Endothelial Injury Mechanism in Elderly Patients Undergoing Major Surgery

Endothelial Dysfunction Clinical Trial

Official title:

Endothelial Injury Mechanism of Cognitive Decline and Intervention Study in Elderly Patients Undergoing Major Surgery

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03639896
• Other study ID #: 7742
• Status: Completed
• Phase: Phase 4
• Start date: July 1, 2019
• Est. completion date: October 31, 2020

Study information

• Verified date: September 2019
• Source: The First Affiliated Hospital of Anhui Medical University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 464
• Est. completion date: October 31, 2020
• Est. primary completion date: October 30, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 65 Years to 90 Years

Eligibility

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.

Related Conditions & MeSH terms

• Blood Brain Barrier Defect
• Cognitive Dysfunction
• Endothelial Dysfunction
• Postoperative Cognitive Dysfunction

Intervention

Drug:
• 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.
• 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.

Locations

Country	Name	City	State
China	Hangzhou cancer hospital	Hangzhou	Zhejiang
China	The First Affiliated Hospital of Anhui Medical University	Hefei	Anhui

Sponsors (2)

Lead Sponsor	Collaborator
The First Affiliated Hospital of Anhui Medical University	Hangzhou Cancer Hospital

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.
Primary	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(?X) 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( ?X) divided by the standard deviation(SD)of the difference of the normal population, that is ?X / 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	endothelial injury levels	Plasma of patients was collected to test heparan sulphate and syndecan-1.	1 day Before surgery,the 1st, 2nd, 3rd,7th day after the surgery.
Secondary	Blood-brain barrier permeability	Plasma of patients was collected to test S100B level	1 day Before surgery,the 1st, 2nd, 3rd,7th day after the surgery.
Secondary	The serum concentrations of BDNF	Serum level of brain-derived neurotrophic factor (BDNF) was measured.	1 day Before surgery,the 1st, 2nd, 3rd,7th day after the surgery.
Secondary	Inflammatory factor	Plasma of patients was collected to test cytokines IL-2, IL-6, TNF-a and VEGF level.	1 day Before surgery,the 1st, 2nd, 3rd,7th day after the surgery.