Dexmedetomidine-esketamine Combined Nasal Administration and Emergence Delirium

NCT06566469 | Completed Phase 4 DMC

• 1 other identifier: 2024-405
• Study Type: interventional
• Target: 340
• Locations: 1 country
• Sites: 1

Brief 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. 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.

Conditions

Older Patients; Nasal Administration; Dexmedetomidine; Esketamine; General Anesthesia; Emergence Delirium

Keywords

Older patients; Nasal administration; Dexmedetomidine; Esketamine; General anesthesia; Emergence delirium

Outcome Measures

Primary Outcomes (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.

  During stay in the post-anesthesia care unit

Secondary Outcomes (3)

• Incidence of emergence agitation

  During anesthesia emergence in the operating room

• Subjective sleep quality score

  The night before surgery and the night of surgery

• Incidence of delayed neurocognitive recovery

  At 5 days after surgery

Other Outcomes (6)

• Pain intensity within 24 hours after surgery

  Up to 24 hours after surgery

• Analgesic use within 24 hours after surgery

  Up to 24 hours after surgery

• Incidence of postoperative delirium within 3 days after surgery

  Up to 3 days after surgery

Study Arms (2)

Combined dexmedetomidine-esketamine

EXPERIMENTAL

A 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.

Drug: Dexmedetomidine; Drug: Esketamine

Normal saline

PLACEBO COMPARATOR

Placebo (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.

Drug: Normal saline

Interventions

Dexmedetomidine DRUG

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.

Combined dexmedetomidine-esketamine

Esketamine DRUG

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.

Combined dexmedetomidine-esketamine

Normal saline DRUG

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.

Normal saline

Eligibility Criteria

• Age: 65 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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;
• 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.

Sponsors & Collaborators

• Peking University First Hospital: lead

Study Sites (1)

Peking University First Hospital

Beijing, Beijing Municipality, 100034, China

Location

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MeSH Terms

Conditions

Emergence Delirium

Interventions

Dexmedetomidine; Esketamine; Saline Solution

Condition Hierarchy (Ancestors)

Delirium; Confusion; Neurobehavioral Manifestations; Neurologic Manifestations; Nervous System Diseases; Postoperative Complications; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Signs and Symptoms; Neurocognitive Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Crystalloid Solutions; Isotonic Solutions; Solutions; Pharmaceutical Preparations

Study Officials

• Dong-Xin Wang, MD, PhD

  Peking University First Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor and chairman, Department of Anesthesiology

Study Record Dates

• First Submitted: August 20, 2024
• First Posted: August 22, 2024
• Study Start: September 2, 2024
• Primary Completion: March 28, 2025
• Study Completion: May 1, 2025
• Last Updated: July 31, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)