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Older PatientsPhase 4NCT06566469

Dexmedetomidine-esketamine Combined Nasal Administration and Emergence Delirium

A Phase 4 study testing Dexmedetomidine, Esketamine and Normal saline in people with Older Patients and Nasal Administration, run by Peking University First Hospital at 1 site in China.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

Emergence delirium is common in older patients after surgery and associated with worse perioperative outcomes, including increased postoperative delirium. Nasal administrations of both dexmedetomidine and esketamine are approved for medical purposes. Read more about this study

Who is it for?
Ages 65 years and older
What is being tested?
Dexmedetomidine, Esketamine and Normal saline
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
340 participants
Where
1 siteChina
Study dates
2 Sep 2024to 1 May 2025
Phase
Phase 4
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 65 years and older
  • All sexes
  • No healthy volunteers
  • Older adult

Who may be able to join

  • Aged ≥ 65 years;
  • Scheduled for inpatient elective or semi-elective surgery under general anesthesia, with an expected surgical duration of ≤2 hours;
  • Planned to stay in hospital for at least 1 day after surgery.

Who cannot join

  • Not suitable for intranasal drug administration due to nasal disease (e.g., rhinitis, nasal polyps, or nasal congestion due to any cause);
  • Preoperative schizophrenia, epilepsy, Parkinson's disease, myasthenia gravis, or delirium;
  • Inability to communicate due to coma, severe dementia, or language barrier before surgery;
  • Brain trauma or neurosurgery;
  • Use of sedatives or hypnotics at bedtime during the last month;
  • History of hyperthyroidism or pheochromocytoma;
Show all 10Show fewer
  • Preoperative left ventricular ejection fraction <30%, or sick sinus node syndrome, severe sinus bradycardia (heart rate <50 beats per minute), or atrioventricular block of degree II or higher without pacemaker, or systolic blood pressure <90 mmHg before enrollment;
  • Severe hepatic dysfunction (Child-Pugh class C), severe renal dysfunction (receiving dialysis before surgery), or American Society of Anesthesiologists classification ≥ IV;
  • Planned admission to the intensive care unit after surgery;
  • Allergic to dexmedetomidine and/or esketamine, or any other conditions that are considered unsuitable for study participation.

Trial locations and contacts

1 site in 1 country.

China1 site

  • Peking University First Hospital

    Beijing, Beijing Municipality, 100034

Other trials in China

About this study

Official title: Effect of Dexmedetomidine-esketamine Combined Nasal Administration on Emergence Delirium in Elderly Patients After Surgery: a Randomized, Double-blind, Placebo-controlled Trial

Emergence delirium is common in older patients after surgery and associated with worse perioperative outcomes, including increased postoperative delirium. Nasal administrations of both dexmedetomidine and esketamine are approved for medical purposes. Combination of low-dose dexmedetomidine and esketamine has shown some synergic effects in analgesia and anxiolysis. In a recent randomized trial, combined nasal administration of dexmedetomidine and esketamine was more effective in reducing pre-dental anxiety in pediatric patients. The investigators hypothesize that perioperative nasal administration of dexmedetomidine-esketamine combination can reduce the incidence of emergence delirium in older patients after surgery.

Read the detailed description

Delirium is a common brain dysfunction syndrome in older patients after major surgery. Delirium that occurs after surgery includes emergence delirium and postoperative delirium. Emergence delirium occurred in 17.5% to 37.0% of patients following general anesthesia. The reported incidence of postoperative delirium ranged from 12.0% to 32.9% in older patients after noncardiac surgery. It is well known that the occurrence of postoperative delirium is associated with adverse outcomes. Recent studies found that emergence delirium is also associated with adverse perioperative outcomes, including increased postoperative delirium, more non-delirium complications, longer hospital stay, and higher healthcare costs.

Dexmedetomidine is a highly selective alpha 2-adrenoceptor agonist with sedative, anxiolytic, and analgesic effects. Prophylactic administration of dexmedetomidine preoperatively or intraoperatively has also been shown to reduce the incidence of postoperative delirium. Dexmedetomidine via nasal administration is now widely used for pediatric preoperative sedation. Nasal administration of dexmedetomidine is also used in adults. In a retrospective study, postoperative nasal administration of dexmedetomidine (100 μg) to elderly orthopedic surgical patients improved analgesia and reduced symptoms of agitation. A recent study of patients undergoing gynecologic laparoscopic surgery, night-time dexmedetomidine (1.5 µg/kg) administration by nasal drops from preoperative day 1 to postoperative day 5 improved sleep quality and reduced the incidence of postoperative delirium.

Esketamine is a N-methyl-D-aspartic acid receptor antagonist and has been used as an anesthetic and analgesic. Low-dose intravenous infusion of ketamine is recommended for postoperative analgesia. Esketamine is s-enantiomer of ketamine and twice as potent as ketamine in analgesic potency. Nasal administration of esketamine is approved by FDA for intractable depression in adults. A randomized trial showed that nasal application of esketamine was effective in relieving post-thoracic puncture pain in adult patients without significant adverse effects. And postoperative pain is a common risk factor of emergence delirium and postoperative delirium.

This randomized trial is designed to test the hypothesis that combined nasal administration of dexmedetomidine-esketamine combination may reduce the incidence of emergence delirium in older patients after surgery.

Being tested
Dexmedetomidine, Esketamine, Normal saline
Keywords
Older patients, Nasal administration, Dexmedetomidine, Esketamine, General anesthesia, Emergence delirium
Medical subject headings
Emergence Delirium

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • DexmedetomidineDrug

    Dexmedetomidine 0.5 µg/kg is administered via nasal spray at 20:30 pm the day before surgery and at 07:30 am and 20:30 pm the day of surgery.

  • EsketamineDrug

    Esketamine 0.2 mg/kg is administered via nasal spray at 20:30 pm the day before surgery and at 07:30 am and 20:30 pm the day of surgery.

  • Normal salineDrug

    Normal saline at the same volume is administered via nasal spray at 20:30 pm the day before surgery and at 07:30 am and 20:30 pm the day of surgery.

Study groups in NCT06566469
Study groupRoleWhat they receive
Combined dexmedetomidine-esketamineExperimentalA mixture of dexmedetomidine 0.5 µg/kg and esketamine 0.2 mg/kg is administered via nasal spray at 20:30 pm the day before surgery and at 07:30 am and 20:30 pm the day of surgery.
Receives: Drug: Dexmedetomidine; Drug: Esketamine
Normal salinePlacebo comparatorPlacebo (normal saline) at the same volume is administered via nasal spray at 20:30 pm the day before surgery and at 07:30 am and 20:30 pm the day of surgery.
Receives: Drug: Normal saline

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Incidence of emergence delirium after surgery

    Emergence delirium is assessed with the Richmond Agitation Sedation Scale (RASS; scores range from -5 [unarousable] to +4 [combative] and 0 indicates alert and calm) and the Confusion Assessment Method for the Intensive Care Unit (CAM-ICU) at 5 and 30 minutes after admission to the post-anesthesia care unit.

    Measured: During stay in the post-anesthesia care unit

Secondary outcomes (3)

  1. Incidence of emergence agitation

    Emergence agitation is assessed with the RASS after surgery from cessation of general anesthesia to leaving operating room. A RASS score ≥+2 at any time is defined as having emergence agitation.

    Measured: During anesthesia emergence in the operating room

  2. Subjective sleep quality score

    Subjective sleep quality is assessed with the Richards-Campbell Sleep Questionnaire (RCSQ). The RCSQ is a self-reported measure that evaluates perception of nighttime sleep in five items, including sleep depth, sleep latency, number of awakenings, returning to sleep, and overall sleep quality. Each item is assessed with a 100 millimeter visual analog scale (score ranges from 0 to 100, with higher scores indicating better sleep quality). The mean score of the five items represents the overall sleep quality.

    Measured: The night before surgery and the night of surgery

  3. Incidence of delayed neurocognitive recovery

    Cognition is assessed with the telephone-Montreal Cognitive Assessment (T-MoCA; score ranges from 0 to 22, with higher score indicating better function). A reducation of T-MoCA score of ≥1 standard deviation (SD) from baseline is defined as having delayed neurocognitive recovery.

    Measured: At 5 days after surgery

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted22 Aug 2024
  2. Study start2 Sep 2024
  3. Primary completion28 Mar 2025
  4. Study completion1 May 2025

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 4
Primary purpose
Prevention
Allocation
Randomised
Intervention model
Parallel groups
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
340 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT06566469
Sponsor's protocol ID
2024-405
Status last verified
Jul 2025
First submitted
20 Aug 2024
Last updated
31 Jul 2025
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • Marcantonio ER. Postoperative delirium: a 76-year-old woman with delirium following surgery. JAMA. 2012 Jul 4;308(1):73-81. doi: 10.1001/jama.2012.6857.

    PubMed 22669559

  • Silverstein JH, Timberger M, Reich DL, Uysal S. Central nervous system dysfunction after noncardiac surgery and anesthesia in the elderly. Anesthesiology. 2007 Mar;106(3):622-8. doi: 10.1097/00000542-200703000-00026. No abstract available.

    PubMed 17325520

  • Aldecoa C, Bettelli G, Bilotta F, Sanders RD, Audisio R, Borozdina A, Cherubini A, Jones C, Kehlet H, MacLullich A, Radtke F, Riese F, Slooter AJ, Veyckemans F, Kramer S, Neuner B, Weiss B, Spies CD. European Society of Anaesthesiology evidence-based and consensus-based guideline on postoperative delirium. Eur J Anaesthesiol. 2017 Apr;34(4):192-214. doi: 10.1097/EJA.0000000000000594.

    PubMed 28187050

  • Card E, Pandharipande P, Tomes C, Lee C, Wood J, Nelson D, Graves A, Shintani A, Ely EW, Hughes C. Emergence from general anaesthesia and evolution of delirium signs in the post-anaesthesia care unit. Br J Anaesth. 2015 Sep;115(3):411-7. doi: 10.1093/bja/aeu442. Epub 2014 Dec 23.

    PubMed 25540068

  • Hesse S, Kreuzer M, Hight D, Gaskell A, Devari P, Singh D, Taylor NB, Whalin MK, Lee S, Sleigh JW, Garcia PS. Association of electroencephalogram trajectories during emergence from anaesthesia with delirium in the postanaesthesia care unit: an early sign of postoperative complications. Br J Anaesth. 2019 May;122(5):622-634. doi: 10.1016/j.bja.2018.09.016. Epub 2018 Oct 25.

    PubMed 30915984

  • Zhang Y, He ST, Nie B, Li XY, Wang DX. Emergence delirium is associated with increased postoperative delirium in elderly: a prospective observational study. J Anesth. 2020 Oct;34(5):675-687. doi: 10.1007/s00540-020-02805-8. Epub 2020 Jun 7.

    PubMed 32507939

  • Wu J, Gao S, Zhang S, Yu Y, Liu S, Zhang Z, Mei W. Perioperative risk factors for recovery room delirium after elective non-cardiovascular surgery under general anaesthesia. Perioper Med (Lond). 2021 Feb 3;10(1):3. doi: 10.1186/s13741-020-00174-0.

    PubMed 33531068

  • Gu WJ, Zhou JX, Ji RQ, Zhou LY, Wang CM. Incidence, risk factors, and consequences of emergence delirium after elective brain tumor resection. Surgeon. 2022 Oct;20(5):e214-e220. doi: 10.1016/j.surge.2021.09.005. Epub 2021 Nov 12.

    PubMed 34782237

  • Tesfaye Mekonin G, Kelbesa Olika M, Birhanu Wedajo M, Tolasa Badada A, Dukessa Dubiwak A, Tageza Ilala T, Gebre MN. Prevalence of Emergence Delirium and Associated Factors among Older Patients Who Underwent Elective Surgery: A Multicenter Observational Study. Anesthesiol Res Pract. 2022 Sep 9;2022:2711310. doi: 10.1155/2022/2711310. eCollection 2022.

    PubMed 36119120

  • 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.

    PubMed 30336844

  • Berian JR, Zhou L, Russell MM, Hornor MA, Cohen ME, Finlayson E, Ko CY, Rosenthal RA, Robinson TN. Postoperative Delirium as a Target for Surgical Quality Improvement. Ann Surg. 2018 Jul;268(1):93-99. doi: 10.1097/SLA.0000000000002436.

    PubMed 28742701

  • Saravana-Bawan B, Warkentin LM, Rucker D, Carr F, Churchill TA, Khadaroo RG. Incidence and predictors of postoperative delirium in the older acute care surgery population: a prospective study. Can J Surg. 2019 Feb 1;62(1):33-38. doi: 10.1503/cjs.016817.

    PubMed 30693744

  • Tawab Saljuqi A, Hanna K, Asmar S, Tang A, Zeeshan M, Gries L, Ditillo M, Kulvatunyou N, Castanon L, Joseph B. Prospective Evaluation of Delirium in Geriatric Patients Undergoing Emergency General Surgery. J Am Coll Surg. 2020 May;230(5):758-765. doi: 10.1016/j.jamcollsurg.2020.01.029. Epub 2020 Feb 21.

    PubMed 32088308

  • Silva AR, Regueira P, Albuquerque E, Baldeiras I, Cardoso AL, Santana I, Cerejeira J. Estimates of Geriatric Delirium Frequency in Noncardiac Surgeries and Its Evaluation Across the Years: A Systematic Review and Meta-analysis. J Am Med Dir Assoc. 2021 Mar;22(3):613-620.e9. doi: 10.1016/j.jamda.2020.08.017. Epub 2020 Oct 1.

    PubMed 33011097

  • Igwe EO, Nealon J, O'Shaughnessy P, Bowden A, Chang HR, Ho MH, Montayre J, Montgomery A, Rolls K, Chou KR, Chen KH, Traynor V, Smerdely P. Incidence of postoperative delirium in older adults undergoing surgical procedures: A systematic literature review and meta-analysis. Worldviews Evid Based Nurs. 2023 Jun;20(3):220-237. doi: 10.1111/wvn.12649. Epub 2023 May 2.

    PubMed 37128953

Questions about this trial

What is this clinical trial studying?

A Phase 4 study testing Dexmedetomidine, Esketamine and Normal saline in people with Older Patients and Nasal Administration, run by Peking University First Hospital at 1 site in China.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 3 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 31 Jul 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Incidence of emergence delirium after surgery (time frame: During stay in the post-anesthesia care unit). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT06566469, which also lists 58 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 31 Jul 2025.

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