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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

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

Conditions
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Intensive Care Unit, Mechanical Ventilation, Dexmedetomidine, Esketamine, Sleep Quality

Intervention / Treatment
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* Drug: Dexmedetomidine-esketamine
* Drug: Propofol-remifentanil


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 50 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Dexmedetomidine-esketamine<br>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<br>* Dexmedetomidine-esketamine combination will be infused during night-time (8 pm to 6:30 am) for ICU patients with mechanical ventilation.<br>|
| Active Comparator: Propofol-remifentanil<br>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<br>* Propofol and remifentanil will be infused during night-time (8 pm to 6:30 am) for ICU patients with mechanical ventilation.<br>|

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Intensive care unit, Mechanical ventilation, Dexmedetomidine, Esketamine, Sleep quality