Night-time Dexmedetomidine-esketamine Infusion and Sleep Quality in ICU Patients

Peking University

Status and phase: Completed; Phase 4

Conditions: Esketamine; Sleep Quality; Dexmedetomidine; Intensive Care Unit; Mechanical Ventilation

Treatments: Drug: Routine sedation and analgesia; Drug: Dexmedetomidine-esketamine

Study type: Interventional

Funder types: Other

Identifiers

NCT05718024

2023-006

Details and patient eligibility

About

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.

Full 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.

Enrollment: 174 patients

Sex: All

Ages: 50+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

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174 participants in 2 patient groups

Dexmedetomidine-esketamine

Experimental group

Description:

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, for a duration of up to 5 days.

Treatment:

Drug: Dexmedetomidine-esketamine

Control

Active Comparator group

Description:

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), for a duration of up to 5 days.

Treatment:

Drug: Routine sedation and analgesia