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

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

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 .

Study Overview

• Status: Unknown
• Conditions: Postoperative Delirium; Elective Non-Cardiac Surgery
• Intervention / Treatment: Diagnostic test: Neuropsychological tests

Detailed Description

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 .

• Study Type: Observational
• Enrollment (Anticipated): 400

Contacts and Locations

Study Locations

• China
  • Jiangsu
    • Xuzhou, Jiangsu, China, 221000
      • Recruiting
      • Junli Cao

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 58 years to 88 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

Patients aged ≥60 years undergoing elective non-cardiac major surgery under general anesthesia were investigated.

Description

Inclusion Criteria:

1. Patients undergoing selective major noncardiac surgery and general anesthesia;
2. Age 60-90 yrs;
3. Anesthesia Society of American (ASA) Scale II~III;
4. Anticipated surgery time 2-6 hrs
5. Written informed consent;

Exclusion Criteria:

1. decline to participate
2. Dementia patients（Mini-mental state examination< 20）
3. Factors existed that affect cognition assessment such as language,visual,and auditory dysfunction.

Study Plan

How is the study designed?

Design Details

• Observational Models: Case-Control
• Time Perspectives: Prospective

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
POD group; POD group refers to the patients who were diagnosed to be delirious by the Confusion Assessment Method.	Diagnostic test: Neuropsychological tests; 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.
Non-POD group; Non-POD refered to the patients who did not become delirious by the Confusion Assessment Method.	Diagnostic test: Neuropsychological tests; 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.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Xuzhou Medical University

Study record dates

Study Major Dates

• Study Start (Actual): April 1, 2019
• Primary Completion (Anticipated): April 1, 2020
• Study Completion (Anticipated): April 1, 2020

Study Registration Dates

• First Submitted: April 5, 2019
• First Submitted That Met QC Criteria: April 11, 2019
• First Posted (Actual): April 16, 2019

Study Record Updates

• Last Update Posted (Actual): April 16, 2019
• Last Update Submitted That Met QC Criteria: April 11, 2019
• Last Verified: April 1, 2019

More Information

Terms related to this study

• Keywords: delirium; endothelial dysfunction; blood biomakers; blood brain barrier (BBB)
• Additional Relevant MeSH Terms: Mental Disorders; Nervous System Diseases; Neurologic Manifestations; Confusion; Neurobehavioral Manifestations; Neurocognitive Disorders; Delirium
• Other Study ID Numbers: XYFY2018-KL091-01

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No