Endothelial Injury Mechanism in Elderly Patients Undergoing Major Surgery

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

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.

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.