Correlation Between Blood Biomarkers and Postoperative Delirium in Elective Non-Cardiac Surgery.

Study Overview
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Brief Summary
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More than 20% of patients over 60 years old develop postoperative delirium following non-cardiac surgery . Delirium increases morbidity and mortality , and may lead to long-term cognitive impairment . The underlying mechanisms behind delirium are not understood , endothelial dysfunction and disruption of the blood brain barrier (BBB ) caused by perioperative systemic inflammation may play a important role in the development of delirium . This study intends to evaluate the relationship between neuroinflammation and postoperative delirium in elderly non-cardiac surgery patients . The results of the study are to identify risk factors and explore the biomarkers most closely linked to each step of the proposed pathway .

Detailed Description
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The investigators do the neuropsychological tests , Mini-Mental score examination (MMSE ) , Charlson Comorbidity Index (CCI ) , Quality of Recovery Score - 40 (QoR-40 ) 1 day before the surgery（baseline ) . Serum of the patients was collected before operation and at POD1 , and then detect the concentration change of biomarkers of endothelial dysfunction , blood brain barrier disruption and neuronal injury . Also , the patients were interviewed once before discharge from PACU and twice on postoperative days 1-3 by the Confusion Assessment Method and then divided them into POD and non-POD groups . Meanwhile , the severity of pain (Numerical Rating Scale（NRS )) was evaluated at the same time and QoR-40 at 1 day after surgery .

Official Title
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The Association Between Blood Biomarkers and Postoperative Delirium in Elective Non-Cardiac Surgery Under General Anesthsia.

Conditions
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Postoperative Delirium, Elective Non-Cardiac Surgery

Intervention / Treatment
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* Diagnostic Test: Neuropsychological tests


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients undergoing selective major noncardiac surgery and general anesthesia; Age 60-90 yrs; Anesthesia Society of American (ASA) Scale II III; Anticipated surgery time 2-6 hrs Written informed consent; Exclusion Criteria: decline to participate Dementia patients（Mini-mental state examination< 20） Factors existed that affect cognition assessment such as language,visual,and auditory dysfunction.

Ages Eligible for Study
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Minimum Age: 60 Years
Maximum Age: 90 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| POD group<br>POD group refers to the patients who were diagnosed to be delirious by the Confusion Assessment Method. | Diagnostic Test: Neuropsychological tests<br>* The investigators do the neuropsychological tests, Mini-Mental score examination (MMSE),Charlson Comorbidity Index(CCI)，Quality of Recovery Score - 40 (QoR-40),CAGE Alcoholism Questionnaire,blood albumin、hemoglobin content、ALT、AST、BUN、Cr、1 day before the surgery（baseline);serum biomarkers of endothelial dysfunction，blood brain barrier disruption and neuronal injury to be measured at 2 time points,1 day before the surgery（baseline）and postoperative day 1； Confusion Assessment Method（CAM)，Numerical Rating Scale（NRS）once before discharge from PACU and 1、2、3 days after surgery twice a day； QoR-40 1 day after surgery.<br>|
| Non-POD group<br>Non-POD refered to the patients who did not become delirious by the Confusion Assessment Method. | Diagnostic Test: Neuropsychological tests<br>* The investigators do the neuropsychological tests, Mini-Mental score examination (MMSE),Charlson Comorbidity Index(CCI)，Quality of Recovery Score - 40 (QoR-40),CAGE Alcoholism Questionnaire,blood albumin、hemoglobin content、ALT、AST、BUN、Cr、1 day before the surgery（baseline);serum biomarkers of endothelial dysfunction，blood brain barrier disruption and neuronal injury to be measured at 2 time points,1 day before the surgery（baseline）and postoperative day 1； Confusion Assessment Method（CAM)，Numerical Rating Scale（NRS）once before discharge from PACU and 1、2、3 days after surgery twice a day； QoR-40 1 day after surgery.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| serum concentration change in biomarker of endothelial dysfunction | C-terminal endothelin-1 (CT-proET-1) to be measured at 2 time points | baseline, postoperative day 1 | 
| serum concentration change in biomarker of blood brain barrier disruption | caveolin-1 to be measured at 2 time points | baseline, postoperative day 1 | 
| serum concentration change in biomarker of neuronal injury | Neurofilament light (NfL) to be measured at 2 time points | baseline, postoperative day 1 | 
| The incidence of postoperative delirium | The patients were interviewed one day before the surgery and on postoperative days 1-3 by the Confusion Assessment Method and then divided them into POD and non-POD groups. | From day 0 to up to 3 days after the surgery | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Quality of Recovery Score - 40 (QoR-40) at baseline | Quality of recovery will be evaluated by Quality of Recovery 40 (QoR40),which assesses five dimensions of recovery (physical comfort,emotional state, physical independence , physiological support and pain ). Each item is rated on a five-point Likert scale: none of the time, some of the time, usually, most of the time, and all the time. The total score on the QoR40 ranges from 40 (poorest quality of recovery) to 200 (best quality of recovery). | 1 day before the surgery(baseline) | 
| Quality of Recovery Score - 40 (QoR-40) after surgry | Quality of recovery will be evaluated by Quality of Recovery 40 (QoR40),which assesses five dimensions of recovery (physical comfort,emotional state, physical independence , physiological support and pain ). Each item is rated on a five-point Likert scale: none of the time, some of the time, usually, most of the time, and all the time. The total score on the QoR40 ranges from 40 (poorest quality of recovery) to 200 (best quality of recovery). | 1 day after the surgery | 
| The severity of pain at baseline | Evaluate the severity using numerical rating scale（NRS）, where zero mean no pain and 10 the worst imaginable pain. | 1 day before the surgery(baseline) | 
| The severity of pain after surgry | Evaluate the severity using numerical rating scale（NRS）, where zero mean no pain and 10 the worst imaginable pain. | From day 0 to up to 3 days after the surgery | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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delirium, blood biomakers, endothelial dysfunction, blood brain barrier (BBB)