Dexmedetomidine, Esketamine, Intensive Care Unit, Mechanical Ventilation, Sleep Quality
Conditions
Keywords
Intensive care unit, Mechanical ventilation, Dexmedetomidine, Esketamine, Sleep quality
Brief summary
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.
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.
Interventions
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.
DRUGRoutine 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).
Sponsors
Peking University First Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
50 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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. |
| 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. |
Other
| Measure | Time frame | Description |
|---|---|---|
| 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). |
| 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 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. |
Countries
China
Outcome results
None listed