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

Phase 4
Recruiting
Conditions
Intensive Care Unit
Mechanical Ventilation
Dexmedetomidine
Esketamine
Sleep Quality
Interventions
Drug: Dexmedetomidine-esketamine
Drug: Propofol-remifentanil
Registration Number
NCT05718024
Lead Sponsor
Peking University First Hospital
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.

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.

Recruitment & Eligibility

Status
RECRUITING
Sex
All
Target Recruitment
174
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.

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Dexmedetomidine-esketamineDexmedetomidine-esketamineDexmedetomidine-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.
Propofol-remifentanilPropofol-remifentanilPropofol 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.
Primary Outcome Measures
NameTimeMethod
Percentage of non-rapid eye movement sleep stage 2From 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
NameTimeMethod
Sleep efficiencyFrom 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.

Sedation-agitation levelDuring 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.

Total sleep timeFrom 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 fragmentation indexFrom 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 stageFrom 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 intensityDuring 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 qualityDuring 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.

Delirium occurrenceDuring 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 ventilationUp to 30 days after enrollment

Mechanical ventilation during ICU stay.

Length of ICU stayUp to 30 days after enrollment

Length of ICU stay.

Trial Locations

Locations (1)

Peking University First Hospital

🇨🇳

Beijing, Beijing, China

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