Night-time Dexmedetomidine-esketamine Infusion and Sleep Quality With Mechanical Ventilation

Sponsor

Peking University First Hospital (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT05718024

Collaborator

(none)

174

Enrollment

Arms

28.9

Anticipated Duration (Months)

Study Details

Study Description

Brief Summary

Dexmedetomidine and ketamine are both suggested for sedation and analgesia in ICU patients with mechanical ventilation. 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 with mechanical ventilation in the ICU.

Condition or Disease	Intervention/Treatment	Phase
Intensive Care Unit Mechanical Ventilation Dexmedetomidine Esketamine Sleep Quality	Drug: Dexmedetomidine-esketamine Drug: Propofol-remifentanil	Phase 4

Detailed Description

Sleep disturbances are common in patients with mechanical ventilation during intensive care unit (ICU) stay. 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 with mechanical ventilation in ICU patients with mechanical ventilation and the safety of this regimen.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

174 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Triple (Participant, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

Impact of Night-time Dexmedetomidine-esketamine Infusion on Sleep Quality of Patients With Mechanical Ventilation in ICU: a Randomized Controlled Trial

Anticipated Study Start Date :

Feb 1, 2023

Anticipated Primary Completion Date :

Jun 1, 2025

Anticipated Study Completion Date :

Jul 1, 2025

Arms and Interventions

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, 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.
Active Comparator: Propofol-remifentanil Propofol and remifentanil will be infused during night-time (8 pm to 6:30 am) for ICU patients with mechanical ventilation, for a duration of up to 5 days.	Drug: Propofol-remifentanil Propofol and remifentanil will be infused during night-time (8 pm to 6:30 am) for ICU patients with mechanical ventilation.

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, 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.

Active Comparator: Propofol-remifentanil

Propofol and remifentanil will be infused during night-time (8 pm to 6:30 am) for ICU patients with mechanical ventilation, for a duration of up to 5 days.

Drug: Propofol-remifentanil

Propofol and remifentanil will be infused during night-time (8 pm to 6:30 am) for ICU patients with mechanical ventilation.

Outcome Measures

Primary Outcome Measures

Percentage of non-rapid eye movement sleep stage 2 [From 21:00 pm to next 6:00 am during the first night after recruitment]
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.

Secondary Outcome Measures

Total sleep time [From 21:00 pm to next 6:00 am during the first night after enrollment]
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.
Sleep efficiency [From 21:00 pm to next 6:00 am during the first night after enrollment]
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.
Sleep fragmentation index [From 21:00 pm to next 6:00 am during the first night after enrollment]
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.
Time of sleep in each stage [From 21:00 pm to next 6:00 am during the first night after enrollment]
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.
Percentage of sleep in each stage (except percentage of non-rapid eye movement sleep stage 2) [From 21:00 pm to next 6:00 am during the first night after enrollment]
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.
Pain intensity [During the first 5 days after enrollment]
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.
Subjective sleep quality [During the first 5 days after enrollment]
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.
Sedation-agitation level [During the first 5 days after enrollment]
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.
Delirium occurrence [During the first 5 days after enrollment]
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.
Duration of mechanical ventilation [Up to 30 days after enrollment]
Mechanical ventilation during ICU stay.
Length of ICU stay [Up to 30 days after enrollment]
Length of ICU stay.

Other Outcome Measures

Length of hospital stay [Up to 30 days after enrollment]
Length of hospital stay.
Incidence of complications within 30 days [Up to 30 days after enrollment]
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.
All-cause mortality within 30 days [Up to 30 days after enrollment]
All-cause mortality within 30 days
Subjective sleep quality at 30 days [At 30 days after enrollment]
Subjective sleep quality is assessed with the Richards-Campbell Sleep Questionnaire (RCSQ). The RCSQ is a self-reported measure that evaluated perception of nighttime sleep in five items, including sleep depth, sleep latency, number of awakenings, returning to sleep, and overall sleep quality. Each item was assessed with a 100-millimeter visual analog scale (VAS; score ranges from 0 to 100, with higher scores representing better sleep). The mean score of the five items represents the overall RCSQ score.
Quality of life at 30 days in physical domain [At 30 days after enrollment]
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).
Quality of life at 30 days in psychological domain [At 30 days after enrollment]
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).
Quality of life at 30 days in social relationship domain [At 30 days after enrollment]
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).
Quality of life at 30 days in environmental domain [At 30 days after enrollment]
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).

Eligibility Criteria

Criteria

Ages Eligible for Study:

50 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Aged 50 years or older;
Receiving invasive mechanical ventilation or non-invasive auxiliary ventilation in the ICU, with an estimated duration of ≥24 hours;
Sedation is necessary as judged by the intensivists.

Exclusion Criteria:

Duration of invasive/non-invasive ventilation ≥12 hours before enrollment;
Plan 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 invasive/non-invasive ventilation;
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 past 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.