Dexmedetomidine, Elderly, Intensive Care Unit, Overall Survival, Surgery
Conditions
Keywords
Elderly, Surgery, Intensive Care Unit, Dexmedetomidine, Overall survival
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.
Interventions
DRUGDexmedetomidine
1. Dexmedetomidine is infused from 4 pm to 8 am during ICU stay for no more than 3 days. 2. For non-intubated patients, the infusion rate is adjusted to reach a Richmond Agitation-Sedation Scale (RASS) of -1, or a maximal rate of 0.2 microgram/kg/h, or the occurrence of any adverse events. 3. For intubated patients, the infusion rate is adjusted to reach a RASS of -1, or a maximal rate of 0.7 microgram/kg/h, or the occurrence of any adverse events.
DRUGPlacebo
1. Normal saline is infused in the same rate for the same duration as in the dexmedetomidine group. 2. Propofol sedation is administered when considered necessary.
Sponsors
Peking University Third Hospital
Beijing Hospital
Peking University First Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
65 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall survival after surgery | Up to 4 years after surgery | Overall survival after surgery |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Length of stay in hospital after surgery | Up to 30 days after surgery | Length of stay in hospital after surgery |
| Rate of all-cause 30-day mortality after surgery | Up to 30 days after surgery | All-cause 30-day mortality after surgery |
| Sleep quality at 30 days after surgery | At 30 days after surgery | The sleep quality is assessed with the Pittsburgh Sleep Quality Index Questionnaire (PSQI, score ranges from 0 to 21, with higher score indicating poorer sleep quality). |
| Recurrence-free survival after surgery | Up to 4 year after surgery | Recurrence-free survival after surgery |
| Event-free survival after surgery | Up to 4 year after surgery | Event-free survival after surgery |
| Cancer-specific survival after surgery | Up to 4 year after surgery | Cancer-specific survival after surgery |
| Quality of life in 1-year survivors after surgery | At the end the 1st year after surgery | The quality of life is assessed with the World Health Organization Quality of Life Questionaire abbreviated version (WHOQOL-BREF, a 24-item questionnaire that provides assessments of the quality of life in physical, psychological, and social relationship, and environmental domains. For each domain, the score ranges from 0 to 100, with higher score indicating better function). |
| The incidence of organ injury within 5 days after surgery | Up to 5 days after surgery | Organ injury include delirium (assessed with Confusion Assessment Method/CAM for the Intensive Care Unit), acute kidney injury (assessed with KIDGO criteria), and myocardial injury (assessed with cardiac troponin I). |
| Length of stay in the intensive care unit (ICU) stay after surgery | Up to 30 days after surgery | Length of ICU stay after surgery |
| Incidence of postoperative complications within 30 days after surgery | Up to 30 days after surgery | Postoperative complications are defined as newly occured medical events that are harmful to patients' recovery and required interventional therapy. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Overall survival after surgery in cancer patients | Up to 4 year after surgery | Overall survival after surgery in cancer patients |
| Recurrence-free survival after surgery in cancer patients | Up to 4 year after surgery | Recurrence-free survival after surgery in cancer patients |
| Event-free survival after surgery in cancer patients | Up to 4 year after surgery | Event-free survival after surgery in cancer patients |
| Cancer-specific survival after surgery in cancer patients | Up to 4 year after surgery | Cancer-specific survival after surgery in cancer patients |
| Pain severity within 5 days after surgery: Numeric Rating Scale | Up to 5 days after surgery. | Pain severity is assessed with the Numeric Rating Scale (an 11-point scale where 0=no pain and 10=the worst pain. |
| Subjective sleep quality within 5 days after surgery: Numeric Rating Scale | Assessed in the morning on the 1st, 2nd, 3rd, 4th, and 5th day after surgery | Subjective sleep quality the Numeric Rating Scale (an 11-point scale where 0=the best sleep and 10=the worst sleep. |
Countries
China
Outcome results
None listed