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

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.

Study Overview

• Status: Completed
• Conditions: Heart Diseases
• Intervention / Treatment: Procedure: Noradrenalin; Procedure: Noradrenalin; Procedure: Noradrenalin; Procedure: Noradrenalin

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 49
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Norway
  • Trondheim, Norway, 7006
    • St Olavs Hospital, Dep. for Anesthesia & Intensive care. Section of cardiothoracic Anesthesia and -intensive Care.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 99 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Noradrenalin; treatment with 2 different NA concentrations in 2 different states of fluid responsiveness

Procedure: Noradrenalin; Norepinephrine challenge (concentration 'A' ) in fluid responsive position; Other Names: Anti-Trendelenburg position/Semiupright position (20degr); Procedure: Noradrenalin; Norepinephrine challenge (concentration 'A') in non-fluid responsive position; Other Names: supine position; Procedure: Noradrenalin; Norepinephrine challenge (concentration 'B') in fluid responsive position; Other Names: Anti-Trendelenburg position/Semiupright position (20degr); Procedure: Noradrenalin; Norepinephrine challenge (concentration 'B') in non-fluid responsive position; Other Names: supine position

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: St. Olavs Hospital
• Investigators: Study Director: Hilde Pleym (Head of Department), md, PhD, St. Olavs Hospital

Study record dates

Study Major Dates

• Study Start (Actual): March 1, 2021
• Primary Completion (Actual): December 31, 2021
• Study Completion (Actual): December 31, 2021

Study Registration Dates

• First Submitted: February 8, 2021
• First Submitted That Met QC Criteria: February 8, 2021
• First Posted (Actual): February 9, 2021

Study Record Updates

• Last Update Posted (Actual): January 5, 2022
• Last Update Submitted That Met QC Criteria: January 4, 2022
• Last Verified: January 1, 2022

More Information

Terms related to this study

• Keywords: Intensive care; Heart surgery; Noradrenaline; Cardiac physiology
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Heart Diseases; Physiological Effects of Drugs; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Autonomic Agents; Peripheral Nervous System Agents; Adrenergic alpha-Agonists; Adrenergic Agonists; Sympathomimetics; Vasoconstrictor Agents; Norepinephrine
• Other Study ID Numbers: 2019/287

Drug and device information, study documents

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