Night-time Dexmedetomidine-esketamine Infusion and Sleep Quality in ICU Patients

Impact of Night-time Dexmedetomidine-esketamine Infusion on Sleep Quality of Patients With Mechanical Ventilation or High-flow Nasal Cannula Oxygen Therapy in ICU: a Randomized Controlled Trial

Dexmedetomidine and ketamine are both suggested for sedation and analgesia in ICU patients. Recent studies suggest that low-dose dexmedetomidine or ketamine/esketamine may improve sleep quality of ICU patients. The purpose of this trial is to observe whether night-time infusion of low-dose dexmedetomidine-esketamine combination can improve sleep structure of patients receiving mechanical ventilation or high-flow nasal cannula oxygen therapy in the ICU.

Study Overview

• Status: Completed
• Conditions: Sleep Quality; Dexmedetomidine; Intensive Care Unit; Mechanical Ventilation; Esketamine
• Intervention / Treatment: Drug: Dexmedetomidine-esketamine; Drug: Routine sedation and analgesia

Detailed Description

Sleep disturbances are common in patients during intensive care unit (ICU) stay, especially those receiving mechanical ventilation. Persistent sleep disturbances are associated with negative outcomes, including increased sensitivity to pain, increased risk of delirium and cardiovascular events, and delayed weaning from mechanical ventilation.

Dexmedetomidine and ketamine are both suggested for sedation and analgesia in ICU patients. Previous studies showed that night-time dexmedetomidine infusion may improve sleep quality in ICU patients with mechanical ventilation, the effect is dose-dependent. However, sedative dose dexmedetomidine increases adverse events inculding bradycardia and hypotension. Recent studies suggest that ketamine/esketamine may also improve sleep quality. But even low-dose ketamine/esketamine increases adverse events including psychiatric and dissociative symptoms. We suppose that combined use of low-dose dexmedetomidine and esketamine may produce synergic effects in improving sleep quality in ICU patients with less adverse events.

The purpose of this trial is to observe whether night-time infusion of low-dose dexmedetomidine-esketamine combination can improve sleep structure of patients receiving mechanical ventilation or high-flow nasal cannula oxygen therapy in ICU patients and the safety of this regimen.

• Study Type: Interventional
• Enrollment (Actual): 174
• Phase: Phase 4

Contacts and Locations

Study Locations

• China
  • Beijing Municipality
    • Beijing, Beijing Municipality, China, 100034
      • Peking University First Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 50 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Aged 50 years or older;
• Admitted to the intensive care unit (ICU) after surgery;
• Receiving mechanical ventilation or high-flow nasal cannula oxygen therapy during night-time (after 6 pm), with an expected duration of ≥12 hours.

Exclusion Criteria:

• Duration of invasive/non-invasive ventilation ≥12 hours before enrollment;
• Planning to receive muscle relaxant treatment;
• History of schizophrenia, epilepsy, Parkinson's disease, or myasthenia gravis;
• Unable to communicate due to coma, delirium, severe dementia, or language barrier before receiving mechanical ventilation or high-flow nasal cannula oxygen therapy;
• Acute stroke or hypoxic encephalopathy, or after craniocerebral injury or neurosurgery;
• Comorbid with hyperthyroidism or pheochromocytoma;
• Taking sedative/hypnotic drugs or analgesics regularly (for more than 1 week) in the last month;
• LVEF<30%; sick sinus syndrome, severe sinus bradycardia (heart rate<50 beats/min), atrioventricular block of more than II degree and without pacemaker; or systolic blood pressure <90 mmHg despite vasopressor infusion;
• Severe liver dysfunction (Child-Pugh C grade), severe renal dysfunction (dialysis), or estimated survival ≤24 hours;
• Diagnosed obstructive sleep apnea, or body mass index >30 kg/m2;
• Allergies to dexmedetomidine and/or esketamine, or other conditions that are considered unsuitable for study participation;
• Enrolled in other clinical studies.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Dexmedetomidine-esketamine; Dexmedetomidine-esketamine combination will be infused during night-time (8 pm to 6:30 am) for ICU patients with mechanical ventilation or high-flow nasal cannula oxygen therapy, for a duration of up to 5 days.	Drug: Dexmedetomidine-esketamine; Dexmedetomidine-esketamine combination will be infused during night-time (8 pm to 6:30 am) for ICU patients with mechanical ventilation or high-flow nasal cannula oxygen therapy.
Active Comparator: Control; Propofol and remifentanil will be infused during night-time (8 pm to 6:30 am) for ICU patients with mechanical ventilation or high-flow nasal cannula oxygen therapy (if necessary), for a duration of up to 5 days.	Drug: Routine sedation and analgesia; Propofol and remifentanil will be infused during night-time (8 pm to 6:30 am) for ICU patients with mechanical ventilation or high-flow nasal cannula oxygen therapy (if necessary).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of non-rapid eye movement sleep stage 2	Polysomnographic monitoring is performed during the first night after recruitment with an EEG/PSG Recording System (SOMNO screen plus, SOMNO medics GmbH, Randersacker, Germany). The monitored sleep architecture is divided into wakefulness, non-rapid eye movement (stages N1, N2, and N3) sleep, and rapid eye movement (REM) sleep. The percentages of each sleep stage are calculated as the durations of each sleep stage divided by the total sleep time.	From 21:00 pm to next 6:00 am during the first night after recruitment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Total sleep time	Polysomnographic monitoring is performed during the first night after recruitment with an EEG/PSG Recording System (SOMNO screen plus, SOMNO medics GmbH, Randersacker, Germany). Total sleep time is defined as the summary of time spent in any sleep stage during the monitoring period.	From 21:00 pm to next 6:00 am during the first night after enrollment
Sleep efficiency	Polysomnographic monitoring is performed during the first night after recruitment with an EEG/PSG Recording System (SOMNO screen plus, SOMNO medics GmbH, Randersacker, Germany). Sleep efficiency is calculated as the summary of time spent in each sleep stage divided by total sleep monitoring time.	From 21:00 pm to next 6:00 am during the first night after enrollment
Sleep fragmentation index	Polysomnographic monitoring is performed during the first night after recruitment with an EEG/PSG Recording System (SOMNO screen plus, SOMNO medics GmbH, Randersacker, Germany). Sleep fragmentation index is calculated as the total number of awakenings and sleep-stage shifts divided by total sleep time.	From 21:00 pm to next 6:00 am during the first night after enrollment
Time of sleep in each stage	Polysomnographic monitoring is performed during the first night after recruitment with an EEG/PSG Recording System (SOMNO screen plus, SOMNO medics GmbH, Randersacker, Germany). The monitored sleep architecture is divided into wakefulness, non-rapid eye movement (stages N1, N2, and N3) sleep, and rapid eye movement (REM) sleep.	From 21:00 pm to next 6:00 am during the first night after enrollment
Percentage of sleep in each stage (except percentage of non-rapid eye movement sleep stage 2)	Polysomnographic monitoring is performed during the first night after recruitment with an EEG/PSG Recording System (SOMNO screen plus, SOMNO medics GmbH, Randersacker, Germany). The monitored sleep architecture is divided into wakefulness, non-rapid eye movement (stages N1, N2, and N3) sleep, and rapid eye movement (REM) sleep. The percentages of each sleep stage are calculated as the durations of each sleep stage divided by the total sleep time.	From 21:00 pm to next 6:00 am during the first night after enrollment
Pain intensity	Pain intensity is assessed twice daily (8:00 am to 10:00 am and 6:00 pm to 8:00 pm) with the numeric rating scale where 0=no pain and 10=the worst pain.	During the first 5 days after enrollment
Subjective sleep quality	Subjective sleep quality is assessed daily (8:00 am to 10:00 am) with the numeric rating scale where 0=the best sleep and 10=the worst sleep.	During the first 5 days after enrollment
Sedation-agitation level	Sedation-agitation level is assessed twice daily (8:00 am to 10:00 am and 6:00 pm to 8:00 pm) with the Richmond Agitation Sedation Scale; score ranges from -5 (unarousable) to +4 (combative) and 0 indicates alert and calm.	During the first 5 days after enrollment
Delirium occurrence	Delirium is assessed twice daily (8:00 am to 10:00 am and 6:00 pm to 8:00 pm) with the Confusion Assessment Method for the ICU.	During the first 5 days after enrollment
Duration of mechanical ventilation	Mechanical ventilation during ICU stay.	Up to 30 days after enrollment
Length of ICU stay	Length of ICU stay.	Up to 30 days after enrollment

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Length of hospital stay	Length of hospital stay.	Up to 30 days after enrollment
Incidence of complications within 30 days	Complications are defined as new-onset medical conditions other than delirium that were deemed harmful and required therapeutic intervention, i.e., grade II or higher on the Clavien-Dindo classification.	Up to 30 days after enrollment
All-cause mortality within 30 days	All-cause mortality within 30 days	Up to 30 days after enrollment
Quality of life at 30 days in physical domain	Quality of life is assessed with the World Health Organization Quality of Life-brief version (WHOQOL-BREF; a 24-item questionnaire that provides assessments of the quality of life in physical, psychological, and social relationship, and environmental domains. For each domain, the score ranges from 0 to 100, with higher score indicating better function).	At 30 days after enrollment
Quality of life at 30 days in psychological domain	Quality of life is assessed with the World Health Organization Quality of Life-brief version (WHOQOL-BREF; a 24-item questionnaire that provides assessments of the quality of life in physical, psychological, and social relationship, and environmental domains. For each domain, the score ranges from 0 to 100, with higher score indicating better function).	At 30 days after enrollment
Quality of life at 30 days in social relationship domain	Quality of life is assessed with the World Health Organization Quality of Life-brief version (WHOQOL-BREF; a 24-item questionnaire that provides assessments of the quality of life in physical, psychological, and social relationship, and environmental domains. For each domain, the score ranges from 0 to 100, with higher score indicating better function).	At 30 days after enrollment
Quality of life at 30 days in environmental domain	Quality of life is assessed with the World Health Organization Quality of Life-brief version (WHOQOL-BREF; a 24-item questionnaire that provides assessments of the quality of life in physical, psychological, and social relationship, and environmental domains. For each domain, the score ranges from 0 to 100, with higher score indicating better function).	At 30 days after enrollment
Subjective sleep quality at 30 days	Subjective sleep quality is assessed with the Pittsburgh sleep quality index (PSQI). The PSQI consists of 19 self-rated and 5 other-rated items used to assess sleep quality over a month.	At 30 days after enrollment

Collaborators and Investigators

• Sponsor: Peking University First Hospital
• Investigators: Principal Investigator: Dong-Xin Wang, MD, PhD, Peking University First Hospital

Publications and helpful links

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Study record dates

Study Major Dates

• Study Start (Actual): November 1, 2023
• Primary Completion (Actual): April 22, 2025
• Study Completion (Actual): May 23, 2025

Study Registration Dates

• First Submitted: January 29, 2023
• First Submitted That Met QC Criteria: February 6, 2023
• First Posted (Actual): February 8, 2023

Study Record Updates

• Last Update Posted (Actual): December 5, 2025
• Last Update Submitted That Met QC Criteria: December 1, 2025
• Last Verified: December 1, 2025

More Information

Terms related to this study

• Keywords: Intensive care unit; Dexmedetomidine; Sleep quality; Esketamine; Mechanical ventilation
• Additional Relevant MeSH Terms: Nervous System Diseases; Mental Disorders; Sleep Wake Disorders; Sleep Disorders, Intrinsic; Dyssomnias; Sleep Initiation and Maintenance Disorders; Anesthesia and Analgesia; Analgesia
• Other Study ID Numbers: 2023-006

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No