Endothelial Injury Mechanism in Elderly Patients Undergoing Major Surgery

NCT03639896 | Completed Phase 4 DMC

• 1 other identifier: 7742
• Study Type: interventional
• Target: 464
• Locations: 1 country
• Sites: 2

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

Outcome Measures

Primary Outcomes (2)

• The change of incidence of postoperative delirium

  Through CAM-ICU to assess the incidence of the postoperative delirium.

  The 1st, 2nd and 7th day after the surgery.

• The change of incidence of postoperative cognition dysfunction

  The neuropsychological tests performed at the day before the surgery, the 3rd and 7th day after the surgery respectively.Calculate the difference(ΔX) between the score obtained before surgery and 3 or 7 days after the surgery (there are both positive and negative, we use the absolute value), with this difference( ΔX) divided by the standard deviation（SD）of the difference of the normal population, that is ΔX / SD and it is the Z score.If a patient has two or more than two of the absolute value of Z scores ≥1.96, the postoperative cognition dysfunction(POCD) is exist.

  1 day Before surgery,the 3rd,7th day after the surgery.

Secondary Outcomes (4)

• endothelial injury levels

  1 day Before surgery,the 1st, 2nd, 3rd,7th day after the surgery.

• Blood-brain barrier permeability

  1 day Before surgery,the 1st, 2nd, 3rd,7th day after the surgery.

• The serum concentrations of BDNF

  1 day Before surgery,the 1st, 2nd, 3rd,7th day after the surgery.

• Inflammatory factor

  1 day Before surgery,the 1st, 2nd, 3rd,7th day after the surgery.

Study Arms (2)

Dexmedetomidine

EXPERIMENTAL

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.

Drug: Dexmedetomidine

Controlled

PLACEBO COMPARATOR

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.

Drug: Saline

Interventions

Dexmedetomidine 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.

Dexmedetomidine

Saline 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.

Controlled

Eligibility Criteria

• Age: 65 Years - 90 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Older Adult (65+)

You may qualify if:

• Written informed consent;
• Patients undergoing selective major gastrointestinal surgery with laparoscope and general anesthesia;
• Age 65-90 yrs;
• Anesthesia Society of American (ASA) Scale II\~IV;
• Anticipated surgery time 2-6 hrs;

You may not qualify if:

• Dementia patients（Mini-mental state examination\< 20）
• Factors existed that affect cognition assessment such as language,visual,and auditory dysfunction；
• Unstable metal status and mental disease；
• A hematocrit value less than 28%in perioperative period;
• Patients with abnormal preoperative inflammatory indicators（Higher white blood cell and C-reactive protein);
• Patients undergoing cardiac and neural surgery;
• Parkinson's Disease；
• Sure or suspected abuse of analgesic and sedation drug.

Sponsors & Collaborators

• The First Affiliated Hospital of Anhui Medical University: lead
• Hangzhou Cancer Hospital: collaborator

Study Sites (2)

The First Affiliated Hospital of Anhui Medical University

Hefei, Anhui, China

Location

Hangzhou cancer hospital

Hangzhou, Zhejiang, China

Location

MeSH Terms

Conditions

Postoperative Cognitive Complications

Interventions

Dexmedetomidine; Sodium Chloride

Condition Hierarchy (Ancestors)

Postoperative Complications; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Cognitive Dysfunction; Cognition Disorders; Neurocognitive Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Chlorides; Hydrochloric Acid; Chlorine Compounds; Inorganic Chemicals; Sodium Compounds

Study Officials

• Xinqi Cheng, PhD

  The First Affiliated Hospital of Anhui Medical University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 13, 2018
• First Posted: August 21, 2018
• Study Start: July 1, 2019
• Primary Completion: October 30, 2020
• Study Completion: October 31, 2020
• Last Updated: February 10, 2021

Record last verified: 2019-09

Locations

CN (2)