Inflammatory and Vasoactive Mediator Profiles and Pathogen Characterization During Heart Valve Replacement Surgery
Trial Snapshot
- Phase
- Not Applicable
- Status
- Completed
- Sponsor
- Jena University Hospital
- Enrollment
- 40
- Locations
- 1
- Primary Endpoint
- Area under the plasma concentration versus time curve (AUC) of C-reactive Protein (CRP)
Study Overview
Brief Summary
The study aims at the comparative examination of pre-, intra- and post-operative release profiles of inflammatory and vasoactive mediators in patients undergoing heart valve surgery under cardiopulmonary bypass (CPB) due to either infectious endocarditis or degenerative valvular heart disease. Specific attention will focus on the distinction between mediator release associated with infection and that resulting from CPB. Concomitantly identification and characterization of infectious pathogens in the circulation and in valvular samples will be carried out, together with the search for resistance-coding transcripts.
Detailed Description
Exaggerated release of inflammatory mediators and endogenous vasoactive substances resulting from the coincident infection and surgical stress plays a role in post-operative organ failure and altered immune defense, thus contributing to unfavorable post-operative outcome.
Cardiopulmonary bypass (CPB) itself, even in the absence of IE, has been shown to modify cytokine and vasoactive mediator release and may cause organ failure. Tracing of release profiles of inflammatory cytokines and vasoactive mediators and their correlation with postoperative organ dysfunction in cardiac surgery for IE or non-IE patients aims at the assessment of the prognostic validity of these biomarkers and the evaluation of measures for their pro-active clearance during the surgical intervention.
Induction of inflammatory mediators and their temporal release profile may vary depending on the involved pathogens, which cannot be always identified by conventional techniques (blood culture). Since it is conceivable that identification of the involved pathogen could explain differences in cytokine secretory patterns in IE, use of advanced molecular technologies (NGS) will support the clarification of such relations. Analysis of transcripts encoding inflammatory and vasoactive mediators in blood cells will enable the surveillance of temporal oscillations in their profiles during the observation time frame. Transcriptome analysis of identified putative pathogens can also disclose features of antibiotic resistance.
Study Design
- Study Type
- Observational
- Observational Model
- Case Control
- Time Perspective
- Cross Sectional
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •signed informed consent
- •age > 18
- •confirmed diagnosis of infective endocarditis or valvular heart disease
- •scheduled surgical Intervention with CPB use
Exclusion Criteria
- •glucocorticoid dosage above Cushing threshold
- •severe neutropenia (below 1000/mm3)
- •immunosuppression or immunomodulatory therapy
- •pregnancy
Outcomes
Primary Outcomes
Area under the plasma concentration versus time curve (AUC) of C-reactive Protein (CRP)
Time Frame: 24 h before surgery - connection/disconnection of CPB - 24 and 48 h post-surgery
Plasma Levels of CRP over time
Area under the plasma concentration versus time curve (AUC) of Interleukin (IL) 10
Time Frame: 24 h before surgery - connection/disconnection of CPB - 24 and 48 h post-surgery
Plasma Levels of IL 10 over time
Area under the plasma concentration versus time curve (AUC) of Endothelin 1
Time Frame: 24 h before surgery - connection/disconnection of CPB - 24 and 48 h post-surgery
Plasma Levels of Endothelin 1 over time
Area under the plasma concentration versus time curve (AUC) of Tumor Necrosis Factor (TNF) alpha
Time Frame: 24 h before surgery - connection/disconnection of CPB - 24 and 48 h post-surgery
Plasma Levels of TNF alpha over time
Area under the plasma concentration versus time curve (AUC) of Interleukin (IL) 1beta
Time Frame: 24 h before surgery - connection/disconnection of CPB - 24 and 48 h post-surgery
Plasma Levels of IL 1beta over time
Area under the plasma concentration versus time curve (AUC) of Procalcitonin
Time Frame: 24 h before surgery - connection/disconnection of CPB - 24 and 48 h post-surgery
Plasma levels of Procalcitonin over time
Area under the plasma concentration versus time curve (AUC) of Interleukin (IL) 6
Time Frame: 24 h before surgery - connection/disconnection of CPB - 24 and 48 h post-surgery
Plasma Levels of IL 6 over time
Area under the plasma concentration versus time curve (AUC) of Interleukin (IL) 18
Time Frame: 24 h before surgery - connection/disconnection of CPB - 24 and 48 h post-surgery
Plasma Levels of IL 18 over time
Secondary Outcomes
- Area under the plasma concentration versus time curve (AUC) of pro-Atrial natriuretic peptide(24 h before surgery - connection/disconnection of CPB - 24 and 48 h post-surgery)
- Area under the plasma concentration versus time curve (AUC) of pro-Adrenomedullin(24 h before surgery - connection/disconnection of CPB - 24 and 48 h post-surgery)
- SOFA Score(24 h before and 24 and 48 h after surgical intervention)
- Concomitant medication(During and 48 h upon completion of surgical intervention)
- Renal replacement therapy(Over 7 days following surgery)
- Area under the plasma concentration versus time curve (AUC) of pro-Arginine vasopressin(24 h before surgery - connection/disconnection of CPB - 24 and 48 h post-surgery)
- In-hospital mortality(30 days after surgery)