The Impact of Noradrenaline on Ventriculo-arterial Coupling and Central Cardiovascular Energy Delivery

Study Overview
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Brief Summary
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The study aims to examine how noradrenaline in combination with venous return influences the energy transmission from heart to central circulation and arteries - also called arterio-ventricular coupling.

Detailed Description
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After being informed about the study 40 elective CABG patients with written informed consent will undergo assessment of their arterio-ventricular coupling postoperatively after coronary bypass graft surgery. Whilst still in deep general anesthesia on the CT ICU the study population will be assessed by echocardiographic examination (transthoracic and transesophageal), blood pressure tracing by arterial line, respiratory data and ECG in 4 different situations. Initially the individual patient is either considered fluid responsive (SVV >13%) og non- responsive (SVV<13%) by using stroke volume variation assessed by echocardiography. In case of fluid responsiveness a fluid bolus of 4ml/kg of crystalloid fluid is given until SVV drops below 13% and the patient can be considered as fluid NON responder. Right afterwards the study patient is stabilized with a baseline dose of noradrenaline (NA) intravenously in a supine position (situation 1). Situation 2 will be a slight increase in NA dose stabilizing mean arterial pressure in a baseline + 20mmHg state. After reversing the NA dose back to base line level the patient is allowed a short period of rest to wean of drug effect (4-5 x t1/2, appr. 12min). Subsequently the patient is to be placed in a 20% semi upright position (Anti-Trendelenburg) causing an increase in fluid responsiveness (situation 3). Following a phase of equilibration the dose of NA is again titrated up to obtain a 20mmHg increase in mean arterial pressure (situation 4). There will be logging of arterial pressure curve and VTI-tracing I LVOT simultaneously (ultrapower, uPWR) as well as calculation of energy delivery, cardiac power, oscillatory power and -fraction and both arterial and ventricular elastance in every of those 4 situations.

Official Title
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The Impact of Noradrenaline on Ventriculo-arterial Coupling and Central Cardiovascular Energy Delivery

Conditions
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Heart Diseases

Intervention / Treatment
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* Procedure: Noradrenalin
* Procedure: Noradrenalin
* Procedure: Noradrenalin
* Procedure: Noradrenalin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: elective coronary artery bypass graft surgery requirement for Noradrenaline/Norepinephrine Exclusion Criteria: lack of informed consent patient unsuitable for mean arterial pressure (MAP) elevation of 20mmHg patient requiring different blood pressure range due to medical/surgical needs poor image quality due to patient factors

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 99 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Noradrenalin<br>treatment with 2 different NA concentrations in 2 different states of fluid responsiveness | Procedure: Noradrenalin<br>* Norepinephrine challenge (concentration 'A' ) in fluid responsive position<br>* Other names: Anti-Trendelenburg position/Semiupright position (20degr);Procedure: Noradrenalin<br>* Norepinephrine challenge (concentration 'A') in non-fluid responsive position<br>* Other names: supine position;Procedure: Noradrenalin<br>* Norepinephrine challenge (concentration 'B') in fluid responsive position<br>* Other names: Anti-Trendelenburg position/Semiupright position (20degr);Procedure: Noradrenalin<br>* Norepinephrine challenge (concentration 'B') in non-fluid responsive position<br>* Other names: supine position;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Cardiac Power | Change in Cardiac Power in reaction to both different noradrenaline doses and states of fluid responsiveness. By logging invasive BP curve and tracing left ventricular outflow tract Velocity Time Integral (by echocardiography) simultaneously Total and Mean Cardiac Power (Watt) can be determined. Examining the response to different NA doses relative to fluid responsiveness the effect of NA on arterio-ventricular coupling can be examined. | within 30 minutes after having been stabilised on the cardiothoracic ICU after performed CABG surgery | 
| Change in Oscillatory Power Fraction | Change in Oscillatory Power Fraction (OPF) in reaction to both different noradrenaline doses and states of fluid responsiveness. By logging invasive BP curve and tracing left ventricular outflow tract Velocity Time Integral (by echocardiography) simultaneously Total Cardiac Power (TCP, Watt) and Cardiac Power Output (CPO, Watt) can be determined. By subtracting CPO from TCP, OPF (in %) can be calculated. Examining the response to different NA doses relative to fluid responsiveness the effect of NA on arterio-ventricular coupling can be examined. | within 30 minutes after having been stabilised on the cardiothoracic ICU after performed CABG surgery | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in single beat ventricular elastance | Change in single beat ventricular elastance in reaction to both different noradrenaline doses and states of fluid responsiveness. Ventricular elastance (Ees) can be determined on the bedside by using a single beat measurement of left ventricular ejection fraction, stroke volume, preejection time and ejection time. | within 30 minutes after having been stabilised on the cardiothoracic ICU after performed CABG surgery | 
| Change in single beat arterial elastance | Change in single beat arterial elastance in reaction to both different noradrenaline doses and states of fluid responsiveness. Using an estimative formula Ea can be calculated (Ea=SBPx0.9/SV) and Ea/Ees as a marker of arterio-ventricular coupling can be evaluated. | within 30 minutes after having been stabilised on the cardiothoracic ICU after performed CABG surgery | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Noradrenaline, Heart surgery, Intensive care, Cardiac physiology