Cardiovascular Effects of Norepinephrine

Cardiac Effects of Norepinephrine After the Initial Phase of Septic Shock

Previous studies of our team reported the improvement of myocardial contractility both on hemodynamic parameters (by transpulmonary thermodilution) and morphological (by transthoracic echocardiography: TTE), during the early phase of septic shock (during the first 4 hours management of septic shock).

However, one can wonder about the effect of NAD on myocardial cardiac ouput and contractility beyond the early phase of septic shock, more precisely beyond the first 24 hours. Indeed, while it continues to act on the "stressed" blood volume and the diastolic left ventricular perfusion by increasing the diastolic arterial pressure (DAP), it has been reported in old studies that beyond the early phase, the sensitivity of the β1-adrenergic receptors is altered due to the phenomenon of internalization of these receptors, leading to a reduction of the myocardial response to catecholamines.

The investigators can then wonder whether norepinephrine still exerts a positive effect on myocardial contractility via the increase in DAP, despite an alteration of the β1-adrenergic pathway.

To answer this question, the investigators proposed to evaluate the effects of norepinephrine by TTE on cardiac contractility after the initial phase.

Study Overview

• Status: Recruiting
• Conditions: Septic Shock
• Intervention / Treatment: Other: transthoracic echocardiography

Detailed Description

Patients presenting with septic shock for 24 hours or more and meeting the inclusion criteria may be included.

The course of the study will be as follows:

T0: collection (as part of usual care) of clinical circulatory parameters (heart rate, systolic/diastolic/mean blood pressure) and biological parameters (arterial lactate and ScVo2) and performance of echocardiography.

Parameters collected during TTE:

• Concerning the main judgment criterion and the secondary judgment criteria:

  • Left ventricular ejection fraction (LVEF) by the Simpson Biplane method,
  • Cardiac output and cardiac index by continuity equation (measurement of left ventricular outflow chamber (mm) and sub-aortic time-velocity integral (cm/s)).
  • Tricuspid Annular Systolic Excursion (TAPSE) (mm)
  • S wave at the tricuspid ring (cm/s)

• Other parameters collected systematically:

  • Surface of the left ventricle (end-systolic and end-diastolic),
  • Global strain of the left ventricle
  • Mitral Annular Plane Systolic Excursion (MAPSE) (mm)
  • Left ventricular filling pressure (LVRP) (at the mitral annulus, E, A, e', S' waves, E/A ratio, E/e');
  • Maximum tricuspid regurgitation velocity (m/s) to estimate systolic pulmonary arterial pressure (PAPs) (mmHg)

T1: After the clinician in charge introduces or increases norepinephrine to achieve MAP ≥ 65mmHg, T1 will be when the goal of MAP ≥ 65mmHg is reached. This will be the target MAP for the management of septic shock of the patient in question according to the recommendations of learned societies.

Collection of clinical and biological circulatory parameters and performance of the TTE. The parameters collected will be the same as at T0.

• Study Type: Observational
• Enrollment (Estimated): 49

Contacts and Locations

• Study Contact: Name: Olfa Hamzaoui; Phone Number: 0033 3 10 73 69 73; Email: ohamzaoui@chu-reims.fr

Study Locations

• France
  • Reims, France, 51092
    • Recruiting
    • Chu Reims
    • Contact: Damien JOLLY; Phone Number: 33 326788472; Email: djolly@chu-reims.fr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Adult patients suffering from septic shock, after 24 hours of their diagnosis. Presenting with Mean arterial pressure (MAP)<65 mmHg or the target MAP For whom the physician in charge decided to increase the norepinephrine dose

Description

Inclusion Criteria:

• Adult patients >18 years old
• Septic shock after 24 hours from its diagnosis
• MAP<65 mmHg for which the physician in charge decided to increase NE

Exclusion Criteria:

• Patient under Dobutamine
• Pregnancy
• Do not resuscitation decision

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort

Intervention / Treatment

Patients with septic shock for 24 hours or more; Adult patients suffering from septic shock, after 24 hours of their diagnosis. Presenting with Mean arterial pressure (MAP)<65 mmHg or the target MAP For whom the physician in charge decided to increase the norepinephrine dose

Other: transthoracic echocardiography; Concerning the main judgment criterion and the secondary judgment criteria:Left ventricular ejection fraction (LVEF) by the Simpson Biplane method,Cardiac output and cardiac index by continuity equation (measurement of left ventricular outflow chamber (mm) and sub-aortic time-velocity integral (cm/s)).Tricuspid Annular Systolic Excursion (TAPSE) (mm)S wave at the tricuspid ring (cm/s); Other parameters collected systematically:Surface of the left ventricle (end-systolic and end-diastolic),Global strain of the left ventricleMitral Annular Plane Systolic Excursion (MAPSE) (mm)Left ventricular filling pressure (LVRP) (at the mitral annulus, E, A, e', S' waves, E/A ratio, E/e');Maximum tricuspid regurgitation velocity (m/s) to estimate systolic pulmonary arterial pressure (PAPs) (mmHg)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
The effect of the increase of Norepinephrine dose after restoring MAP on cardiac contractility evaluated by TTE : the left ventricular ejection fraction	through study completion, an average of 30 minutes

Collaborators and Investigators

• Sponsor: CHU de Reims

Study record dates

Study Major Dates

• Study Start (Actual): April 21, 2023
• Primary Completion (Estimated): March 21, 2025
• Study Completion (Estimated): December 21, 2025

Study Registration Dates

• First Submitted: February 7, 2023
• First Submitted That Met QC Criteria: February 27, 2023
• First Posted (Actual): March 9, 2023

Study Record Updates

• Last Update Posted (Actual): August 22, 2024
• Last Update Submitted That Met QC Criteria: August 21, 2024
• Last Verified: August 1, 2024

More Information

Terms related to this study

• Keywords: ECHOCARDIOGRAPHY; CARDIAC FUNCTION; NOREPINEPHRINE; SEPTIC SHOCK
• Additional Relevant MeSH Terms: Pathologic Processes; Infections; Systemic Inflammatory Response Syndrome; Inflammation; Sepsis; Shock, Septic; Shock
• Other Study ID Numbers: PZ23020*

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

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