Clinical trial NCT06900205: Effects of Esketamine on the Incidence of Postoperative Delirium and Postoperative Sleep Disturbance in Elderly Patients After Major Non-cardiac Surgery
Official title: Effects of Esketamine on the Incidence of Postoperative Delirium and Postoperative Sleep Disturbance in Elderly Patients After Major Non-cardiac Surgery: A Multi-Center Randomized Controlled Trial
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: NA
Conditions: Postoperative Delirium (POD)
Postoperative Sleep Disturbance
Keywords: esketamine
non-cardiac surgery
Postoperative Delirium (POD)
Postoperative Sleep Disturbance
Lead sponsor: RenJi Hospital
Sponsor class: OTHER
Collaborators: name: Shanghai Chest Hospital
name: Shanghai Xuhui Central Hospital
First posted: 2025-03-28
Enrollment: 0
Sex: ALL
Minimum age (years): 65
Standard ages: OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Drug: Esketamine After anesthesia induction intubation and before surgery,0.25mg/kg esketamine will be diluted into a 10ml syringe and injected intravenously.

After surgery,a postoperative intravenous analgesia pump will be given with the following drugs and dosages:sufentanil 1.5ug/kg,esketaminge 1.0mg/kg and tolansetron 5mg, diluted into100ml at 2ml/h for 48h.

Drug: 0.9% saline After anesthesia induction intubation and before surgery,10ml of 0.9% saline will be injected intravenously.

After surgery,a postoperative intravenous analgesia pump will be given with the following drugs and dosages:sufentanil 1.5ug/kg and tolansetron 5mg, diluted into100ml at 2ml/h for 48h.
Primary purpose: PREVENTION

Brief summary: Postoperative delirium (POD) is a common surgical complication.It is associated with a range of negative outcomes such as delayed postoperative recovery,prolonged hospitalization,additional medical expenditures and higher mortality.

Meanwhile,sleep disorders are not only an important predisposing factor for delirium,but also one of the main symptoms of delirium.Systemic inflammatory responses caused by sleep disorders may be an important mechanism for POD.

Many studies have shown that esketamie may inhibit inflammatory factors and enhance neuroplasticity.

In summary,we felt the need to further explore the therapeutic potential of esketamine in the area of POD as well as postoperative sleep disorders.


Eligibility criteria: Inclusion Criteria:

1. Age ≧ 65 years;
2. ASA Ⅰ-Ⅲ;
3. Elective major non-cardiac surgery;
4. Voluntary signed informed consent.

Exclusion Criteria:

1. People with mental illness;
2. Suffering from serious central nervous system disorders such as arkinson's disease, Alzheimer's disease, etc;
3. Elevated intracranial pressure;
4. Emergency or trauma surgery;
5. Prior history of postoperative delirium or postoperative cognitive decline;
6. The patient has impaired hearing or impaired vision;
7. Suffering from severe systemic underlying diseases (e.g. cardiac insufficiency, malignant arrhythmia, malignant hypertension, hepatic failure, renal failure, etc.);
8. The patient is in chronic pain;
9. The patient is severely malnourished;
10. Patients with stage 3 or 4 malignant tumors, pancreatic cancer, allbladder cancer, cholangiocarcinoma and other tumors with high malignancy and poor prognosis.
11. history of allergy to or contraindication to esketamine;
12. inability or unwillingness to complete questionnaires or clinical testing;
13. Unable or unwilling to use a postoperative intravenous analgesic pump.

Primary outcomes:
measure: The incidence of postoperative delirium
timeFrame: postoperative 7 day
measure: The incidence of postoperative sleep disturbance
timeFrame: postoperative 3 day
Secondary outcomes:
measure: The incidence of postoperative cognitive dysfunction
timeFrame: 7 days after surgery and 90 days after surgery
measure: postoperative pain severity score
timeFrame: 2 hours after surgery、postoperative 3 day and 90 days after surgery
measure: The incidence of postoperative adverse reactions
timeFrame: postoperative 90 days
Other outcomes:
Locations:
city: Shanghai
country: China
facility: Renji Hospital, Shanghai Jiao Tong University School of Medicine
state: Shanghai
Study officials:
References:
citation: Xiong X, Shao Y, Chen D, Chen B, Lan X, Shi J. Effect of Esketamine on Postoperative Delirium in Patients Undergoing Cardiac Valve Replacement with Cardiopulmonary Bypass: A Randomized Controlled Trial. Anesth Analg. 2024 Oct 1;139(4):743-753. doi: 10.1213/ANE.0000000000006925. Epub 2024 Mar 6.
citation: Luo T, Deng Z, Ren Q, Mu F, Zhang Y, Wang H. Effects of esketamine on postoperative negative emotions and early cognitive disorders in patients undergoing non-cardiac thoracic surgery: A randomized controlled trial. J Clin Anesth. 2024 Aug;95:111447. doi: 10.1016/j.jclinane.2024.111447. Epub 2024 Mar 23.
citation: Zhang A, Zhou Y, Zheng X, Zhou W, Gu Y, Jiang Z, Yao Y, Wei W. Effects of S-ketamine added to patient-controlled analgesia on early postoperative pain and recovery in patients undergoing thoracoscopic lung surgery: A randomized double-blinded controlled trial. J Clin Anesth. 2024 Feb;92:111299. doi: 10.1016/j.jclinane.2023.111299. Epub 2023 Nov 7.
citation: Sadeghirad B, Dodsworth BT, Schmutz Gelsomino N, Goettel N, Spence J, Buchan TA, Crandon HN, Baneshi MR, Pol RA, Brattinga B, Park UJ, Terashima M, Banning LBD, Van Leeuwen BL, Neerland BE, Chuan A, Martinez FT, Van Vugt JLA, Rampersaud YR, Hatakeyama S, Di Stasio E, Milisen K, Van Grootven B, van der Laan L, Thomson Mangnall L, Goodlin SJ, Lungeanu D, Denhaerynck K, Dhakharia V, Sampson EL, Zywiel MG, Falco L, Nguyen AV, Moss SJ, Krewulak KD, Jaworska N, Plotnikoff K, Kotteduwa-Jayawarden S, Sandarage R, Busse JW, Mbuagbaw L. Perioperative Factors Associated With Postoperative Delirium in Patients Undergoing Noncardiac Surgery: An Individual Patient Data Meta-Analysis. JAMA Netw Open. 2023 Oct 2;6(10):e2337239. doi: 10.1001/jamanetworkopen.2023.37239.
citation: Mevorach L, Forookhi A, Farcomeni A, Romagnoli S, Bilotta F. Perioperative risk factors associated with increased incidence of postoperative delirium: systematic review, meta-analysis, and Grading of Recommendations Assessment, Development, and Evaluation system report of clinical literature. Br J Anaesth. 2023 Feb;130(2):e254-e262. doi: 10.1016/j.bja.2022.05.032. Epub 2022 Jul 7.
citation: Sprung J, Roberts RO, Weingarten TN, Nunes Cavalcante A, Knopman DS, Petersen RC, Hanson AC, Schroeder DR, Warner DO. Postoperative delirium in elderly patients is associated with subsequent cognitive impairment. Br J Anaesth. 2017 Aug 1;119(2):316-323. doi: 10.1093/bja/aex130.
citation: Qiu D, Wang XM, Yang JJ, Chen S, Yue CB, Hashimoto K, Yang JJ. Effect of Intraoperative Esketamine Infusion on Postoperative Sleep Disturbance After Gynecological Laparoscopy: A Randomized Clinical Trial. JAMA Netw Open. 2022 Dec 1;5(12):e2244514. doi: 10.1001/jamanetworkopen.2022.44514.
citation: Avidan MS, Maybrier HR, Abdallah AB, Jacobsohn E, Vlisides PE, Pryor KO, Veselis RA, Grocott HP, Emmert DA, Rogers EM, Downey RJ, Yulico H, Noh GJ, Lee YH, Waszynski CM, Arya VK, Pagel PS, Hudetz JA, Muench MR, Fritz BA, Waberski W, Inouye SK, Mashour GA; PODCAST Research Group. Intraoperative ketamine for prevention of postoperative delirium or pain after major surgery in older adults: an international, multicentre, double-blind, randomised clinical trial. Lancet. 2017 Jul 15;390(10091):267-275. doi: 10.1016/S0140-6736(17)31467-8. Epub 2017 May 30.