Clinical trial NCT04204798: Dexmedetomidine and Outcomes of Elderly Admitted to ICU After Surgery
Official title: Impact of Low-dose Dexmedetomidine on Outcomes of Elderly Admitted to ICU After Noncardiac Surgery: a Randomized Controlled Trial
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Elderly
Surgery
Intensive Care Unit
Dexmedetomidine
Overall Survival
Keywords: Elderly
Surgery
Intensive Care Unit
Dexmedetomidine
Overall survival
Lead sponsor: Peking University First Hospital
Sponsor class: OTHER
Collaborators: name: Peking University Third Hospital
name: Beijing Hospital
First posted: 2019-12-19
Enrollment: 1410
Sex: ALL
Minimum age (years): 65
Standard ages: OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: Sleep disorder and delirium are common problems in intensive care unit (ICU) patients, and may lead to poor prognosis. The investigators' previous study showed that nighttime infusion of low-dose dexmedetomidine improved the sleep quality and decreased the incidence of delirium in ICU patients after surgery. Long-term follow-up of these patients showed that low-dose dexmedetomidine also improved 2-year survival and the quality of life in 3-year survivors. The purpose of this study is to investigate the effect of low-dose dexmedetomidine on the long-term outcome of elderly patients admitted to the ICU after noncardiac surgery.

Detailed description: Dexmedetomidine is a highly selective α2-adrenoceptor agonist with sedative, analgesic and anti-anxiety properties. Unlike other sedative agents, dexmedetomidine exerts its sedative effects through an endogenous sleep-promoting pathway, producing a state like non-rapid eye movement sleep. For mechanically ventilated patients, sedative-dose dexmedetomidine infusion at night maintains circadian rhythm, increases sleep efficiency, and improves sleep architecture. When used for sedation in mechanical ventilated patients, it reduces the incidence of delirium.

Dexmedetomidine may improve patient outcomes by improving sleep quality. A previous randomized trial found that, for elderly patients who were admitted to ICU after noncardiac surgery, nighttime infusion of low-dose dexmedetomidine significantly improves the sleep quality and decreases the incidence of postoperative delirium. A long-term follow-up of these patients showed that low-dose dexmedetomidine infusion significantly increased survival up to 2 years, and improved cognitive function and quality of life in 3-year survivors.

In the study mentioned above, dexmedetomidine was only infused during the night after surgery with a fixed dose. The investigators hypothesize that, for elderly admitted to ICU after surgery, nighttime infusion of individualized low-dose dexmedetomidine may improve long-term outcomes. This randomized controlled trial is designed to investigate the effect of low-dose dexmedetomidine on 1-year survival and the quality of life of 1-year survivors in elderly patients admitted to the ICU after surgery.

Eligibility criteria: Inclusion Criteria:

* Age ≥65 years old;
* Admitted to intensive care unit (ICU) after noncardiac surgery;
* Expected to stay in ICU until the next morning. For those with endotracheal intubation, the expected duration of mechanical ventilation is \<24 hours;
* Provide written informed consents.

Exclusion Criteria:

* Preoperative history of schizophrenia, epilepsy, Parkinsonism, or myasthenia gravis;
* Inability to communicate in the preoperative period (coma, profound dementia, or language barrier);
* Preoperative history of sleep apnea (previous diagnosis; or STOP-Bang score ≥3 with serum bicarbonate ≥ 28 mmol/L);
* Known sick sinus syndrome, severe sinus bradycardia (\<50 beats per min \[bpm\]), or second degree or higher atrioventricular block without pacemaker;
* Hypotension (systolic blood pressure \[SBP\] \<90 mmHg, mean arterial pressure \[MAP\] \<70 mmHg, or a decrease of SBP \>30% of baseline) or in a state of shock (vasopressors are required to maintain MAP ≥65 mmHg and serum lactate \>2 mmol/L);
* Severe hepatic dysfunction (Child-Pugh class C), renal failure (requirement of renal replacement therapy), or expected survival \<24 hours;
* Traumatic brain injury or neurosurgery;
* Presence of delirium before surgery (assessed with Confusion Assessment Method \[CAM\]/CAM-ICU);
* Undergoing treatment of dexmedetomidine or clonidine;
* Other conditions that are considered unsuitable for study participation.

Primary outcomes:
measure: Overall survival after surgery
timeFrame: Up to 4 years after surgery
Secondary outcomes:
measure: The incidence of organ injury within 5 days after surgery
timeFrame: Up to 5 days after surgery
measure: Length of stay in the intensive care unit (ICU) stay after surgery
timeFrame: Up to 30 days after surgery
measure: Length of stay in hospital after surgery
timeFrame: Up to 30 days after surgery
measure: Incidence of postoperative complications within 30 days after surgery
timeFrame: Up to 30 days after surgery
measure: Rate of all-cause 30-day mortality after surgery
timeFrame: Up to 30 days after surgery
measure: Sleep quality at 30 days after surgery
timeFrame: At 30 days after surgery
measure: Recurrence-free survival after surgery
timeFrame: Up to 4 year after surgery
measure: Event-free survival after surgery
timeFrame: Up to 4 year after surgery
measure: Cancer-specific survival after surgery
timeFrame: Up to 4 year after surgery
measure: Quality of life in 1-year survivors after surgery
timeFrame: At the end the 1st year after surgery
Other outcomes:
measure: Pain severity within 5 days after surgery: Numeric Rating Scale
timeFrame: Up to 5 days after surgery.
measure: Subjective sleep quality within 5 days after surgery: Numeric Rating Scale
timeFrame: Assessed in the morning on the 1st, 2nd, 3rd, 4th, and 5th day after surgery
measure: Overall survival after surgery in cancer patients
timeFrame: Up to 4 year after surgery
measure: Recurrence-free survival after surgery in cancer patients
timeFrame: Up to 4 year after surgery
measure: Event-free survival after surgery in cancer patients
timeFrame: Up to 4 year after surgery
measure: Cancer-specific survival after surgery in cancer patients
timeFrame: Up to 4 year after surgery
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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