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

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.

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.

Eligibility Criteria:
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.