Dexmedetomidine and Outcomes of Elderly Admitted to ICU After Surgery

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

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.

Study Overview

• Status: Recruiting
• Conditions: Surgery; Elderly; Dexmedetomidine; Intensive Care Unit; Overall Survival
• Intervention / Treatment: Drug: Dexmedetomidine; Drug: Placebo

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 Type: Interventional
• Enrollment (Estimated): 1410
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Dong-Xin Wang, MD, PhD; Phone Number: (86)10-83572784; Email: wangdongxin@hotmail.com
• Study Contact Backup: Name: Zhao-Ting Meng, MD; Phone Number: (86)10-83575138; Email: 526589053@qq.com

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100034
      • Recruiting
      • Peking University First Hospital
      • Contact: Dong-Xin Wang, MD, PhD; Phone Number: (86) 10-83572784; Email: wangdongxin@hotmail.com
      • Contact: Zhao-Ting Meng, MD; Phone Number: (86) 10-83575138; Email: 526589053@qq.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 65 years and older (Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall survival after surgery	Overall survival after surgery	Up to 4 years after surgery

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Length of stay in hospital after surgery	Length of stay in hospital after surgery	Up to 30 days after surgery
The incidence of organ injury within 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).	Up to 5 days after surgery
Length of stay in the intensive care unit (ICU) stay after surgery	Length of ICU stay after surgery	Up to 30 days after surgery
Incidence of postoperative complications within 30 days after surgery	Postoperative complications are defined as newly occured medical events that are harmful to patients' recovery and required interventional therapy.	Up to 30 days after surgery
Rate of all-cause 30-day mortality after surgery	All-cause 30-day mortality after surgery	Up to 30 days after surgery
Sleep quality 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).	At 30 days after surgery
Recurrence-free survival after surgery	Recurrence-free survival after surgery	Up to 4 year after surgery
Event-free survival after surgery	Event-free survival after surgery	Up to 4 year after surgery
Cancer-specific survival after surgery	Cancer-specific survival after surgery	Up to 4 year after surgery
Quality of life in 1-year survivors 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).	At the end the 1st year after surgery

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pain severity within 5 days after surgery: Numeric Rating Scale	Pain severity is assessed with the Numeric Rating Scale (an 11-point scale where 0=no pain and 10=the worst pain.	Up to 5 days after surgery.
Subjective sleep quality within 5 days after surgery: Numeric Rating Scale	Subjective sleep quality the Numeric Rating Scale (an 11-point scale where 0=the best sleep and 10=the worst sleep.	Assessed in the morning on the 1st, 2nd, 3rd, 4th, and 5th day after surgery
Overall survival after surgery in cancer patients	Overall survival after surgery in cancer patients	Up to 4 year after surgery
Recurrence-free survival after surgery in cancer patients	Recurrence-free survival after surgery in cancer patients	Up to 4 year after surgery
Event-free survival after surgery in cancer patients	Event-free survival after surgery in cancer patients	Up to 4 year after surgery
Cancer-specific survival after surgery in cancer patients	Cancer-specific survival after surgery in cancer patients	Up to 4 year after surgery

Collaborators and Investigators

• Sponsor: Peking University First Hospital
• Collaborators: Peking University Third Hospital; Beijing Hospital
• Investigators: Principal Investigator: Dong-Xin Wang, MD, PhD, Peking University First Hospital

Publications and helpful links

General Publications

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Study record dates

Study Major Dates

• Study Start (Actual): August 28, 2020
• Primary Completion (Estimated): January 1, 2025
• Study Completion (Estimated): January 1, 2025

Study Registration Dates

• First Submitted: December 17, 2019
• First Submitted That Met QC Criteria: December 18, 2019
• First Posted (Actual): December 19, 2019

Study Record Updates

• Last Update Posted (Actual): September 21, 2023
• Last Update Submitted That Met QC Criteria: September 17, 2023
• Last Verified: September 1, 2023

More Information

Terms related to this study

• Keywords: Elderly; Surgery; Intensive Care Unit; Dexmedetomidine; Overall survival
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Analgesics, Non-Narcotic; Adrenergic alpha-2 Receptor Agonists; Adrenergic alpha-Agonists; Adrenergic Agonists; Hypnotics and Sedatives; Dexmedetomidine
• Other Study ID Numbers: 2019-226

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No