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

Mechanical Ventilation Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05718024
• Other study ID #: 2023-006
• Status: Recruiting
• Phase: Phase 4
• Start date: November 1, 2023
• Est. completion date: July 2025

Study information

• Verified date: February 2024
• Source: Peking University First Hospital
• Contact: Dong-Xin Wang, MD, PhD
• Phone: 86-10-83572784
• Email: wangdongxin[@]hotmail.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Recruiting
• Enrollment: 174
• Est. completion date: July 2025
• Est. primary completion date: June 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 50 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Dexmedetomidine
• Esketamine
• Intensive Care Unit
• Mechanical Ventilation
• Sleep Quality

Intervention

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

Locations

Country	Name	City	State
China	Peking University First Hospital	Beijing	Beijing

Sponsors (1)

Lead Sponsor	Collaborator
Peking University First Hospital

Country where clinical trial is conducted

China, 

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* Note: There are 45 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Length of hospital stay	Length of hospital stay.	Up to 30 days after enrollment
Other	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
Other	All-cause mortality within 30 days	All-cause mortality within 30 days	Up to 30 days after enrollment
Other	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
Other	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
Other	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
Other	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
Other	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
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	Duration of mechanical ventilation	Mechanical ventilation during ICU stay.	Up to 30 days after enrollment
Secondary	Length of ICU stay	Length of ICU stay.	Up to 30 days after enrollment