Perioperative Sepsis. An Epigenetic Perspective (PESE)

Impact of Perioperative Sepsis on Inflammatory, Cardiac, Coagulation, and microRNA Profiles in Patients Undergoing Major Abdominal Surgery

This single-center, prospective, observational study evaluates the impact of perioperative sepsis on inflammatory response, coagulation abnormalities, cardiac dysfunction, and microRNA expression in adult patients undergoing major abdominal surgery. Forty patients are enrolled and classified into septic and non-septic groups according to international sepsis definitions based on SOFA score criteria. Clinical, biochemical, echocardiographic, and molecular parameters, including selected microRNAs, are assessed preoperatively and within the first 24 hours postoperatively. The study aims to characterize pathophysiological differences associated with perioperative sepsis and to explore the potential prognostic value of microRNAs as early biomarkers of postoperative sepsis.

Study Overview

• Status: Recruiting
• Conditions: Sepsis Abdominal
• Intervention / Treatment: Diagnostic test: • Presepsin • C-reactive protein (CRP) • Fibrinogen • Aspartate aminotransferase (AST) • Alanine aminotransferase (ALT) • Creatinine • Urea • Creatine kinase (CK) • Creatine kinase-MB (CK-MB) • NT-pro

Detailed Description

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.

• Study Type: Observational
• Enrollment (Estimated): 40

Contacts and Locations

• Study Contact: Name: Sebastian I Isac, Assist. Prof.; Phone Number: 0040744543736; Email: sebastian.isac@umfcd.ro
• Study Contact Backup: Name: Buzatu Cristina; Phone Number: 0040727391477; Email: cristina.buzatu944@gmail.com

Study Locations

• Romania
  • Sector 2
    • Bucharest, Sector 2, Romania, 022328
      • Recruiting
      • Institutul Clinic Fundeni
      • Contact: Sebastian I Isac; Phone Number: 0040744543736; Email: sebastian.isac@umfcd.ro
      • Contact: Cristina Buzatu; Phone Number: 0040727391477; Email: cristina.buzatu944@gmail.com
      • Principal Investigator: Sebastian I Isac, Assist. Prof.
      • Sub-Investigator: Cristina Buzatu
      • Sub-Investigator: Gabriela Droc, Prof.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

The study population includes adult patients (≥18 years) undergoing elective or emergency major abdominal surgery at a single academic university hospital. Eligible patients must be hemodynamically stable in the preoperative period, able to provide written informed consent, and have biological samples available both before surgery and within 24 hours postoperatively. A total of 40 patients are prospectively enrolled and followed during the perioperative period only. The patients are devided into septic or non-septic.

Description

Inclusion Criteria:

• Age ≥18 years
• Undergoing major abdominal surgery (elective or emergency)
• Ability to provide written informed consent
• Availability of biological samples in the preoperative period and within 24 hours postoperatively
• Preoperative hemodynamic stability

Exclusion Criteria:

• Surgical reintervention within 3 months after the index procedure
• Multiple surgical procedures during the same hospitalization
• Active chronic infections (HIV, active viral hepatitis, tuberculosis)
• Autoimmune or systemic inflammatory diseases
• Chronic immunosuppressive therapy or long-term corticosteroid use
• Severe hepatic failure (Child-Pugh class C)
• End-stage renal disease requiring dialysis
• Severe pre-existing cardiac disease (NYHA class III-IV heart failure)
• Pregnancy
• Refusal or inability to provide informed consent

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Septic; Patients with confirmed or suspected infection associated with an increase in SOFA score ≥2 points from baseline during the perioperative period.	Diagnostic test: • Presepsin • C-reactive protein (CRP) • Fibrinogen • Aspartate aminotransferase (AST) • Alanine aminotransferase (ALT) • Creatinine • Urea • Creatine kinase (CK) • Creatine kinase-MB (CK-MB) • NT-pro; Study procedures are limited to the collection of clinical data, transthoracic echocardiography, and peripheral blood samples obtained preoperatively and within 24 hours postoperatively. Laboratory analyses include inflammatory markers (presepsin, C-reactive protein), coagulation parameters (fibrinogen), biochemical and organ function markers (AST, ALT, creatinine, urea), cardiac injury and function markers (creatine kinase, CK-MB, NT-proBNP, cardiac troponin), and peripheral blood microRNA expression (miR-146a, miR-155, miR-223, miR-150, miR-21, miR-133a, miR-27a). Patient classification into septic or non-septic cohorts is based solely on postoperative clinical assessment and SOFA score; Other Names: • Transthoracic echocardiography
Non-septic; Patients undergoing major abdominal surgery without clinical or biological evidence of sepsis.	Diagnostic test: • Presepsin • C-reactive protein (CRP) • Fibrinogen • Aspartate aminotransferase (AST) • Alanine aminotransferase (ALT) • Creatinine • Urea • Creatine kinase (CK) • Creatine kinase-MB (CK-MB) • NT-pro; Study procedures are limited to the collection of clinical data, transthoracic echocardiography, and peripheral blood samples obtained preoperatively and within 24 hours postoperatively. Laboratory analyses include inflammatory markers (presepsin, C-reactive protein), coagulation parameters (fibrinogen), biochemical and organ function markers (AST, ALT, creatinine, urea), cardiac injury and function markers (creatine kinase, CK-MB, NT-proBNP, cardiac troponin), and peripheral blood microRNA expression (miR-146a, miR-155, miR-223, miR-150, miR-21, miR-133a, miR-27a). Patient classification into septic or non-septic cohorts is based solely on postoperative clinical assessment and SOFA score; Other Names: • Transthoracic echocardiography

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The impact of abdominal sepsis on the microRNA profile. Comparison of the mean values of epigenetic biomarkers across groups	Assessment of miR-146a, miR-155, miR-223, miR-150, miR-21, miR-133a, miR-27a in plasma	2 days before surgery until day 1 after surgery

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The impact of abdominal sepsis on the postoperative left ventricular function. Comparison of the means of left ventricular ejection fraction (EFLV) measurements across groups.	Ultrasonographic assessment of the ejection fraction of the left ventricle (EFLV) in %	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.	Ultrasonographic assessment of the early (E) and atrial (A) waves of the left ventricle in m/s and their ratio, and the early diastolic mitral annular velocity (e´) and E/e´ ratio respectively	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.	Ultrasonographic assessment of the velocity-time integral in cm	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.	Ultrasonographic assessment of the RV to RA gradient in mmHg	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.	Ultrasonographic assessment of the tricuspid annular plane systolic excursion (TAPSE) in mm.	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.	Ultrasonographic assessment of the IVC diameter in mm.	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.	Ultrasonographic assessment of the s´ wave of the right ventricle free wall in cm/s.	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.	Assessment of cardiac biomarkers in plasma, such as highly sensitive troponine I (hsTnI) (pg/ml), NT-proBNP (pg/ml), procalcitonine (PCT) (pg/ml), and presepsine (pg/ml)- as a biomarker for sepsis	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.	Assessment of the aspartate aminotransferase (AST) (U/L), and alanine aminotransferase (ALT) (U/L),	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.	Assessment of the following markers in plasma: C-reactive protein (CRP) (mg/dl), Fibrinogen (mg/dl), Creatinine (mg/dl), blood urea nitrogen (BUN) (mg/dl)	2 days before surgery and day 1 after surgery

Collaborators and Investigators

• Sponsor: Carol Davila University of Medicine and Pharmacy
• Investigators: Study Director: Sebastian I Isac, Department of Anesthesia and Intensive Care I, Carol Davila University of Medicine and Pharmacy; Study Chair: Gabriela Droc, Prof., Department of Anesthesia and Intensive Care I, Carol Davila University of Medicine and Pharmacy

Study record dates

Study Major Dates

• Study Start (Actual): January 20, 2026
• Primary Completion (Estimated): March 30, 2026
• Study Completion (Estimated): April 10, 2026

Study Registration Dates

• First Submitted: February 2, 2026
• First Submitted That Met QC Criteria: February 24, 2026
• First Posted (Actual): March 2, 2026

Study Record Updates

• Last Update Posted (Actual): March 2, 2026
• Last Update Submitted That Met QC Criteria: February 24, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Keywords: echocardiography; epigenetics; perioperative sepsis; biochemical markers in sepsis
• Additional Relevant MeSH Terms: Infections; Intraabdominal Infections; Diagnostic Techniques and Procedures; Diagnosis; Diagnostic Imaging; Diagnostic Techniques, Cardiovascular; Heart Function Tests; Cardiac Imaging Techniques; Ultrasonography; Echocardiography
• Other Study ID Numbers: pese0004

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED
• IPD Plan Description: due confidential data sharing and explicit consent

Drug and device information, study documents

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