Differential Regulation of RAAS-axis in Patients Undergoing Cardiac Surgery

Study Overview
=================
Brief Summary
-----------------
This study investigates the question of whether there are differences in the plasma concentration of hormones of the RAAS-axis between patients undergoing on-pump cardiac surgery and those receiving off-pump surgery

Detailed Description
-----------------
In patients undergoing cardiac surgery, the occurrence of vasoplegia or vasoplegic shock is a common and sometimes very severe complication. Although there are multiple factors that may affect the incidence and severity of vasoplegia, it remains unclear which role the use of cardiopulmonary bypass may play in the pathogenesis of this complication. The heart normally pumps blood through the lungs where the blood primarily gets oxygenated. However, it is also known that pulmonary blood flow is also essential for the activation of various hormones, some of which are central to the regulation of vascular tension and blood pressure. If the pulmonary circulation is bypassed, as is the case in on-pump cardiac surgery, it is likely that the resulting differential activity of hormones may cause or contribute to the incidence of vasoplegia. This study aims to show whether cardiopulmonary bypass leads to the differential regulation of hormones of the renin-angiotensin-aldosterone-system which could explain why some patients suffer from vasoplegia or vasoplegic shock following such procedures.

Official Title
-----------------
Differences in Plasma Concentration of RAAS-axis Hormones in Patients Undergoing Cardiac Surgery With or Without Cardiopulmonary Bypass

Conditions
-----------------
Vasoplegia, Vasoplegic Shock

Intervention / Treatment
-----------------
* Procedure: on-pump surgery
* Procedure: off-pump surgery


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: adult patients undergoing on- or off-pump coronary artery bypass graft surgery written informed consent Exclusion Criteria: emergency surgery in the context of acute coronary syndrome ACE-inhibitor or Angiotensin 1 (AT1)-receptor-blocker intake that was not paused on the day of surgery Chronic kidney disease with estimated glomerular filtration rate (eGFR)<30ml/min/1.73m² Severe structural lung disease (asbestosis, silicosis, severe sarcoidosis, tuberculosis, severe emphysema, chronic obstructive pulmonary disease (COPD) Gold 3-4, lung fibrosis) Chronic pulmonary hypertension Pregnancy or breastfeeding Persons with any kind of dependency on the investigator or employed by the institution responsible or investigator Persons held in an institution by legal or official order

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| on-pump coronary artery bypass graft surgery<br>Due to the observational design of the study, no study-specific interventions are performed. Except for the above mentioned laboratory analyses, the treatment of the patients is completely guided by the responsible ICU physicians. Study participation does not influence the determination of surgical procedure (on- vs off-pump). | Procedure: on-pump surgery<br>* the surgery will be performed on-pump<br>|
| off-pump coronary artery bypass graft surgery<br>Due to the observational design of the study, no study-specific interventions are performed. Except for the above mentioned laboratory analyses, the treatment of the patients is completely guided by the responsible ICU physicians. Study participation does not influence the determination of surgical procedure (on- vs off-pump). | Procedure: off-pump surgery<br>* the surgery will be performed off-pump<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Differences in plasma concentration of Angiotensinogen |  | between induction of anesthesia and immediately after surgical intervention | 
| Differences in plasma concentration of Renin |  | between induction of anesthesia and immediately after surgical intervention | 
| Differences in plasma concentration of Angiotensin I |  | between induction of anesthesia and immediately after surgical intervention | 
| Differences in plasma concentration of Angiotensin converting enzyme (ACE) |  | between induction of anesthesia and immediately after surgical intervention | 
| Differences in plasma concentration of Angiotensin II |  | between induction of anesthesia and immediately after surgical intervention | 
| Differences in plasma concentration of Aldosterone |  | between induction of anesthesia and immediately after surgical intervention | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Differences in plasma concentration of Angiotensin 1-9 |  | between induction of anesthesia and immediately after surgical intervention | 
| Differences in plasma concentration of Angiotensin 2-7 |  | between induction of anesthesia and immediately after surgical intervention | 
| Differences in plasma concentration of Dipeptidyl-peptidase 3 (DPP3) |  | between induction of anesthesia and immediately after surgical intervention | 
| Incidence of vasoplegia |  | within 12 hours post surgery | 
| Cumulative dose of vasopressors |  | within 12 hours post surgery | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
vasoplegia, vasoplegic shock, cardiopulmonary bypass, cardiac surgery