C-reactive Protein，Homocysteine，Postoperative Delirium

Postoperative Delirium Clinical Trial

Official title:

C-reactive Protein and Homocysteine and Their Interaction Contribute to Postoperative Delirium

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT05164965
• Other study ID #: dsyy007
• Status: Not yet recruiting
• Start date: January 10, 2022
• Est. completion date: December 30, 2023

Study information

• Verified date: December 2021
• Source: Shanghai 10th People's Hospital
• Contact: Yuan Shen, MD, PhD
• Phone: 2166303649
• Email: kmshy[@]tongji.edu.cn
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

The aim of this study is to evaluate how C-reactive protein (CRP) and homocysteine and their interaction contribute to postoperative delirium, based on our previous finding on the interactions of CRP, homocysteine and postoperative delirium.

Description:

Postoperative delirium is a common complication of patients who undergo major surgery. It is frequently accompanied by adverse outcomes like Alzheimer's disease, high risk of postoperative complications and poor long-term outcomes, but its pathogenesis and biomarkers remain undetermined. Neuroinflammation is emerging as a popular hypothesis of developing postoperative delirium, particularly via microglial activation and increased pro-inflammatory cytokines in the brain. However, not every patient with surgery-induced inflammation develops postoperative delirium. Thus, inflammation alone may be insufficient to explain postoperative delirium. Patients who develop postoperative delirium may have other changes (predisposing factors) that exacerbate surgery-induced inflammation (precipitating factor), leading to neuronal dysfunction.

A potential predisposing factor is hyperhomocysteine, a pathogenesis implicated in cardiovascular and Alzheimer's disease. Previous studies had indicated that preoperative hyperhomocysteine may be related to postoperative delirium, but the findings are conflicting. More importantly, the interaction between inflammation and hyperhomocysteine remains unknown, which may contribute more to postoperative delirium than the inflammation alone or hyperhomocysteine alone.

Thus, this study is a prospective observational cohort study to evaluate the interaction between CRP and hyperhomocysteine and their contribution to postoperative delirium. Patients scheduled for orthopedic surgeries will be included. Written informed consent will be obtained from all the patients.

Preoperative assessments：Participants recruited will receive preoperative assessments one day before the scheduled surgery by two well-trained researchers. The assessments include demographic characteristics (e.g., age, sex, education, marital status )，age-adjusted Charlson comorbidity index (ACCI) , cognitive function assessments (mini-mental state examination [MMSE] and Confusion Assessment Method [CAM]). And similarly venous blood samples of patient will be collected for homocysteine and C-reactive protein measurements.

Outcome measurement： Postoperative delirium will be assessed for the first, second and third day after surgery (twice daily, in the morning and afternoon respectively) using the CAM and CAM-Severity (CAM-S) long-form by two trained assessors. And venous blood samples of patients will be collected after the anesthesia/surgery for C-reactive protein measurements.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 150
• Est. completion date: December 30, 2023
• Est. primary completion date: December 30, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 60 Years and older

Eligibility

Inclusion Criteria:

1. were 60 years old or older

2. had a normal cognitive function at the time of enrollment, evidenced by a mini-mental state examination (MMSE) score above an education-adjusted threshold (18 for individuals with no school education, 20 for 1-6 years of education, or 24 for 7 or more years of education 27)

3. spoke Mandarin Chinese

4. were able to provide informed consent

5. scheduled for orthopaedic surgeries

Exclusion Criteria:

1. pre-existing delirium assessed according to the Confusion Assessment Method (CAM) algorithm;

2. prior neurologic diseases (Parkinson's disease, multiple sclerosis or stroke) according to the International Statistical Classification of Diseases and Related Health Problems 10th Revision (ICD-10);

3. history of mental disorders, e.g., major depressive disorder and schizophrenia, according to the Diagnostic and Statistical Manual of Mental Disorders, 4th edition (DSM-IV);

4. unwillingness to comply with the assessments.

Related Conditions & MeSH terms

• Delirium
• Postoperative Delirium

Locations

Country	Name	City	State
China	Shanghai Tenth People's Hospital	Shanghai	Shanghai

Sponsors (2)

Lead Sponsor	Collaborator
Shanghai 10th People's Hospital	Tongji Hospital

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Pain Scores	Patient reported pain assessments would be performed using the Visual Analogue Scale (VAS), which ranging from 0 (without pain) to 10 (extremely painful) scores. Patients would be requested to report pain scores when they were resting and moving during 1-3 days after surgery, once daily. Both the worst score and average score over time would be reported.	3 days after surgery
Other	Sleep difficulty	Patients self-reported sleep difficulty (including difficulty falling asleep, difficulty waking up and falling back asleep, waking up too early in the morning and sleepiness during the day) would be recorded for further analysis. Patients would be requested to report whether such sleep difficulty is newly emerging or re-emerging during 1-3 days after surgery, once daily. The rate of newly emerging sleep disorder would be report.	3 days after surgery
Primary	Incidence of postoperative delirium	Incidence of postoperative delirium on postoperative day 1, 2 and 3 will be defined according to the confusion assessment methods (CAM).	3 days after surgery
Secondary	Severity of postoperative delirium	Severity of postoperative delirium on postoperative day 1, 2 and 3 will be defined according to he Confusion Assessment Method based delirium severity evaluation tool (CAM-S).The sum score of CAM-S ranges from 0 (no) to 19 (most severe).	3 days after surgery