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Older PatientsPhase 4NCT07151716

Sedation With Dexmedetomidine-esketamine Combination and Delirium in ICU Patients

A Phase 4 study testing Dexmedetomidine and Dexmedetomidine-esketamine combination in people with Older Patients and Postoperative Care, 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

Patients in the intensive care unit (ICU) often develop anxiety and agitation, sleep disturbances, and delirium. Delirium occurrence is associated with worse early and long-term outcomes. Read more about this study

Who is it for?
Ages 60 years and older
What is being tested?
Dexmedetomidine and Dexmedetomidine-esketamine combination
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
100 participants
Where
1 siteChina
Study dates
21 Oct 2025to 24 Apr 2026
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 60 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Aged 60 years or older;
  • Admitted to the intensive care unit (ICU) after surgery;
  • Expected to stay in the ICU for at least one night.

Who cannot join

  • History of schizophrenia, epilepsy, Parkinson's disease, or myasthenia gravis;
  • Presence of preoperative delirium, or inability to communicate due to coma, severe dementia, or language barrier;
  • Previously diagnosed obstructive sleep apnea, judged to be at high risk of moderate-to-severe obstructive sleep apnea according to the STOP-Bang questionnaire, or have a body mass index >30 kg/m²;
  • Preoperative left ventricular ejection fraction <30%, sick sinus syndrome, severe sinus bradycardia (heart rate <50 bpm), second-degree or higher atrioventricular block without a pacemaker, or systolic blood pressure <90 mmHg despite use of vasopressors;
  • Comorbid with hyperthyroidism or pheochromocytoma;
  • Severe liver dysfunction (Child-Pugh Class C), severe renal dysfunction (requiring dialysis), or expected survival ≤24 hours;
Show all 9Show fewer
  • After traumatic brain injury or neurosurgery;
  • Allergy to dexmedetomidine and/or esketamine;
  • 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 Sedation With Dexmedetomidine-esketamine Combination on Delirium in Postoperative ICU Patients: a Randomized Controlled Pilot Trial

Patients in the intensive care unit (ICU) often develop anxiety and agitation, sleep disturbances, and delirium. Delirium occurrence is associated with worse early and long-term outcomes. Dexmedetomidine and ketamine are recommended for sedation and analgesia in postoperative ICU patients, but each may induce side effects. The sedative effects of dexmedetomidine can help mitigate the neuropsychiatric side effects of esketamine. Recent studies showed that dexmedetomidine-esketamine combination improved analgesia and sleep quality without increasing side effects. This trial is designed to test the hypothesis that dexmedetomidine-esketamine combination for sedation and analgesia in postoperative ICU patients may reduce delirium.

Read the detailed description

An estimated 300 million surgical procedures are performed globally each year. Patients who have complex conditions and an elevated risk of postoperative complications frequently require admission to the intensive care unit (ICU). Among these, a subset are admitted to ICU with an endotracheal tube and continue to receive mechanical ventilation. Sleep disturbances are highly prevalent in ICU patients due to environmental factors, underlying diseases, therapeutic interventions, and pain-related stimuli.

Mechanical ventilation, painful stimulation, and sleep disturbances are important risk factors of delirium in ICU patients. Delirium is an acutely occurred brain dysfunction symdrome characteristized with fluctuating disturbances in attention, cognition, and consciousness, and is reported to occur in up to 80% of ICU patients with mechanical ventilation. Delirium occurrence is associated with worse outcomes, including prolonged mechanical ventilation, extended ICU and hospital stays, increased healthcare burden and costs, and elevated mortality risk, as well as long-term sequelae including cognitive decline, reduced quality of life, and decreased survival.

Dexmedetomidine is a highly selective α2-adrenergic receptor agonist with sedative, analgesic, and anxiolytic effects. It exerts effects by activating the endogenous sleep-promoting pathways, inducing a state like non-rapid eye movement sleep. Ketamine is a non-competitive N-methyl-D-aspartate (NMDA) receptor antagonist. Esketamine, a more potent enantiomer of ketamine, has a higher affinity for the NMDA receptor and is approximately twice as potent as ketamine. Both dexmedetomidine and ketamine are recommended for sedation and analgesia in postoperative ICU patients. However, sedative dose dexmedetomidine is associated with bradycardia and hypotension. Even low-dose esketamine can induce neuropsychiatric side effects such as dissociation, hallucinations, and nightmares.

The sedative effects of dexmedetomidine can help mitigate the neuropsychiatric side effects of esketamine. Recent studies showed that low-dose dexmedetomidine-esketamine combination improved analgesia and sleep quality without increasing side effects. It is hypothesized that dexmedetomidine-esketamine combination for sedation and analgesia in postoperative ICU patients may reduce delirium.

Being tested
Dexmedetomidine, Dexmedetomidine-esketamine combination
Keywords
Older patients, Postoperative care, Intensive Care Unit, Dexmedetomidine, Esketamine, Delirium
Medical subject headings
Delirium

What participants receive

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

  • DexmedetomidineDrug

    Also called Sedation with dexmedetomidine

    For patients with endotracheal intubation, nighttime (20:00-06:00) sedation is initiated with 0.2 μg/kg/h dexmedetomidine and increased/decreased by 0.1 μg/kg/h dexmedetomidine every 15 min, until the Richmond Agitation-Sedation Scale (RASS) reaches -2 to -1, maximal infusion rate reaches 0.7 μg/kg/h dexmedetomidine, or adverse reactions occur. Daytime (06:00-20:00) sedation is provided as above when considered necessary, with a target RASS score of -2 to +1.

    For patients without endotracheal intubation, nighttime (20:00-06:00) sedation is initiated with 0.10 μg/kg/h dexmedetomidine and increased/decreased by 0.05 μg/kg/h dexmedetomidine every 15 min, until the RASS reaches -1, maximal infusion rate reaches 0.2 μg/kg/h dexmedetomidine, or adverse reactions occur. Daytime (06:00-20:00) sedation is typically not provided.

  • Dexmedetomidine-esketamine combinationDrug

    Also called Sedation with dexmedetomidine-esketamine combination

    For patients with endotracheal intubation, nighttime (20:00-06:00) sedation is initiated with 0.1 μg/kg/h dexmedetomidine and 0.05 mg/kg/h esketamine, increased/decreased by 0.05 μg/kg/h dexmedetomidine and 0.025 mg/kg/h esketamine every 15 min, until the RASS reaches -2 to -1, maximal infusion rate reaches 0.35 μg/kg/h dexmedetomidine and 0.175 mg/kg/h esketamine, or adverse reactions occur. Daytime (06:00-20:00) sedation is provided as above when considered necessary, with a target RASS score of -2 to +1.

    For patients without endotracheal intubation, nighttime (20:00-06:00) sedation is initiated with 0.05 μg/kg/h dexmedetomidine and 0.025 mg/kg/h esketamine, and increased/decreased by 0.025 μg/kg/h dexmedetomidine and 0.0125 mg/kg/h esketamine every 15 min, until the RASS reaches -1, maximal infusion rate reaches 0.1 μg/kg/h dexmedetomidine and 0.05 mg/kg/h esketamine, or adverse reactions occur. Daytime (06:00-20:00) sedation is typically not provided.

Study groups in NCT07151716
Study groupRoleWhat they receive
DexmedetomidineActive comparatorSedation is provided with dexmedetomidine (4 μg/ml dexmedetomidine) for up to 7 days or until discharge from the ICU.
Receives: Drug: Dexmedetomidine
Dexmedetomidine-esketamine combinationExperimentalSedation is provided with dexmedetomidine-esketamine combination (2 μg/ml dexmedetomidine and 1 mg/ml esketamine) combination for up to 7 days or until discharge from the ICU.
Receives: Drug: Dexmedetomidine-esketamine combination

What is being measured

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

  1. Incidence of delirium within 7 days

    Delirium will be assessed twice daily (8:00-10:00, 18:00-20:00) for 7 days or until hospital discharge. Patients with endotracheal intubation will be assessed with the Confusion Assessment Method for the Intensive Care Unit (CAM-ICU). Patients without endotracheal intubation will be assessed with the 3-Minute Diagnostic Assessment for Delirium using the Confusion Assessment Method (3D-CAM). Positive result of delirium assessments at any timepoint is defined as occurrence of delirium.

    Measured: Up to 7 days after surgery

Secondary outcomes (4)

  1. Total sleep time (TST) on the first postoperative night

    Total sleep time will be monitored using an actigraphy device.

    Measured: From 20:00 on the night of surgery to 06:00 the next morning

  2. Postoperative pain score within 7 days

    Pain intensity will be assessed twice daily (8:00-10:00, 18:00-20:00) for 7 days or until hospital discharge, using the 11-point Numeric Rating Scale (NRS; 0 = no pain, 10 = worst pain) or the Behavioral Pain Scale (BPS; range 4-16, with higher scores indicating more severe pain; for patients with deep sedation).

    Measured: Up to 7 days after surgery

  3. Postoperative subjective sleep quality within 7 days

    Subjective sleep quality will be assessed once daily (08:00-10:00) for 7 days or until hospital discharge, using an 11-point Numeric Rating Scale (0 = best sleep, 10 = worst sleep)

    Measured: Up to 7 days after surgery

  4. Length of stay in the ICU

    Length of stay in the ICU

    Measured: Up to 30 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 posted3 Sep 2025
  2. Study start21 Oct 2025
  3. Primary completion31 Mar 2026
  4. Study completion24 Apr 2026

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
100 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT07151716
Sponsor's protocol ID
2025R069
Status last verified
Jun 2026
First submitted
25 Aug 2025
Last updated
30 Jun 2026
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • Wang S, Yu X, Cheng L, Ren W, Wen G, Wu X, Lou H, Ren X, Lu L, Hermenean A, Yao J, Li B, Lu Y, Wu X. Dexmedetomidine improves the circulatory dysfunction of the glymphatic system induced by sevoflurane through the PI3K/AKT/DeltaFosB/AQP4 pathway in young mice. Cell Death Dis. 2024 Jun 25;15(6):448. doi: 10.1038/s41419-024-06845-w.

    PubMed 38918408

  • Dong R, Liu W, Han Y, Wang Z, Jiang L, Wang L, Gu X. Influencing factors of glymphatic system during perioperative period. Front Neurosci. 2024 Sep 12;18:1428085. doi: 10.3389/fnins.2024.1428085. eCollection 2024.

    PubMed 39328423

  • Lewis K, Balas MC, Stollings JL, McNett M, Girard TD, Chanques G, Kho ME, Pandharipande PP, Weinhouse GL, Brummel NE, Chlan LL, Cordoza M, Duby JJ, Gelinas C, Hall-Melnychuk EL, Krupp A, Louzon PR, Tate JA, Young B, Jennings R, Hines A, Ross C, Carayannopoulos KL, Aldrich JM. A Focused Update to the Clinical Practice Guidelines for the Prevention and Management of Pain, Anxiety, Agitation/Sedation, Delirium, Immobility, and Sleep Disruption in Adult Patients in the ICU. Crit Care Med. 2025 Mar 1;53(3):e711-e727. doi: 10.1097/CCM.0000000000006574. Epub 2025 Feb 21.

    PubMed 39982143

  • Alexopoulou C, Kondili E, Diamantaki E, Psarologakis C, Kokkini S, Bolaki M, Georgopoulos D. Effects of dexmedetomidine on sleep quality in critically ill patients: a pilot study. Anesthesiology. 2014 Oct;121(4):801-7. doi: 10.1097/ALN.0000000000000361.

    PubMed 24988068

  • Nelson LE, Lu J, Guo T, Saper CB, Franks NP, Maze M. The alpha2-adrenoceptor agonist dexmedetomidine converges on an endogenous sleep-promoting pathway to exert its sedative effects. Anesthesiology. 2003 Feb;98(2):428-36. doi: 10.1097/00000542-200302000-00024.

    PubMed 12552203

  • 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.

    PubMed 28105598

  • Kanji S, Mera A, Hutton B, Burry L, Rosenberg E, MacDonald E, Luks V. Pharmacological interventions to improve sleep in hospitalised adults: a systematic review. BMJ Open. 2016 Jul 29;6(7):e012108. doi: 10.1136/bmjopen-2016-012108.

    PubMed 27473952

  • Weinhouse GL, Watson PL. Sedation and sleep disturbances in the ICU. Crit Care Clin. 2009 Jul;25(3):539-49, ix. doi: 10.1016/j.ccc.2009.04.003.

    PubMed 19576529

  • Trompeo AC, Vidi Y, Locane MD, Braghiroli A, Mascia L, Bosma K, Ranieri VM. Sleep disturbances in the critically ill patients: role of delirium and sedative agents. Minerva Anestesiol. 2011 Jun;77(6):604-12.

    PubMed 21617624

  • Mehta S, Cook D, Devlin JW, Skrobik Y, Meade M, Fergusson D, Herridge M, Steinberg M, Granton J, Ferguson N, Tanios M, Dodek P, Fowler R, Burns K, Jacka M, Olafson K, Mallick R, Reynolds S, Keenan S, Burry L; SLEAP Investigators; Canadian Critical Care Trials Group. Prevalence, risk factors, and outcomes of delirium in mechanically ventilated adults. Crit Care Med. 2015 Mar;43(3):557-66. doi: 10.1097/CCM.0000000000000727.

    PubMed 25493968

  • Ely EW, Inouye SK, Bernard GR, Gordon S, Francis J, May L, Truman B, Speroff T, Gautam S, Margolin R, Hart RP, Dittus R. Delirium in mechanically ventilated patients: validity and reliability of the confusion assessment method for the intensive care unit (CAM-ICU). JAMA. 2001 Dec 5;286(21):2703-10. doi: 10.1001/jama.286.21.2703.

    PubMed 11730446

  • Krewulak KD, Stelfox HT, Leigh JP, Ely EW, Fiest KM. Incidence and Prevalence of Delirium Subtypes in an Adult ICU: A Systematic Review and Meta-Analysis. Crit Care Med. 2018 Dec;46(12):2029-2035. doi: 10.1097/CCM.0000000000003402.

    PubMed 30234569

  • Mattimore D, Fischl A, Christophides A, Cuenca J, Davidson S, Jin Z, Bergese S. Delirium after Cardiac Surgery-A Narrative Review. Brain Sci. 2023 Dec 7;13(12):1682. doi: 10.3390/brainsci13121682.

    PubMed 38137130

  • 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

  • Wilson JE, Mart MF, Cunningham C, Shehabi Y, Girard TD, MacLullich AMJ, Slooter AJC, Ely EW. Delirium. Nat Rev Dis Primers. 2020 Nov 12;6(1):90. doi: 10.1038/s41572-020-00223-4.

    PubMed 33184265

Questions about this trial

What is this clinical trial studying?

A Phase 4 study testing Dexmedetomidine and Dexmedetomidine-esketamine combination in people with Older Patients and Postoperative Care, 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 9 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 30 Jun 2026. 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. 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 delirium within 7 days (time frame: Up to 7 days after surgery). 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 NCT07151716, which also lists 30 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 30 Jun 2026.

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