drugset / Trial / NCT07576517
Dexmedetomidine-esketamine and tDCS for Prevention of Neurocognitive Complications After Surgery
Phase 4
Not yet recruiting
1160 enrolled
Peking University First Hospital
Fujian Medical University Union Hospital · collabPeking University Shenzhen Hospital · collabSecond Affiliated Hospital, School of Medicine, Zhejiang University · collabThe First Affiliated Hospital of Air Force Medicial University · collabZhejiang University · collab
RandomizedFactorialQuadruple-blindPrevention
Summary
Neurocognitive complications, mainly delirium and neurocognitive disorders, are common cerebral complications in older patients after surgery and associated with worse outcomes. In previous studies, perioperative use of dexmedetomidine-esketamine combination improved analgesia and sleep quality after surgery. Perioperative use of transcranial direct current stimulation (tDCS) also improved sleep quality and reduced delirium occurrence early after surgery. This 2×2 factorial trial is designed to investigate the effects of perioperative dexmedetomidine-esketamine combination and tDCS on early postoperative neurocognitive recovery and delirium occurrence in older patients.
Timeline
- Start
- 2026-06
- Primary completion
- 2029-06
- Completion
- 2030-06
Publications
- Background Eisenhauer EA, Therasse P, Bogaerts J, Schwartz LH, Sargent D, Ford R, Dancey J, Arbuck S, Gwyther S, Mooney M, Rubinstein L, Shankar L, Dodd L, Kaplan R, Lacombe D, Verweij J. New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer. 2009 Jan;45(2):228-47. doi: 10.1016/j.ejca.2008.10.026.
- Background Tao M, Yang J, Liu R, Zhang S, Han Y, Li C, Wei Q, Chen D, Fang J, Zhang H, Wang Y, Liu H, Cao JL. Efficacy of transcranial direct current stimulation for improving postoperative quality of recovery in elderly patients undergoing lower limb major arthroplasty: a randomized controlled substudy. Front Neurol. 2024 Jan 24;15:1327558. doi: 10.3389/fneur.2024.1327558. eCollection 2024.
- Background Rodrigues NB, McIntyre RS, Lipsitz O, Lee Y, Cha DS, Shekotikhina M, Vinberg M, Gill H, Subramaniapillai M, Kratiuk K, Lin K, Ho R, Mansur RB, Rosenblat JD. A simplified 6-Item clinician administered dissociative symptom scale (CADSS-6) for monitoring dissociative effects of sub-anesthetic ketamine infusions. J Affect Disord. 2021 Mar 1;282:160-164. doi: 10.1016/j.jad.2020.12.119. Epub 2020 Dec 29.
- Background Shinall MC Jr, Arya S, Youk A, Varley P, Shah R, Massarweh NN, Shireman PK, Johanning JM, Brown AJ, Christie NA, Crist L, Curtin CM, Drolet BC, Dhupar R, Griffin J, Ibinson JW, Johnson JT, Kinney S, LaGrange C, Langerman A, Loyd GE, Mady LJ, Mott MP, Patri M, Siebler JC, Stimson CJ, Thorell WE, Vincent SA, Hall DE. Association of Preoperative Patient Frailty and Operative Stress With Postoperative Mortality. JAMA Surg. 2020 Jan 1;155(1):e194620. doi: 10.1001/jamasurg.2019.4620. Epub 2020 Jan 15.
- Background Zisapel N, Nir T. Determination of the minimal clinically significant difference on a patient visual analog sleep quality scale. J Sleep Res. 2003 Dec;12(4):291-8. doi: 10.1046/j.0962-1105.2003.00365.x.
- Background Martin S, Chandran A, Zografos L, Zlateva G. Evaluation of the impact of fibromyalgia on patients' sleep and the content validity of two sleep scales. Health Qual Life Outcomes. 2009 Jul 10;7:64. doi: 10.1186/1477-7525-7-64.
- Background Buysse DJ, Reynolds CF 3rd, Monk TH, Berman SR, Kupfer DJ. The Pittsburgh Sleep Quality Index: a new instrument for psychiatric practice and research. Psychiatry Res. 1989 May;28(2):193-213. doi: 10.1016/0165-1781(89)90047-4.
- Background Wang W, Bian Q, Zhao Y, Li X, Wang W, Du J, Zhang G, Zhou Q, Zhao M. Reliability and validity of the Chinese version of the Patient Health Questionnaire (PHQ-9) in the general population. Gen Hosp Psychiatry. 2014 Sep-Oct;36(5):539-44. doi: 10.1016/j.genhosppsych.2014.05.021. Epub 2014 Jun 6.
- Background Lawton MP, Brody EM. Assessment of older people: self-maintaining and instrumental activities of daily living. Gerontologist. 1969 Autumn;9(3):179-86. No abstract available.
- Background Lai Y, Zhao M, Jiang C, Du X, Wang Z, Zhang J, Bai Y, Xu B, Zhang W, Tang R, Sang C, Long D, Dong J, Ma C. Validation of T-MoCA in the Screening of Mild Cognitive Impairment in Chinese Patients With Atrial Fibrillation. Front Cardiovasc Med. 2022 Jun 22;9:896846. doi: 10.3389/fcvm.2022.896846. eCollection 2022.
- Background Wong A, Nyenhuis D, Black SE, Law LS, Lo ES, Kwan PW, Au L, Chan AY, Wong LK, Nasreddine Z, Mok V. Montreal Cognitive Assessment 5-minute protocol is a brief, valid, reliable, and feasible cognitive screen for telephone administration. Stroke. 2015 Apr;46(4):1059-64. doi: 10.1161/STROKEAHA.114.007253. Epub 2015 Feb 19.
- Background Nasreddine ZS, Phillips NA, Bedirian V, Charbonneau S, Whitehead V, Collin I, Cummings JL, Chertkow H. The Montreal Cognitive Assessment, MoCA: a brief screening tool for mild cognitive impairment. J Am Geriatr Soc. 2005 Apr;53(4):695-9. doi: 10.1111/j.1532-5415.2005.53221.x.
- Background Creavin ST, Wisniewski S, Noel-Storr AH, Trevelyan CM, Hampton T, Rayment D, Thom VM, Nash KJ, Elhamoui H, Milligan R, Patel AS, Tsivos DV, Wing T, Phillips E, Kellman SM, Shackleton HL, Singleton GF, Neale BE, Watton ME, Cullum S. Mini-Mental State Examination (MMSE) for the detection of dementia in clinically unevaluated people aged 65 and over in community and primary care populations. Cochrane Database Syst Rev. 2016 Jan 13;2016(1):CD011145. doi: 10.1002/14651858.CD011145.pub2.
- Background Kunicki ZJ, Ngo LH, Marcantonio ER, Tommet D, Feng Y, Fong TG, Schmitt EM, Travison TG, Jones RN, Inouye SK. Six-Year Cognitive Trajectory in Older Adults Following Major Surgery and Delirium. JAMA Intern Med. 2023 May 1;183(5):442-450. doi: 10.1001/jamainternmed.2023.0144.
- Background Li C, Tao M, Chen D, Wei Q, Xiong X, Zhao W, Tan W, Yang J, Han Y, Zhang H, Zhang S, Liu H, Cao JL. Transcranial Direct Current Stimulation for Anxiety During Laparoscopic Colorectal Cancer Surgery: A Randomized Clinical Trial. JAMA Netw Open. 2024 Apr 1;7(4):e246589. doi: 10.1001/jamanetworkopen.2024.6589.
- Background Granger KT, Spies C, Caswell S, Hadzidiakos D, Speidel S, Slooter AJ, Kant I, Piper SK, van Montfort SJ, Barnett JH, Moran PM, Borchers F. Pre-surgical memory impairment is associated with risk of postoperative cognitive dysfunction in a large geriatric cohort. JAR Life. 2025 Feb 7;14:100002. doi: 10.1016/j.jarlif.2025.100002. eCollection 2025.
- Background Tao M, Zhang S, Han Y, Li C, Wei Q, Chen D, Zhao Q, Yang J, Liu R, Fang J, Li X, Zhang H, Liu H, Cao JL. Efficacy of transcranial direct current stimulation on postoperative delirium in elderly patients undergoing lower limb major arthroplasty: A randomized controlled trial. Brain Stimul. 2023 Jan-Feb;16(1):88-96. doi: 10.1016/j.brs.2023.01.839. Epub 2023 Jan 20.
- Background Yang X, Wei YF, Ye CH, Tian WD, Li XY, Hu YJ, Chen LP. Effect of preoperative transcranial direct current stimulation on postoperative delirium in elderly patients following laparoscopic surgery. World J Psychiatry. 2025 Oct 19;15(10):107298. doi: 10.5498/wjp.v15.i10.107298. eCollection 2025 Oct 19.
- Background Zahed M, El Menawy Z, Elmesalmi M, Elnaggar N, Ahmed F, Azaz RM, Elkilany A, Elhabbak SI, Amer SH, Adel M. Non-pharmacological Perioperative Interventions for the Prevention of Postoperative Delirium in Elderly Patients Undergoing Hip and Knee Arthroplasty Surgery: A Systematic Review. Cureus. 2025 Dec 17;17(12):e99475. doi: 10.7759/cureus.99475. eCollection 2025 Dec.
- Background Yang J, Tao M, Liu R, Fang J, Li C, Chen D, Wei Q, Xiong X, Zhao W, Tan W, Han Y, Zhang H, Liu H, Zhang S, Cao J. Effect of transcranial direct current stimulation on postoperative sleep disturbance in older patients undergoing lower limb major arthroplasty: a prospective, double-blind, pilot, randomised controlled trial. Gen Psychiatr. 2024 Mar 27;37(2):e101173. doi: 10.1136/gpsych-2023-101173. eCollection 2024.
- Background Prathum T, Chantanachai T, Vimolratana O, Laksanaphuk C, Apiworajirawit I, Aneksan B, Latthirun K, Yang CT, Klomjai W. A systematic review and meta-analysis of the impact of transcranial direct current stimulation on cognitive function in older adults with cognitive impairments: the influence of dosage parameters. Alzheimers Res Ther. 2025 Feb 4;17(1):37. doi: 10.1186/s13195-025-01677-y.
- Background Gomez-Garcia N, Alvarez-Barrio L, Leiros-Rodriguez R, Soto-Rodriguez A, Andrade-Gomez E, Hernandez-Lucas P. Transcranial direct current stimulation for post-stroke dysphagia: a meta-analysis. J Neuroeng Rehabil. 2023 Dec 11;20(1):165. doi: 10.1186/s12984-023-01290-w.
- Background Salehinejad MA, Ghanavati E, Glinski B, Hallajian AH, Azarkolah A. A systematic review of randomized controlled trials on efficacy and safety of transcranial direct current stimulation in major neurodevelopmental disorders: ADHD, autism, and dyslexia. Brain Behav. 2022 Sep;12(9):e2724. doi: 10.1002/brb3.2724. Epub 2022 Aug 8.
- Background Cocco S, Podda MV, Grassi C. Role of BDNF Signaling in Memory Enhancement Induced by Transcranial Direct Current Stimulation. Front Neurosci. 2018 Jun 26;12:427. doi: 10.3389/fnins.2018.00427. eCollection 2018.
- Background Zhang H, Zheng X, Zhang B. Anti-Inflammatory Pathways Mediating tDCS's Effects on Neuropathic Pain. Biology (Basel). 2025 Jul 20;14(7):892. doi: 10.3390/biology14070892.
- Background Shin DW, Fan J, Luu E, Khalid W, Xia Y, Khadka N, Bikson M, Fu BM. In Vivo Modulation of the Blood-Brain Barrier Permeability by Transcranial Direct Current Stimulation (tDCS). Ann Biomed Eng. 2020 Apr;48(4):1256-1270. doi: 10.1007/s10439-020-02447-7. Epub 2020 Jan 8.
- Background Tan M, Feng Z, Chen H, Min L, Wen H, Liu H, Hou J. Transcranial direct current stimulation regulates phenotypic transformation of microglia to relieve neuropathic pain induced by spinal cord injury. Front Behav Neurosci. 2023 Apr 4;17:1147693. doi: 10.3389/fnbeh.2023.1147693. eCollection 2023.
- Background Cavaleiro C, Martins J, Goncalves J, Castelo-Branco M. Memory and Cognition-Related Neuroplasticity Enhancement by Transcranial Direct Current Stimulation in Rodents: A Systematic Review. Neural Plast. 2020 Feb 25;2020:4795267. doi: 10.1155/2020/4795267. eCollection 2020.
- Background Nitsche MA, Paulus W. Excitability changes induced in the human motor cortex by weak transcranial direct current stimulation. J Physiol. 2000 Sep 15;527 Pt 3(Pt 3):633-9. doi: 10.1111/j.1469-7793.2000.t01-1-00633.x.
- Background Zhang Y, Cui F, Ma JH, Wang DX. Mini-dose esketamine-dexmedetomidine combination to supplement analgesia for patients after scoliosis correction surgery: a double-blind randomised trial. Br J Anaesth. 2023 Aug;131(2):385-396. doi: 10.1016/j.bja.2023.05.001. Epub 2023 Jun 9.
- Background Wen CY, Bao J, Zhou Y, Mu DL, Ding T. Combined Esketamine and Dexmedetomidine Decreases the Risk of Postoperative Delirium in Neurosurgical Pediatrics: A Randomized Controlled Trial. Drug Des Devel Ther. 2025 Sep 30;19:8865-8877. doi: 10.2147/DDDT.S550647. eCollection 2025.
- Background Lu X, Tang L, Lan H, Li C, Lin H. A Comparison of Intranasal Dexmedetomidine, Esketamine or a Dexmedetomidine-Esketamine Combination for Induction of Anaesthesia in Children: A Randomized Controlled Double-Blind Trial. Front Pharmacol. 2022 Jan 27;12:808930. doi: 10.3389/fphar.2021.808930. eCollection 2021.
- Background Junior AB Jr, Bendazzoli PS, Ferreira Melo FW Jr, Porto Franco RM, de Sousa Rocha EM, Matos Lima RD, Brondi EB. Efficacy and Safety of the Ketamine-Dexmedetomidine Combination in Adult Sedation and Anesthesia: A Systematic Review and Single-Arm Meta-Analysis of Randomized Controlled Trials. Cureus. 2025 Nov 21;17(11):e97432. doi: 10.7759/cureus.97432. eCollection 2025 Nov.
- Background Cohen SP, Bhatia A, Buvanendran A, Schwenk ES, Wasan AD, Hurley RW, Viscusi ER, Narouze S, Davis FN, Ritchie EC, Lubenow TR, Hooten WM. Consensus Guidelines on the Use of Intravenous Ketamine Infusions for Chronic Pain From the American Society of Regional Anesthesia and Pain Medicine, the American Academy of Pain Medicine, and the American Society of Anesthesiologists. Reg Anesth Pain Med. 2018 Jul;43(5):521-546. doi: 10.1097/AAP.0000000000000808.
- Background Amer M, Hylander Moller M, Alshahrani M, Shehabi Y, Arabi YM, Alshamsi F, Ingi Sigurethsson M, Rehn M, Chew MS, Kalliomaki ML, Lewis K, Al-Suwaidan FA, Al-Dorzi HM, Al-Fares A, Alsadoon N, Bell CM, Groth CM, Parke R, Mehta S, Wischmeyer PE, Al-Omari A, Olkkola KT, Alhazzani W. Ketamine Analgo-sedation for Mechanically Ventilated Critically Ill Adults: A Rapid Practice Guideline from the Saudi Critical Care Society and the Scandinavian Society of Anesthesiology and Intensive Care Medicine. Anesth Analg. 2025 Aug 1;141(2):309-326. doi: 10.1213/ANE.0000000000007173. Epub 2025 Jul 14.
- Background Su X, Chen L, Zhao Y, Li C, Liu S, Wang Z, Zhu J, Yuan X, Tian Y, Tian S. Impact of perioperative esketamine on the perioperative neurocognitive dysfunction: a systematic review and meta-analysis of randomised controlled studies. BMJ Open. 2025 May 21;15(5):e095695. doi: 10.1136/bmjopen-2024-095695.
- Background Li Y, Peng Q, Lu J, Hu L, Zhou H. Cognitive Change Associated with Anesthesia and Surgery: An Introduction to POCD for Neuroscientists. J Integr Neurosci. 2025 Jul 23;24(7):36785. doi: 10.31083/JIN36785.
- Background Zhang S, Bai C, Xu M, Li Y, Han Y, Jin Y, Zhao X. Clinical Benefits and Challenges of Esketamine in Elderly Patients During the Perioperative Period. Drug Des Devel Ther. 2025 Sep 13;19:8251-8263. doi: 10.2147/DDDT.S536813. eCollection 2025.
- Background Chen P, Qian K, Zhu K, Xiaoqing L, Dajin L. Esketamine modulates postoperative biochemical markers of oxidative stress, inflammation, and immune dysregulation in laparoscopic colorectal cancer surgery. J Med Biochem. 2025 Aug 21;44(5):1020-1027. doi: 10.5937/jomb0-56862.
- Background 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.
- Background Yao M, Fang B, Yang J, Chen P, Chen F. Esketamine combined with sufentanil versus sufentanil in patient-controlled intravenous analgesia: a meta-analysis. Front Pharmacol. 2024 Feb 7;15:1247646. doi: 10.3389/fphar.2024.1247646. eCollection 2024.
- Background Schwenk ES, Viscusi ER, Buvanendran A, Hurley RW, Wasan AD, Narouze S, Bhatia A, Davis FN, Hooten WM, Cohen SP. Consensus Guidelines on the Use of Intravenous Ketamine Infusions for Acute Pain Management From the American Society of Regional Anesthesia and Pain Medicine, the American Academy of Pain Medicine, and the American Society of Anesthesiologists. Reg Anesth Pain Med. 2018 Jul;43(5):456-466. doi: 10.1097/AAP.0000000000000806.
- Background Zhu M, Xu S, Ju X, Wang S, Yu X. Effects of the Different Doses of Esketamine on Postoperative Quality of Recovery in Patients Undergoing Modified Radical Mastectomy: A Randomized, Double-Blind, Controlled Trial. Drug Des Devel Ther. 2022 Dec 16;16:4291-4299. doi: 10.2147/DDDT.S392784. eCollection 2022.
- Background Mion G, Himmelseher S. Esketamine: Less Drowsiness, More Analgesia. Anesth Analg. 2024 Jul 1;139(1):78-91. doi: 10.1213/ANE.0000000000006851. Epub 2024 Jan 31.
- Background Trimmel H, Helbok R, Staudinger T, Jaksch W, Messerer B, Schochl H, Likar R. S(+)-ketamine : Current trends in emergency and intensive care medicine. Wien Klin Wochenschr. 2018 May;130(9-10):356-366. doi: 10.1007/s00508-017-1299-3. Epub 2018 Jan 10.
- Background Matveychuk D, Thomas RK, Swainson J, Khullar A, MacKay MA, Baker GB, Dursun SM. Ketamine as an antidepressant: overview of its mechanisms of action and potential predictive biomarkers. Ther Adv Psychopharmacol. 2020 May 11;10:2045125320916657. doi: 10.1177/2045125320916657. eCollection 2020.
- Background Wolff K, Winstock AR. Ketamine : from medicine to misuse. CNS Drugs. 2006;20(3):199-218. doi: 10.2165/00023210-200620030-00003.
- Background Sun P, Liang XQ, Chen NP, Ma JH, Zhang C, Shen YE, Zhu SN, Wang DX. Impact of mini-dose dexmedetomidine supplemented analgesia on sleep structure in patients at high risk of obstructive sleep apnea: a pilot trial. Front Neurosci. 2024 Oct 2;18:1426729. doi: 10.3389/fnins.2024.1426729. eCollection 2024.
- Background Ashraf MW, Uusalo P, Scheinin M, Saari TI. Population Modelling of Dexmedetomidine Pharmacokinetics and Haemodynamic Effects After Intravenous and Subcutaneous Administration. Clin Pharmacokinet. 2020 Nov;59(11):1467-1482. doi: 10.1007/s40262-020-00900-3.
- Background Verret M, Le JBP, Lalu MM, Jeffers MS, McIsaac DI, Nicholls SG, Turgeon AF, Ramchandani R, Li H, Hutton B, Zivkovic F, Graham M, Le M, Geist A, Berube M, O'Hearn K, Gilron I, Poulin P, Daudt H, Martel G, McVicar J, Moloo H, Fergusson DA. Effectiveness of dexmedetomidine on patient-centred outcomes in surgical patients: a systematic review and Bayesian meta-analysis. Br J Anaesth. 2024 Sep;133(3):615-627. doi: 10.1016/j.bja.2024.06.007. Epub 2024 Jul 16.
- Background Fondeur J, Escudero Mendez L, Srinivasan M, Hamouda RK, Ambedkar B, Arzoun H, Sahib I, Mohammed L. Dexmedetomidine in Prevention of Postoperative Delirium: A Systematic Review. Cureus. 2022 Jun 3;14(6):e25639. doi: 10.7759/cureus.25639. eCollection 2022 Jun.
- Background Strada AL, Tevay A, Scoggins M, Gonzalez K. Dexmedetomidine for Postoperative Delirium Prevention in the Older Adult: An Integrative Review. AANA J. 2024 Oct 1;92(5):383-389.
- Background Wang K, Wu M, Xu J, Wu C, Zhang B, Wang G, Ma D. Effects of dexmedetomidine on perioperative stress, inflammation, and immune function: systematic review and meta-analysis. Br J Anaesth. 2019 Dec;123(6):777-794. doi: 10.1016/j.bja.2019.07.027. Epub 2019 Oct 24.
- Background Li B, Li Y, Tian S, Wang H, Wu H, Zhang A, Gao C. Anti-inflammatory Effects of Perioperative Dexmedetomidine Administered as an Adjunct to General Anesthesia: A Meta-analysis. Sci Rep. 2015 Jul 21;5:12342. doi: 10.1038/srep12342.
- Background Blaudszun G, Lysakowski C, Elia N, Tramer MR. Effect of perioperative systemic alpha2 agonists on postoperative morphine consumption and pain intensity: systematic review and meta-analysis of randomized controlled trials. Anesthesiology. 2012 Jun;116(6):1312-22. doi: 10.1097/ALN.0b013e31825681cb.
- Background Wang L, Liang XQ, Sun YX, Hua Z, Wang DX. Effect of perioperative dexmedetomidine on sleep quality in adult patients after noncardiac surgery: A systematic review and meta-analysis of randomized trials. PLoS One. 2024 Dec 5;19(12):e0314814. doi: 10.1371/journal.pone.0314814. eCollection 2024.
- Background Weerink MAS, Struys MMRF, Hannivoort LN, Barends CRM, Absalom AR, Colin P. Clinical Pharmacokinetics and Pharmacodynamics of Dexmedetomidine. Clin Pharmacokinet. 2017 Aug;56(8):893-913. doi: 10.1007/s40262-017-0507-7.
- Background Dilmen OK, Meco BC, Evered LA, Radtke FM. Postoperative neurocognitive disorders: A clinical guide. J Clin Anesth. 2024 Feb;92:111320. doi: 10.1016/j.jclinane.2023.111320. Epub 2023 Nov 8.
- Background Lahiri NK, Vuckovic N, Sidhu AS, Li J, Sun Y, Naiken S, Curtis SJ, Bisch E, Bolda R, Nagra PS, Mann G, Gonzales AE, Smith L, Anderson BP, Liu Z, Adams DC, Meng L. Patterns of prevention effectiveness in postoperative neurocognitive disorder and delayed neurocognitive recovery research: a systematic review with meta-regression of randomised trials. Br J Anaesth. 2025 Aug;135(2):340-359. doi: 10.1016/j.bja.2025.04.021. Epub 2025 Jun 5.
- Background Hu Z, Zhang F, Liao Q, Ouyang W. The Glymphatic System: A Potential Pathophysiological Focus for Perioperative Neurocognitive Disorder. Explor Res Hypothesis Med. 2021;6(1):24-27. doi: 10.14218/ERHM.2020.00041.
- Background Travica N, Aslam H, O'Neil A, Lane MM, Berk M, Gamage E, Walder K, Liu ZSJ, Segasby T, Marx W. Brain derived neurotrophic factor in perioperative neurocognitive disorders: Current evidence and future directions. Neurobiol Learn Mem. 2022 Sep;193:107656. doi: 10.1016/j.nlm.2022.107656. Epub 2022 Jul 2.
- Background Cheng C, Wan H, Cong P, Huang X, Wu T, He M, Zhang Q, Xiong L, Tian L. Targeting neuroinflammation as a preventive and therapeutic approach for perioperative neurocognitive disorders. J Neuroinflammation. 2022 Dec 12;19(1):297. doi: 10.1186/s12974-022-02656-y.
- Background Maisat W, Yuki K. The Role of Damage-Associated Molecular Patterns in Perioperative Neurocognitive Disorders: A Narrative Review. Anesth Analg. 2026 Feb 1;142(2):312-325. doi: 10.1213/ANE.0000000000007682. Epub 2025 Aug 5.
- Background Yang T, Velagapudi R, Terrando N. Neuroinflammation after surgery: from mechanisms to therapeutic targets. Nat Immunol. 2020 Nov;21(11):1319-1326. doi: 10.1038/s41590-020-00812-1. Epub 2020 Oct 19.
- Background Chen L, Au E, Saripella A, Kapoor P, Yan E, Wong J, Tang-Wai DF, Gold D, Riazi S, Suen C, He D, Englesakis M, Nagappa M, Chung F. Postoperative outcomes in older surgical patients with preoperative cognitive impairment: A systematic review and meta-analysis. J Clin Anesth. 2022 Sep;80:110883. doi: 10.1016/j.jclinane.2022.110883. Epub 2022 May 24.
- Background Weiss Y, Zac L, Refaeli E, Ben-Yishai S, Zegerman A, Cohen B, Matot I. Preoperative Cognitive Impairment and Postoperative Delirium in Elderly Surgical Patients: A Retrospective Large Cohort Study (The CIPOD Study). Ann Surg. 2023 Jul 1;278(1):59-64. doi: 10.1097/SLA.0000000000005657. Epub 2022 Aug 1.
- Background Park S, Kim J, Ha Y, Kim KN, Yi S, Koo BN. Preoperative mild cognitive impairment as a risk factor of postoperative cognitive dysfunction in elderly patients undergoing spine surgery. Front Aging Neurosci. 2024 Jan 12;16:1292942. doi: 10.3389/fnagi.2024.1292942. eCollection 2024.
- Background Aldecoa C, Bettelli G, Bilotta F, Sanders RD, Aceto P, Audisio R, Cherubini A, Cunningham C, Dabrowski W, Forookhi A, Gitti N, Immonen K, Kehlet H, Koch S, Kotfis K, Latronico N, MacLullich AMJ, Mevorach L, Mueller A, Neuner B, Piva S, Radtke F, Blaser AR, Renzi S, Romagnoli S, Schubert M, Slooter AJC, Tommasino C, Vasiljewa L, Weiss B, Yuerek F, Spies CD. Update of the European Society of Anaesthesiology and Intensive Care Medicine evidence-based and consensus-based guideline on postoperative delirium in adult patients. Eur J Anaesthesiol. 2024 Feb 1;41(2):81-108. doi: 10.1097/EJA.0000000000001876. Epub 2023 Aug 30.
- Background Ren X, Huiqiao L, Wu Y, Zhang T, Chen P, Li L, Zhao G, Wang F. Perioperative neurocognitive disorders: a comprehensive review of terminology, clinical implications, and future research directions. Front Neurol. 2025 Aug 26;16:1526021. doi: 10.3389/fneur.2025.1526021. eCollection 2025.
- Background Needham MJ, Webb CE, Bryden DC. Postoperative cognitive dysfunction and dementia: what we need to know and do. Br J Anaesth. 2017 Dec 1;119(suppl_1):i115-i125. doi: 10.1093/bja/aex354.
- Background Nilsson U, Amirpour A, Lampi M, Guenna Holmgren A, Markovic G, Zecevic E, Nomm M, Drakenberg A, Claesson Lingehall H, Damen T, Martinik A, Saarijarvi M, Bergman L, Eckerblad J; PeriBrainCare. Older Patients' Postoperative Neurocognitive Recovery: A Narrative Review. Clin Interv Aging. 2025 Dec 16;20:2579-2591. doi: 10.2147/CIA.S559531. eCollection 2025.
- Background Suraarunsumrit P, Srinonprasert V, Kongmalai T, Suratewat S, Chaikledkaew U, Rattanasiri S, McKay G, Attia J, Thakkinstian A. Outcomes associated with postoperative cognitive dysfunction: a systematic review and meta-analysis. Age Ageing. 2024 Jul 2;53(7):afae160. doi: 10.1093/ageing/afae160.
- Background Mohanty S, Gillio A, Lindroth H, Ortiz D, Holler E, Azar J, Boustani M, Zarzaur B. Major Surgery and Long Term Cognitive Outcomes: The Effect of Postoperative Delirium on Dementia in the Year Following Discharge. J Surg Res. 2022 Feb;270:327-334. doi: 10.1016/j.jss.2021.08.043. Epub 2021 Oct 29.
- Background Monk TG, Weldon BC, Garvan CW, Dede DE, van der Aa MT, Heilman KM, Gravenstein JS. Predictors of cognitive dysfunction after major noncardiac surgery. Anesthesiology. 2008 Jan;108(1):18-30. doi: 10.1097/01.anes.0000296071.19434.1e.
- Background Moller JT, Cluitmans P, Rasmussen LS, Houx P, Rasmussen H, Canet J, Rabbitt P, Jolles J, Larsen K, Hanning CD, Langeron O, Johnson T, Lauven PM, Kristensen PA, Biedler A, van Beem H, Fraidakis O, Silverstein JH, Beneken JE, Gravenstein JS. Long-term postoperative cognitive dysfunction in the elderly ISPOCD1 study. ISPOCD investigators. International Study of Post-Operative Cognitive Dysfunction. Lancet. 1998 Mar 21;351(9106):857-61. doi: 10.1016/s0140-6736(97)07382-0.
- Background Alhamdah Y, Li WY, Nagappa M, Yan E, He D, Sarieplla A, Englesakis M, Elias Z, Chan MTV, Wang DX, Chung F. Perioperative approaches to prevent delayed neurocognitive recovery and postoperative neurocognitive disorder in older surgical patients: A systematic review and meta-analysis of randomized controlled trials. J Anaesthesiol Clin Pharmacol. 2025 Jan-Mar;41(1):3-14. doi: 10.4103/joacp.joacp_396_23. Epub 2024 Oct 16.
- Background Fenta E, Teshome D, Kibret S, Hunie M, Tiruneh A, Belete A, Molla A, Dessie B, Geta K. Incidence and risk factors of postoperative delirium in elderly surgical patients 2023. Sci Rep. 2025 Jan 9;15(1):1400. doi: 10.1038/s41598-024-84554-2.
- Background Vacas S, Canales C, Deiner SG, Cole DJ. Perioperative Brain Health in the Older Adult: A Patient Safety Imperative. Anesth Analg. 2022 Aug 1;135(2):316-328. doi: 10.1213/ANE.0000000000006090. Epub 2022 May 18.
- Background Thedim M, Vacas S. Postoperative Delirium and the Older Adult: Untangling the Confusion. J Neurosurg Anesthesiol. 2024 Jul 1;36(3):184-189. doi: 10.1097/ANA.0000000000000971. Epub 2024 Apr 29.
- Background Li YW, Li HJ, Li HJ, Zhao BJ, Guo XY, Feng Y, Zuo MZ, Yu YP, Kong H, Zhao Y, Huang D, Deng CM, Hu XY, Liu PF, Li Y, An HY, Zhang HY, Wang MR, Wu YF, Wang DX, Sessler DI; Peking University Clinical Research Program Study Group. Delirium in Older Patients after Combined Epidural-General Anesthesia or General Anesthesia for Major Surgery: A Randomized Trial. Anesthesiology. 2021 Aug 1;135(2):218-232. doi: 10.1097/ALN.0000000000003834.
- Background Evered L, Silbert B, Knopman DS, Scott DA, DeKosky ST, Rasmussen LS, Oh ES, Crosby G, Berger M, Eckenhoff RG; Nomenclature Consensus Working Group. Recommendations for the nomenclature of cognitive change associated with anaesthesia and surgery-2018. Br J Anaesth. 2018 Nov;121(5):1005-1012. doi: 10.1016/j.bja.2017.11.087. Epub 2018 Jun 15.
- Background Kong H, Xu LM, Wang DX. Perioperative neurocognitive disorders: A narrative review focusing on diagnosis, prevention, and treatment. CNS Neurosci Ther. 2022 Aug;28(8):1147-1167. doi: 10.1111/cns.13873. Epub 2022 Jun 1.
- Background Krause BM, Sabia S, Manning HJ, Singh-Manoux A, Sanders RD. Association between major surgical admissions and the cognitive trajectory: 19 year follow-up of Whitehall II cohort study. BMJ. 2019 Aug 7;366:l4466. doi: 10.1136/bmj.l4466.
- Background Kainz E, Juilfs N, Harler U, Kahl U, Mewes C, Zollner C, Fischer M. The impact of cognitive reserve on delayed neurocognitive recovery after major non-cardiac surgery: an exploratory substudy. Front Aging Neurosci. 2023 Nov 23;15:1267998. doi: 10.3389/fnagi.2023.1267998. eCollection 2023.
Drugs
| Evaluation | Drug | Modality | Dose | Route |
|---|---|---|---|---|
| Subject | Dexmedetomidine | Other / unclassified | 0.1 ug/kg | — |
| Subject | Esketamine | Other / unclassified | 0.05 mg/kg | — |
| Background | Sufentanil | Other / unclassified | — | — |