Perioperative Sepsis. An Epigenetic Perspective

This study is a single-center, prospective, observational cohort study designed to investigate the pathophysiological impact of perioperative sepsis on inflammatory, cardiac, coagulation, and microRNA profiles in adult patients undergoing major abdominal surgery. The study is conducted at a university hospital within the Department of Intensive Care and is strictly observational, with no modification to standard perioperative clinical management.

Major abdominal surgery is associated with a significant inflammatory response and carries a substantial risk of postoperative complications, including sepsis. Perioperative sepsis is known to contribute to organ dysfunction, particularly affecting the cardiovascular and coagulation systems; however, the underlying biological and molecular mechanisms remain incompletely understood. In particular, the role of circulating microRNAs as early biomarkers and potential mediators of sepsis-related organ dysfunction in the perioperative setting has not been fully elucidated. This study aims to characterize the early biological, echocardiographic, and molecular changes associated with perioperative sepsis.

A total of 40 adult patients (≥18 years) undergoing elective or emergency major abdominal surgery are enrolled after providing written informed consent. All participants must be hemodynamically stable preoperatively and have available biological samples obtained in the preoperative period and within the first 24 hours after surgery. Patients are followed during the perioperative period only, with no long-term follow-up beyond 24 hours postoperatively.

Following surgery, patients are classified into two cohorts based on international sepsis definitions and Sequential Organ Failure Assessment (SOFA) score criteria. The septic cohort consists of patients with confirmed or suspected infection associated with an increase in SOFA score of at least 2 points from baseline. The non-septic cohort includes patients undergoing major abdominal surgery without clinical, biological, or organ dysfunction evidence of sepsis. Allocation to study groups is non-randomized and determined solely by sepsis criteria.

Biological assessments are performed preoperatively and within 24 hours postoperatively and include markers of systemic inflammation, coagulation, organ function, and cardiac injury. These include presepsine, C-reactive protein, fibrinogen, liver enzymes (AST, ALT), renal function markers (creatinine, urea), creatine kinase and CK-MB, NT-proBNP, and cardiac troponin. Cardiac function is further evaluated using transthoracic echocardiography to assess sepsis-related myocardial dysfunction.

In parallel, peripheral blood samples are collected for molecular analysis of selected microRNAs implicated in inflammation, immune regulation, coagulation, and cardiac injury. The microRNAs analyzed include miR-146a, miR-155, miR-223, miR-150, miR-21, miR-133a, and miR-27a. MicroRNA expression levels are evaluated preoperatively and within the first 24 hours after surgery.

The primary objective is to assess the impact of perioperative sepsis on inflammatory, cardiac, coagulation, and microRNA profiles. Secondary objectives include comparisons of these biomarkers between septic and non-septic patients, correlations between SOFA score and biological, echocardiographic, and molecular parameters, and exploration of associations between microRNA expression patterns and the severity of organ dysfunction. An additional exploratory objective is to evaluate the potential prognostic value of selected microRNAs as early biomarkers of postoperative sepsis.

The study is conducted in accordance with the Declaration of Helsinki and applicable national regulations. No study-related interventions are performed, and all data collection is based on routine clinical assessments and additional laboratory analyses performed on collected samples.

• The impact of abdominal sepsis on the postoperative left ventricular function. Comparison of the means of left ventricular ejection fraction (EFLV) measurements across groups. [Time frame: 2 days before surgery until day 1 after surgery]
• The impact of abdominal sepsis on the postoperative E/A and E/e´ ratio. Comparison of the means of the E/A and E/e´ ratios across groups. [Time frame: 2 days before surgery until day 1 after surgery]
• The impact of the abdominal sepsis on the postoperative velocity-time integral (VTI). Comparison of the means of the VTI across groups. [Time frame: 2 days before surgery until day 1 after surgery]
• The impact of abdominal sepsis on the postoperative right ventricle (RV) to right atrial (RA) gradient. Comparison of the means of the RV-to-RA gradient across groups. [Time frame: 2 days before surgery until day 1 after surgery]
• The impact of abdominal sepsis on the postoperative tricuspid annular plane systolic excursion (TAPSE). Comparison of the means of the TAPSE across groups. [Time frame: 2 days before surgery until day 1 after surgery]
• The impact of abdominal sepsis on the postoperative diameter of the inferior vena cava (IVC). Comparison of the means of IVC diameter across groups. [Time frame: 2 days before surgery until day 1 after surgery]
• The impact of abdominal sepsis on the postoperative systolic tissue velocity (s´) wave of the right ventricular free wall. Comparison of the means of the s´ wave across groups. [Time frame: 2 days before surgery until day 1 after surgery]
• The impact of abdominal sepsis on the postoperative dynamics of cardiac biomarkers and presepsine. Comparison of the means of cardiac biomarkers and presepsine across groups. [Time frame: 2 days before surgery until day 1 after surgery]
• The impact of abdominal sepsis on liver function. Comparison of the means of liver enzymes across groups. [Time frame: 2 days before surgery until day 1 after surgery]
• The impact of abdominal sepsis on the postoperative inflammation and renal function. Comparison of the means of the biomarkers for inflammation and renal function across groups. [Time frame: 2 days before surgery and day 1 after surgery]