Clinical trial NCT03172897: Low-dose Dexmedetomidine in Mechanically Ventilated ICU Patients
Official title: Low-dose Dexmedetomidine for Delirium Prevention in Mechanically Ventilated Patients in Intensive Care Unit: a Multicenter, Randomised, Double-blinded, Placebo-controlled Trial
Study type: INTERVENTIONAL
Overall status: SUSPENDED
Phase: PHASE4
Conditions: Adult Disease
Intensive Care Unit Syndrome
Mechanical Ventilation Complication
Delirium
Dexmedetomidine
Keywords: Adult
Intensive care unit
Mechanical ventilation
Delirium
Dexmedetomidine
Lead sponsor: Peking University First Hospital
Sponsor class: OTHER
Collaborators: name: Peking University Third Hospital
First posted: 2017-06-01
Enrollment: 260
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: For patients undergoing mechanical ventilation, 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, low-dose dexmedetomidine without sedative effects (0.1 ug/kg/h) improved sleep quality and reduced the incidence of delirium in elderly patients admitted to the ICU after surgery. The investigators hypothesize that, for ICU patients with prolonged mechanical ventilation, low-dose dexmedetomidine infusion (0.1 ug/kg/h) may also be effective in decreasing delirium. The purpose of this study is to investigate whether low-dose dexmedetomidine infusion can reduce the incidence of delirium in ICU patients with prolonged duration of mechanical ventilation (\>= 24 hours).

Detailed description: Delirium is an acutely occurred and transient brain dysfunction characterized with cognitive dysfunction, lowered consciousness, disturbed attention, abnormal psychoactivity, and disordered sleep-wake rhythm. Delirium is frequent in mechanically ventilated patients in the intensive care unit (ICU), with reported incidences up to 70% or 87%. Possible reasons leading to delirium include the intervention-heavy environment of the ICU, mechanical ventilation and sleep disturbances. The occurrence of delirium is associated with worse outcomes including prolonged mechanical ventilation and ICU stay, increased complications, prolonged hospital stay, higher mortality, and elevated medical expenses. It is also associated with worse long-term outcomes including declined cognitive function, lowered life quality, and elevated long-term mortality.

Dexmedetomidine is a high selective alpha-2 adrenoceptor agonist with anxiolytic, sedative and analgesic effects. When used for sedation in mechanically ventilated patients (dose range 0.2-1.4 ug/kg/h), it reduces the consumption of other sedatives and analgesics, ameliorates the rhythm and structure of sleep, and decreases the occurrence of delirium. In recent studies of the investigators, low-dose dexmedetomidine infusion (0.1 ug/kg/h) ameliorated sleep quality; for elderly patients admitted to the ICU after surgery, prophylactic low-dose dexmedetomidine infusion reduced the incidence of delirium (for patients with mechanical ventilation: 28.8% with placebo vs. 11.5% with dexmedetomidine, P\<0.0001; for patients without mechanical ventilation: 15.1% with placebo vs. 6.3% with dexmedetomidine, P=0.014).

For patients undergoing mechanical ventilation, 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. Some authors even reported that no sedation (analgesia only) provides better outcome than light sedation, because it further shortens the durations of mechanical ventilation and ICU stay. In the above studies of the investigators, the recruited patients were less severe because the Acute Physiology and Chronic Health Evaluation II (APACHE II) score was low (mean score from 10.2 to 10.6) and the duration of mechanical ventilation was short (median 6.9 hours in the control group). The investigators hypothesize that, for ICU patients with prolonged mechanical ventilation, low-dose dexmedetomidine infusion (0.1 ug/kg/h) may also be effective in improving sleep and decreasing delirium. The purpose of this study is to investigate whether low-dose dexmedetomidine infusion can reduce the incidence of delirium in ICU patients with prolonged duration of mechanical ventilation (\>= 24 hours).

Eligibility criteria: Inclusion Criteria:

* aged 18 years or older;
* admitted to the ICU;
* with expected duration of mechanical ventilation of more than 24 hours.

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 \[bpm\]), or second degree or greater atrioventricular block without pacemaker;
* severe hepatic dysfunction (Child-Pugh class C);
* severe renal dysfunction (undergoing dialysis before surgery);
* less likely to survive for more than 24 hours.

Primary outcomes:
measure: Incidence of delirium within the first 7 days after enrollment
timeFrame: From enrollment until 7 days.
Secondary outcomes:
measure: Duration of mechanical ventilation
timeFrame: From enrollment until extubation or 30 days.
measure: Length of stay in the ICU
timeFrame: From enrollment until ICU discharge or 30 days.
measure: Length of stay in the hospital
timeFrame: From enrollment until hospital discharge or 30 days.
measure: Occurrence of non-delirium complications
timeFrame: From enrollment until 30 days.
measure: All-cause 30-day mortality
timeFrame: On the 30th day after enrollment.
measure: 30-day cognitive function
timeFrame: On the 30th day after enrollment.
measure: 30-day life quality
timeFrame: On the 30th day after enrollment.
Other outcomes:
measure: Pain intensity
timeFrame: From enrollment until 7 days.
measure: Subjective sleep quality
timeFrame: From enrollment until 7 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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