomized allocations until the final statistical analyses are completed. The blindness will be unmasked by the primary investigator in a medical emergency including deterioration of patient's condition intraoperatively or adverse events postoperatively.

Allocation

Randomized

Enrollment

780 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

S-ketamine

Arm Type

Experimental

Arm Description

S-ketamine (50 mg, 2 ml) is diluted to 50 ml (1 mg/ml) with 48 ml normal saline;

Arm Title

Dexmedetomidine

Arm Type

Active Comparator

Arm Description

Dexmedetomidine (200 ug, 2 ml) is diluted to 100 ml (2 ug/ml) with 98 ml normal saline;

Arm Title

Normal saline

Arm Type

Placebo Comparator

Arm Description

Control group only contains 50 ml normal saline in light of blindness

Intervention Type

Drug

Intervention Name(s)

S-ketamine

Intervention Description

Loading dose: 0.25mg/kg in 10 minutes Maintenance dose: 0.1mg/kg/h

Intervention Type

Drug

Intervention Name(s)

Dexmedetomidine

Intervention Description

Loading dose: 0.2 ug/kg in 10 minutes Maintenance dose: 0.2 ug/kg/h

Intervention Type

Drug

Intervention Name(s)

Normal saline

Intervention Description

Refer to either S-ketamine or Dexmedetomidine

Primary Outcome Measure Information:

Title

Number of Patients With Post-operative Delirium in 4 Days After Surgery

Description

3-minute Diagnostic Confusion Assessment Method (3D-CAM)

Time Frame

Within 4 days after surgery

Secondary Outcome Measure Information:

Title

Severity of Delirium

Description

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)

Time Frame

Within 4 days after surgery

Title

Duration of postoperative delirium

Description

Positive days of postoperative delirium

Time Frame

Within 4 days after surgery

Other Pre-specified Outcome Measures:

Title

Emergency delirium

Description

Richard Agitation-Sedation Scale (RASS) (RASS score ≥ 1 indicates emergency delirium, the higher scores mean a worse outcome.)

Time Frame

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

Title

Pain severity

Description

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]

Time Frame

Within 2 days after surgery

Title

Quality of sleep

Description

Numeric rating scale(0 = best-quality sleep, 10 = worst-quality sleep)

Time Frame

Within 4 days after surgery

Title

Cognitive function

Description

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.

Time Frame

On postoperative day 30

Title

Cognitive function

Description

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.

Time Frame

On postoperative day 60

Title

Concentration of plasma acetylcholine (ACh)

Description