Dynamics of microRNA Expression and Systemic Inflammatory Response in POCD After Cardiac Surgery

NCT ID: NCT07231731

Last Updated: 2025-11-19

Basic Information

• Recruitment Status: COMPLETED
• Total Enrollment: 48 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2022-05-31
• Study Completion Date: 2023-10-26

Brief Summary

Postoperative cognitive decline (POCD) is one of the most common complications after cardiac surgery. It is characterized by impaired memory, attention, and executive functions and can have long-term consequences. The goal of this observational study was to investigate the mechanisms of cognitive decline after cardiac surgery and potential biomarkers that could aid in the diagnosis, prevention, and treatment of POCD. The investigators focused on the role of microRNAs (miRNAs) and systemic inflammatory response to surgery, extracorporeal circulation, and anesthesia as potential factors involved in the development of the neuroinflammatory response and subsequent POCD. The main question this study aims to answer is whether perioperative miRNA 151-5p expression is associated with POCD after surgery. The second aim is to examine the association between miRNA-151-5p and systemic inflammation. The investigators measured circulating miRNA-151-5p levels and plasma levels of inflammatory biomarkers in patients undergoing surgical myocardial revascularization. To assess cognitive function, participants completed the Montreal Cognitive Assessment (MoCA Test). Changes in the measured values of miRNA-151-5p expression and inflammatory markers, as well as changes in cognitive status after surgery, were assessed in relation to the preoperative state.

Detailed Description

Surgical myocardial revascularization is a procedure used in patients with ischemic heart disease to bypass atherosclerotic narrowings or blockages of the coronary arteries using an arterial or venous graft (Coronary Artery Bypass Grafting - CABG). One of the most common complications after cardiac surgery is postoperative cognitive decline (POCD). It is characterized by impaired memory, attention, and executive functions and can have long-term consequences, such as delayed physical therapy and mobilization, prolonged stay in the intensive care unit and hospital, more frequent discharge to nursing homes, reduced quality of life, and increased mortality.

The causes of POCD are multifactorial. The systemic inflammatory response to surgery, extracorporeal circulation, and anesthesia is considered a factor in the development of the neuroinflammatory response and subsequent POCD. Neuroinflammation can cause dysfunction or death of brain cells and damage to the blood-brain barrier, leading to an increase in the level of biochemical markers of brain injury in the blood. Studies indicate that numerous microRNAs (miRNAs) play a role in controlling the inflammatory response. MiRNAs are small, endogenous, non-coding RNA molecules, typically 18-25 nucleotides long, that regulate gene expression at the post-transcriptional level. They are central mediators of cellular proliferation, differentiation, and apoptosis. MiRNA levels in tissues and peripheral blood are similar, and circulating miRNAs are stable and suitable for measurement. Specific miRNAs (miRNA 151-5p, 505, 499, 625, and others) may be potential early biomarkers of brain damage after a mild traumatic brain injury. Anesthesia and surgery also, through complex mechanisms, can cause changes in brain cells that can lead to the release of specific miRNAs, and these miRNAs can be detected in blood and various biological fluids.

Hypothesis: Higher levels of perioperative miRNA-151-5p expression are associated with the systemic inflammatory response and with the development of POCD.

Aim of this study is:

1. To investigate the association between miRNA-151-5p expression levels and biochemical parameters of systemic inflammation, as well as the association of both with cognitive status in patient undergoing CABG surgery.

2. To investigate the association between patients' demographic and clinical characteristics and miRNA-151-5p expression levels, the level of biochemical parameters of systemic inflammation, and patients' cognitive status.

Research plan:

The research was carried out at the Clinical Hospital Centre Osijek. Respecting the inclusion and exclusion criteria for participation in the study, the research included patients aged 65 to 80 years who, according to the American Society of Anesthesiologists (ASA) classification, are classified into groups III and IV, and who are undergoing CABG surgery with the use of extracorporeal circulation. Surgeries were performed according to the standard protocol for balanced anesthesia, cardiac surgery, and extracorporeal circulation. All participants underwent the same anesthetic procedure and anesthesia based on midazolam, propofol, sufentanyl, rocuronium and sevoflurane. The depth of anesthesia was monitored using Patient State Index (PSI). All surgeries were performed using extracorporeal circulation with the maintenance of normothermia (36 °C).

Blood samples for determination of levels of cholinesterase, interleukin-6, protein S100B, miRNA-151-5p expression and routine laboratory parameters (complete blood count, levels of troponin I, C-reactive protein, procalcitonin, glucose, urea, creatinine, aspartate aminotransferase, alanine aminotransferase, gamma-glutamyl transferase, total bilirubin, albumin, electrolytes, lactate, coagulation tests, and arterial blood gas analysis) were taken at three time points: before surgery prior to induction of anesthesia, immediately after the procedure upon admission to the intensive care unit, and 48 hours after the surgical procedure.

Cognitive function testing was performed the day before surgery and postoperatively, once daily every day until the 6th postoperative day. The investigators used a validated scoring scale for assessing cognitive functions, the Montreal Cognitive Assessment - MoCA Test. Demographic and clinical data were recorded for all subjects. Subjects were followed up 7 days.

Conditions

Biomarkers; Coronary Artery Bypass Surgery; Interleukin-6; MicroRNAs; Postoperative Cognitive Complications; Systemic Inflammatory Response Syndrome

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: PROSPECTIVE

Study Groups

Coronary Artery Bypass Graft (CABG) group

The study include a cohort of patients, between the ages of 65 and 80, who undergo coronary artery bypass graft surgery to treat coronary artery disease, receiving 2 or more coronary artery bypass grafts with the use of extracorporeal circulation.

No interventions assigned to this group

Eligibility Criteria

Inclusion Criteria

• patients undergoing coronary artery bypass graft surgery to treat coronary artery disease
• two or more coronary bypass surgery with the use of extracorporeal circulation
• patients between the ages of 65 and 80
• patients according to the classification of the American Society of Anesthesiologists (ASA) classified in groups III and IV
• patients who agreed to participate in the research and signed an informed consent

Exclusion Criteria

• patients with communication difficulties (severe visual, hearing and speech impairment)
• illiterate patients
• patients with a history of dementia, schizophrenia, Parkinson's disease, Alzheimer's disease, alcoholism
• patients with previously known liver failure of any grade according to the Child-Pough classification
• patients with previously known renal failure greater than grade 2
• patients taking immunosuppressive, corticosteroid and anticholinergic therapy
• intraoperatively used cell-saver and/or hemofilter
• patients in whom the planned procedure is not performed
• patients in whom it is not possible to assess cognitive functions postoperatively (patients sedated due to intra- or postoperative surgical complications)

• Minimum Eligible Age: 65 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Josip Juraj Strossmayer University of Osijek

OTHER

Sponsor Role: collaborator

Osijek University Hospital

OTHER

Sponsor Role: lead

Responsible Party

Visnja Ikic, MD

Doctor of medicine, Specialist in anaesthesiology, reanimatology and intensive care medicine, Subspecialist in intensive care medicine

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Slavica Kvolik, Professor

Role: STUDY_CHAIR

University Hospital Osijek

Locations

University Hospital Osijek

Osijek, , Croatia

Countries

Croatia

References

van Harten AE, Scheeren TW, Absalom AR. A review of postoperative cognitive dysfunction and neuroinflammation associated with cardiac surgery and anaesthesia. Anaesthesia. 2012 Mar;67(3):280-93. doi: 10.1111/j.1365-2044.2011.07008.x.

Reference Type: BACKGROUND

PMID: 22321085 (View on PubMed)

Kok WF, Koerts J, Tucha O, Scheeren TW, Absalom AR. Neuronal damage biomarkers in the identification of patients at risk of long-term postoperative cognitive dysfunction after cardiac surgery. Anaesthesia. 2017 Mar;72(3):359-369. doi: 10.1111/anae.13712. Epub 2016 Dec 17.

Reference Type: BACKGROUND

PMID: 27987229 (View on PubMed)

Berger M, Terrando N, Smith SK, Browndyke JN, Newman MF, Mathew JP. Neurocognitive Function after Cardiac Surgery: From Phenotypes to Mechanisms. Anesthesiology. 2018 Oct;129(4):829-851. doi: 10.1097/ALN.0000000000002194.

Reference Type: BACKGROUND

PMID: 29621031 (View on PubMed)

Greaves D, Psaltis PJ, Ross TJ, Davis D, Smith AE, Boord MS, Keage HAD. Cognitive outcomes following coronary artery bypass grafting: A systematic review and meta-analysis of 91,829 patients. Int J Cardiol. 2019 Aug 15;289:43-49. doi: 10.1016/j.ijcard.2019.04.065. Epub 2019 Apr 24.

Reference Type: BACKGROUND

PMID: 31078353 (View on PubMed)

Kapoor MC. Neurological dysfunction after cardiac surgery and cardiac intensive care admission: A narrative review part 1: The problem; nomenclature; delirium and postoperative neurocognitive disorder; and the role of cardiac surgery and anesthesia. Ann Card Anaesth. 2020 Oct-Dec;23(4):383-390. doi: 10.4103/aca.ACA_138_19.

Reference Type: BACKGROUND

PMID: 33109792 (View on PubMed)

Polito F, Fama F, Oteri R, Raffa G, Vita G, Conti A, Daniele S, Macaione V, Passalacqua M, Cardali S, Di Giorgio RM, Gioffre M, Angileri FF, Germano A, Aguennouz M. Circulating miRNAs expression as potential biomarkers of mild traumatic brain injury. Mol Biol Rep. 2020 Apr;47(4):2941-2949. doi: 10.1007/s11033-020-05386-7. Epub 2020 Mar 26.

Reference Type: BACKGROUND

PMID: 32219772 (View on PubMed)

Pozniak T, Shcharbin D, Bryszewska M. Circulating microRNAs in Medicine. Int J Mol Sci. 2022 Apr 3;23(7):3996. doi: 10.3390/ijms23073996.

Reference Type: BACKGROUND

PMID: 35409354 (View on PubMed)

Related Links

https://www.mocatest.org

MoCA - Cognitive Assessment \[Internet\]. \[cited 2022 Feb 9\]. MoCA - Cognitive Assessment. Available from: https://www.mocatest.org/.

Other Identifiers

microRNA-POCD

Identifier Type: -

Identifier Source: org_study_id