Clinical trial NCT03335527: Impacts of Low-Dose Dexmedetomidine on Sleep Quality in Mechanically Ventilated ICU Patients
Official title: Impact of Low-Dose Dexmedetomidine on Sleep Quality in Mechanical Ventilation Patients After Surgery in Intensive Care Unit: a Pilot Randomized, Double-Blind, Placebo-Controlled Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Aged
Postoperative Period
Intensive Care Units
Mechanical Ventilation Complication
Sleep Disorders
Dexmedetomidine
Keywords: Aged
Postoperative period
Intensive Care Unit
Mechanical ventilation
Sleep quality
Dexmedetomidine
Lead sponsor: Peking University First Hospital
Sponsor class: OTHER
First posted: 2017-11-07
Enrollment: 80
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: Sleep disturbances frequently occur in intensive care unit (ICU) patients undergoing mechanical ventilation. In a previous study, sedative dose dexmedetomidine (median 0.6 microgram/kg/h) improved sleep quality in mechanically ventilated patients. However, for mechanically ventilated patients, light sedation is better than deep sedation for the outcomes, which is manifested as shortened length of ICU stay, shortened duration of mechanical ventilation, and decreased mortality. In a recent study of the investigators, non-sedative low-dose dexmedetomidine (0.1 microgram/kg/h) improved sleep quality in non-mechanically ventilated elderly patients admitted to the ICU after surgery. The investigators hypothesize that, in mechanically ventilated patients who are admitted to the ICU after surgery, low-dose dexmedetomidine may also improve sleep quality.

Detailed description: Sleep is severely disturbed in mechanically ventilated ICU patients, especially those after surgery. Polysomnographic studies performed in these patients demonstrated a severe increase in sleep fragmentation, prolonged N1 and N2 sleep, reduced N3 and REM sleep, and an abnormal distribution of sleep because almost half of the total sleep time occurred during the daytime. Patients reported little or no sleep, poor sleep quality, frequent awakening, and daytime sleep.

Many factors are responsible for sleep disturbance in postoperative ICU patients with mechanical ventilation, these include the severity of surgical stress and illness, ICU environment, mechanical ventilation, pain, sedatives and analgesics, and various other therapy. Sleep disturbances produce harmful effects on postoperative outcomes. It is associated with increased prevalence of delirium, cardiac events and worse functional recovery. Moreover, patients with sleep disturbances are more sensitive to pain.

Unlike other sedative agents, dexmedetomidine exerts its sedative effects through an endogenous sleep-promoting pathway and produces a N2 sleep-like state. In mechanically ventilated ICU patients, nighttime infusion of sedative dose of dexmedetomidine (median 0.6 microgram/kg/h) preserved the day-night cycle of sleep and improved the sleep architecture by increasing sleep efficiency and stage N2 sleep.

Studies showed that, in mechanically ventilated patients, light sedation is better than deep sedation for patients' outcomes, including shortened duration of ventilation and length of ICU stay, and decreased mortality. Some studies even showed that no sedation (analgesia only) is better than sedation. In a recent study of non mechanical ventilated elderly patients who were admitted to the ICU after surgery, non-sedative low-dose dexmedetomidine infusion (at a rate of 0.1 microgram/kg/h during the night on the day of surgery) increased the percentage of stage N2 sleep (and decreased the percentage of N1 sleep), prolonged the total sleep time, increased the sleep efficiency, and improved the subjective sleep quality.

The investigators hypothesize that, in mechanically ventilated patients who were admitted to the ICU after surgery, low-dose dexmedetomidine infusion may also improve sleep quality.

Eligibility criteria: Inclusion Criteria:

* aged 18 years or older;
* admitted to the ICU after surgery;
* with an expected duration of mechanical ventilation of more than 12 hours (admitted before 21:00 on the day of surgery and extubated after 06:00 on the first day after surgery).

Exclusion Criteria:

* refused to participate;
* aged less than 18 years;
* pregnant;
* preoperative history of schizophrenia, epilepsy, parkinsonism, or myasthenia gravis;
* inability to communicate in the preoperative period (coma, profound dementia, or language barrier);
* brain injury or neurosurgery;
* known preoperative left ventricular ejection fraction less than 30%, sick sinus syndrome, severe sinus bradycardia (\<50 beats per min), or second degree or greater atrioventricular block without pacemaker, systolic blood pressure less than 90 mmHg despite continuous infusions of vasopressors before the start of study drugs infusion;
* serious hepatic dysfunction (Child-Pugh class C);
* serious renal dysfunction (undergoing dialysis before surgery);
* less likelihood to survive for more than 24 hours;
* preoperative history of sleep disorders (requirement of hypnotics/sedatives during the last month) or history of obstructive sleep apnea syndrome (diagnosed with obstructive sleep apnea);
* allergy to the study drugs;
* other conditions that are considered unsuitable for study participation.

Primary outcomes:
measure: Sleep quality during the night of surgery.
timeFrame: Assessed at 08:00 on the first day after surgery.
Secondary outcomes:
measure: Incidence of delirium within the first 7 days after surgery.
timeFrame: Assessed twice daily during the first 7 days after surgery.
measure: Sleep quality within the first 7 days after surgery.
timeFrame: Assessed once daily during the first 7 days after surgery.
measure: Total sleep time
timeFrame: Monitored with polysomnograph during the night of surgery.
measure: Sleep efficiency
timeFrame: Monitored with polysomnograph during the night of surgery.
measure: Fragmented sleep index
timeFrame: Monitored with polysomnograph during the night of surgery.
measure: Percentages of sleep stages
timeFrame: Monitored with polysomnograph during the night of surgery.
measure: Duration of mechanical ventilation.
timeFrame: From ICU admission to 30 days after surgery.
measure: Length of stay in the ICU.
timeFrame: From ICU admission to 30 days after surgery.
measure: Length of stay in the hospital after surgery.
timeFrame: From date of surgery to 30 days after surgery.
measure: Occurrence of postoperative complications.
timeFrame: From date of surgery to 30 days after surgery.
measure: All-cause 30-day mortality.
timeFrame: On the 30th day after surgery.
measure: 30-day cognitive function.
timeFrame: On the 30th day after surgery.
measure: 30-day quality of life.
timeFrame: On the 30th day after surgery.
measure: 30-day sleep quality.
timeFrame: On the 30th day after surgery.
Other outcomes:
measure: Pain intensity.
timeFrame: Assessed during the first 7 days after surgery.
measure: Score of Acute Physiology and Chronic Health Evaluation II (APACHE II).
timeFrame: Assessed within 24 hours after ICU admission.
measure: Percentage of time within the target of sedation during mechanical ventilation.
timeFrame: During mechanical ventilation, for a maximum of 3 days.
Locations:
city: Beijing
country: China
facility: Peking University First Hospital
state: Beijing
Study officials:
affiliation: Peking University First Hospital
name: Dong-Xin Wang, MD, PhD
role: PRINCIPAL_INVESTIGATOR
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