Dexmedetomidine and Outcomes of Elderly Admitted to ICU After Surgery

Sponsor

Peking University First Hospital (Other)

Overall Status

Recruiting

CT.gov ID

NCT04204798

Collaborator

Peking University Third Hospital (Other), Beijing Hospital (Other)

1,410

Enrollment

Location

Arms

40.1

Anticipated Duration (Months)

35.1

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Elderly Surgery Intensive Care Unit Dexmedetomidine Overall Survival	Drug: Dexmedetomidine Drug: Placebo	N/A

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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

1410 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Prevention

Official Title:

Impact of Low-dose Dexmedetomidine on Outcomes of Elderly Admitted to ICU After Noncardiac Surgery: a Randomized Controlled Trial

Actual Study Start Date :

Aug 28, 2020

Anticipated Primary Completion Date :

Jan 1, 2024

Anticipated Study Completion Date :

Jan 1, 2024

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Dexmedetomidine group Dexmedetomidine is infused from 4 pm to 8 am during ICU stay for no more than 3 days.	Drug: Dexmedetomidine Dexmedetomidine is infused from 4 pm to 8 am during ICU stay for no more than 3 days. 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. 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.
Placebo Comparator: Placebo group Normal saline is infused for the same duration as in the dexmedetomidine group.	Drug: Placebo Normal saline is infused in the same rate for the same duration as in the dexmedetomidine group. Propofol sedation is administered when considered necessary. Other Names: Normal saline

Arm

Intervention/Treatment

Experimental: Dexmedetomidine group

Dexmedetomidine is infused from 4 pm to 8 am during ICU stay for no more than 3 days.

Drug: Dexmedetomidine

Dexmedetomidine is infused from 4 pm to 8 am during ICU stay for no more than 3 days. 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. 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.

Placebo Comparator: Placebo group

Normal saline is infused for the same duration as in the dexmedetomidine group.

Drug: Placebo

Normal saline is infused in the same rate for the same duration as in the dexmedetomidine group. Propofol sedation is administered when considered necessary.

Other Names:

Normal saline

Outcome Measures

Primary Outcome Measures

Overall survival after surgery [Up to 4 years after surgery]
Overall survival after surgery

Secondary Outcome Measures

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
Length of stay in hospital after surgery [Up to 30 days after surgery]
Length of stay in hospital 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.
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).

Other Outcome Measures

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.
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

Eligibility Criteria

Criteria

Ages Eligible for Study:

65 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.