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

NCT ID: NCT04111926

Last Updated: 2022-04-20

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 619 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-10-07
• Study Completion Date: 2021-04-01

Brief Summary

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

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.

Conditions

Overall Survival

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: QUADRUPLE

Study Groups

Intervention group

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.

Group Type: EXPERIMENTAL

Dexmedetomidine

Intervention Type: DRUG

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.

Control group

Volume-matched normal saline was administered in the same rate for the same duration as in the intervention group.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Volume-matched normal saline was administered in the same rate for the same duration as in the intervention group.

Interventions

Dexmedetomidine

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.

Intervention Type: DRUG

Placebo

Volume-matched normal saline was administered in the same rate for the same duration as in the intervention group.

Intervention Type: DRUG

Other Intervention Names

Dexmedetomidine Hydrochloride; Normal saline

Eligibility Criteria

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.

• Minimum Eligible Age: 60 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Peking University First Hospital

OTHER

Sponsor Role: lead

Responsible Party

Dong-Xin Wang

Professor and Chairman, Department of Anesthesiology and Critical Care Medicine

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Dong-Xin Wang, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Peking University First Hospital

Locations

Peking University First Hospital

Beijing, Beijing Municipality, China

Countries

China

References

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Reference Type: BACKGROUND

PMID: 23717223 (View on PubMed)

Jalonen J, Hynynen M, Kuitunen A, Heikkila H, Perttila J, Salmenpera M, Valtonen M, Aantaa R, Kallio A. Dexmedetomidine as an anesthetic adjunct in coronary artery bypass grafting. Anesthesiology. 1997 Feb;86(2):331-45. doi: 10.1097/00000542-199702000-00009.

Reference Type: BACKGROUND

PMID: 9054252 (View on PubMed)

Li Y, Wang B, Zhang LL, He SF, Hu XW, Wong GT, Zhang Y. Dexmedetomidine Combined with General Anesthesia Provides Similar Intraoperative Stress Response Reduction When Compared with a Combined General and Epidural Anesthetic Technique. Anesth Analg. 2016 Apr;122(4):1202-10. doi: 10.1213/ANE.0000000000001165.

Reference Type: BACKGROUND

PMID: 26991622 (View on PubMed)

Su X, Meng ZT, Wu XH, Cui F, Li HL, Wang DX, Zhu X, Zhu SN, Maze M, Ma D. Dexmedetomidine for prevention of delirium in elderly patients after non-cardiac surgery: a randomised, double-blind, placebo-controlled trial. Lancet. 2016 Oct 15;388(10054):1893-1902. doi: 10.1016/S0140-6736(16)30580-3. Epub 2016 Aug 16.

Reference Type: BACKGROUND

PMID: 27542303 (View on PubMed)

Zhang DF, Su X, Meng ZT, Li HL, Wang DX, Xue-Ying Li, Maze M, Ma D. Impact of Dexmedetomidine on Long-term Outcomes After Noncardiac Surgery in Elderly: 3-Year Follow-up of a Randomized Controlled Trial. Ann Surg. 2019 Aug;270(2):356-363. doi: 10.1097/SLA.0000000000002801.

Reference Type: BACKGROUND

PMID: 29742525 (View on PubMed)

Wang BJ, Li CJ, Hu J, Li HJ, Guo C, Wang ZH, Zhang QC, Mu DL, Wang DX. Impact of dexmedetomidine infusion during general anaesthesia on incidence of postoperative delirium in elderly patients after major non-cardiac surgery: study protocol of a randomised, double-blinded and placebo-controlled trial. BMJ Open. 2018 Apr 21;8(4):e019549. doi: 10.1136/bmjopen-2017-019549.

Reference Type: BACKGROUND

PMID: 29680809 (View on PubMed)

Cata JP, Singh V, Lee BM, Villarreal J, Mehran JR, Yu J, Gottumukkala V, Lavon H, Ben-Eliyahu S. Intraoperative use of dexmedetomidine is associated with decreased overall survival after lung cancer surgery. J Anaesthesiol Clin Pharmacol. 2017 Jul-Sep;33(3):317-323. doi: 10.4103/joacp.JOACP_299_16.

Reference Type: BACKGROUND

PMID: 29109628 (View on PubMed)

Gerresheim G, Schwemmer U. [Dexmedetomidine]. Anaesthesist. 2013 Aug;62(8):661-74. doi: 10.1007/s00101-013-2206-6. German.

Reference Type: BACKGROUND

PMID: 23917892 (View on PubMed)

Xing MW, Li CJ, Guo C, Wang BJ, Mu DL, Wang DX. Effect of intraoperative dexmedetomidine on long-term survival in older patients after major noncardiac surgery: 3-year follow-up of a randomized trial. J Clin Anesth. 2023 Jun;86:111068. doi: 10.1016/j.jclinane.2023.111068. Epub 2023 Feb 1.

Reference Type: DERIVED

PMID: 36736209 (View on PubMed)

Other Identifiers

2019-0927

Identifier Type: -

Identifier Source: org_study_id