Intraoperative Dexmedetomidine and Long-term Outcomes in Elderly After Major Surgery

Study Overview
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Brief Summary
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This is a 3-year follow-up of patients enrolled in a previous randomized controlled trial which showed that intraoperative dexmedetomidine reduced delirium in elderly patients after major non-cardiac surgery. The purpose of this study is to clarify the effects of intraoperative dexmedetomidine on long-term outcomes of these patients.

Detailed Description
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Dexmedetomidine is a highly selective α-2-receptor agonist with sedative, analgesic and anxiolytic effects. When used as an supplement during general anaesthesia, it reduces the consumption of the anaesthetics and relieves surgery-related stress response and inflammation. In a recent randomized ontrolled trial of the applicants, 620 elderly patients who underwent major non-cardiac surgery were randomized to receive dexmedetomidine or normal saline during general anesthesia. The results showed that use of dexmedetomidine reduced delirium (5.5% [17/309] with dexmedetomidine vs. 10.2% [32/310] with placebo, P=0.026) and 30-day non-delirium complications (9.4% [60/309] with dexmedetomidine vs. 26.1% [81/310] with placebo, P=0.047) after surgery. The effects of intraoperative dexmedetomidine on long-term outcomes after surgery remains unclear. In another study of the applicants, use of low-dose dexemeditomidine in ICU patients after surgery increased survival up to 2 years and improve quality of life in 3-year survivors. On the contrary, it was reported in a retrospective study that intraoperative use of dexmedetomidine was associated with shortened overall survival in patients after lung cancer surgery. Therefore, it is urgent to clarify the impact of intraoperative dexemeditomidine on long-term outcomes of patients undergoing major surgery, especially those undergoing cancer surgery. This study is a 3-year follow-up of patients who were enrolled in a randomzied controlled trial of the applicants in order to clarify the effects of intraoperative dexmedetomidine on long-term outcomes after surgery.

Official Title
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Impact of Intraoperative Dexmedetomidine on Long-term Outcomes in Elderly Patients After Major Non-cardiac Surgery: 3-year Follow-up of a Randomised Controlled Trial

Conditions
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Overall Survival

Intervention / Treatment
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* Drug: Dexmedetomidine
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Elderly patients (age ≥60 years); Scheduled to undergo elective major non-cardiac surgery with expected duration ≥2 hours under general anaesthesia. Exclusion Criteria: Do not provide written informed consent; Previous history of schizophrenia, epilepsy or Parkinson's disease; Visual, hearing, language or other barriers which impede communication and preoperative delirium assessment; History of traumatic brain injury; Severe bradycardia (heart rate <40 beats per minutes), sick sinus syndrome, or atrioventricular block of degree 2 or above without pacemaker; Severe hepatic dysfunction (Child-Pugh grade C); Renal failure (requirement of renal replacement therapy); Neurosurgery.

Ages Eligible for Study
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Minimum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Intervention group<br>A loading dose of dexmedetomidine (0.6 μg/kg) was administered during a 10-minute period before anaesthesia induction, followed by a continuous infusion at a rate of 0.5 μg/kg/hr till 1 hour before the end of surgery. | Drug: Dexmedetomidine<br>* A loading dose of dexmedetomidine (0.6 μg/kg) was administered during a 10-minute period before anaesthesia induction, followed by a continuous infusion at a rate of 0.5 μg/kg/hr till 1 hour before the end of surgery.<br>* Other names: Dexmedetomidine Hydrochloride;|
| Placebo Comparator: Control group<br>Volume-matched normal saline was administered in the same rate for the same duration as in the intervention group. | Drug: Placebo<br>* Volume-matched normal saline was administered in the same rate for the same duration as in the intervention group.<br>* Other names: Normal saline;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall survival within 3 years after surgery | Overall survival within 3 years after surgery | Up to 3 years after surgery. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Recurrence-free survival within 3 years after surgery. | Recurrence-free survival within 3 years after surgery. | Up to 3 years after surgery. | 
| Cancer-specific survival within 3 years after surgery. | Cancer-specific survival within 3 years after surgery. | Up to 3 years after surgery. | 
| Rate of new-onset disease or hospital readmission within 3 years after surgery. | Rate of new-onset disease or hospital readmission within 3 years after surgery. | Up to 3 years after surgery. | 
| Quality of life in 3-year survivors. | Quality of life is assessed with the World Health Organization Quality of Life-Brief Version. It assesses the quality of life at 4 domains, i.e., physical, psychological, social relationships, and environment. The score of each domain ranges from 0 to 100, with higher score indicating better quality of life. | At 3 years after surgery. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Elderly patients, Major non-cardiac surgery, Dexmedetomidine, long-term survival