Endothelial Injury Mechanism in Elderly Patients Undergoing Major Surgery

NCT ID: NCT03639896

Last Updated: 2021-02-10

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 464 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-07-01
• Study Completion Date: 2020-10-31

Brief Summary

The incidence of postoperative cognitive injury is high in elderly patients, especially after major surgery. The relevant pathophysiological mechanisms are still unclear, and the possible mechanisms that have been proposed so far include inflammation, neurotransmitter imbalance and metabolic disorders. In recent years, clinical studies of acute brain dysfunction after vascular endothelial injury have attracted attention.

Degradation of the endothelial glycocalyx layer and subsequent shedding of its constituents is seen as an early marker of endothelial injury, and may increase vascular permeability.Many preclinical and clinical studies have demonstrated an association between inflammatory cytokines such as TNF-α, IL-1β, IL-6, and IL-10 and glycocalyx degradation biomarkers.

The scholars found evidence of plasma endothelial injury after abdominal open surgery in the elderly. Dexmedetomidine could attenuate stress response such as TNF-α, IL-1β and IL-6. Based on the above evidence, we hypothesize that elderly patients experience inflammatory response secondary to surgical traumatic stress after major surgery, greatly increasing the degree of endothelial injury (heparan sulphate and syndecan-1), reducing brain perfusion while increasing Blood-brain barrier permeability (S100B level), promoting the release of cytokines Interleukin-2(IL-2), Interleukin-6(IL-6), tumor necrosis factor-alpha(TNF-α) ,and vascular endothelial growth factor (VEGF) while reducing brain-derived neurotrophic factor(BDNF) synthesis, then leading to postoperative acute spasm. We would test the hypothesis that can reverse these effects and improve cognitive deficits.

Conditions

Endothelial Dysfunction; Blood Brain Barrier Defect; Postoperative Cognitive Dysfunction

Study Design

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

Study Groups

Dexmedetomidine

0.5μg/kg Dexmedetomidine as initial loading dose is given for 15 minutes before induction of anesthesia, followed by a maintenance infusion of 0.4μg/kg/h and stopped 30 minutes before the surgery over.

Group Type: EXPERIMENTAL

Dexmedetomidine

Intervention Type: DRUG

0.5μg/kg Dexmedetomidine as initial loading dose is given for 15 minutes before induction of anesthesia, followed by a maintenance infusion of 0.4μg/kg/h and stopped 30 minutes before the surgery over.

Controlled

0.5μg/kg Saline as initial loading dose is given for 15 minutes before induction of anesthesia, followed by a maintenance infusion of 0.4μg/kg/h and stopped 30 minutes before the surgery over.

Group Type: PLACEBO_COMPARATOR

Saline

Intervention Type: DRUG

0.5μg/kg saline as initial loading dose is given for 15 minutes before induction of anesthesia, followed by a maintenance infusion of 0.4μg/kg/h and stopped 30 minutes before the surgery over.

Interventions

Dexmedetomidine

0.5μg/kg Dexmedetomidine as initial loading dose is given for 15 minutes before induction of anesthesia, followed by a maintenance infusion of 0.4μg/kg/h and stopped 30 minutes before the surgery over.

Intervention Type: DRUG

Saline

0.5μg/kg saline as initial loading dose is given for 15 minutes before induction of anesthesia, followed by a maintenance infusion of 0.4μg/kg/h and stopped 30 minutes before the surgery over.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

1. Written informed consent;

2. Patients undergoing selective major gastrointestinal surgery with laparoscope and general anesthesia;

3. Age 65-90 yrs;

4. Anesthesia Society of American (ASA) Scale II~IV;

5. Anticipated surgery time 2-6 hrs;

Exclusion Criteria

1. Dementia patients（Mini-mental state examination< 20）

2. Factors existed that affect cognition assessment such as language,visual,and auditory dysfunction；

3. Unstable metal status and mental disease；

4. A hematocrit value less than 28%in perioperative period;

5. Patients with abnormal preoperative inflammatory indicators（Higher white blood cell and C-reactive protein);

6. Patients undergoing cardiac and neural surgery;

7. Parkinson's Disease；

8. Sure or suspected abuse of analgesic and sedation drug.

• Minimum Eligible Age: 65 Years
• Maximum Eligible Age: 90 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Hangzhou Cancer Hospital

OTHER

Sponsor Role: collaborator

The First Affiliated Hospital of Anhui Medical University

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Xinqi Cheng, PhD

Role: PRINCIPAL_INVESTIGATOR

The First Affiliated Hospital of Anhui Medical University

Locations

The First Affiliated Hospital of Anhui Medical University

Hefei, Anhui, China

Hangzhou cancer hospital

Hangzhou, Zhejiang, China

Countries

China

Other Identifiers

7742

Identifier Type: -

Identifier Source: org_study_id