Esmolol Effects on Heart and Inflammation in Septic Shock (ESMOSEPSIS)

Anti-inflammatory and Cardiac Effects of Esmolol in Septic Shock. ESMOSEPSIS Study

Beta adrenergic system, over-activated in septic shock patients, is a key modulator of the inflammatory response. Experimental works demonstrated that Esmolol, an highly selective beta-1 blocker, reduces heart rate and regulates the inflammatory response. A recent mono centric, double blind, randomized clinical work in septic shock patients has shown that Esmolol administration is safe and reduces effectively heart rate. However there are only sparse data on 1) regional and micro-circulation, 2) inflammation modulation in human resuscitated septic shock patients treated by esmolol.

Study Overview

• Status: Unknown
• Conditions: Septic Shock
• Intervention / Treatment: Drug: Esmolol

• Study Type: Interventional
• Enrollment (Anticipated): 25
• Phase: Phase 2

Contacts and Locations

Study Locations

• France
  • Nancy, France, 54511
    • Recruiting
    • Chu de Nancy
    • Contact: Bruno Levy, MD PhD; Phone Number: 0033383154469; Email: b.levy@chu-nancy.fr

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• septic shock patients following the definition of the Surviving Sepsis Campaign
• femoral and central venous catheters for thermodilution monitoring
• fluid optimization
• with a cardiac index > 3 l/min/m2
• Heart Rate >100 /min

Exclusion Criteria:

• Cardiogenic shock
• Bradycardia
• History of Severe Asthma
• Indications against esmolol

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• 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: ESMOLOL; Resuscitated, hyperkinetic septic shock patients are treated with esmolol in order to reduce heart rate of 20% during 6 hours. During the intervention period, multimodal macro and micro hemodynamic data are recorded.	Drug: Esmolol; After, at least six hours of hemodynamic optimization, patients with an hyper dynamic shock received a conventional management with a continuous infusion of Esmolol titrated to gain a 20% reduction in heart rate. This infusion is maintained for six hours.; Other Names: Brevibloc

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Hemodynamic effects of Esmolol in septic shock patients (Value of cardiac index l/min/m2)	Compare, in septic shock patients, the mean cardiac index before and after administration of Esmolol.	Before administration (H0) and each hour (H1-H2-H3-H4-H5-H6) during the whole administration period and one hour after Esmolol cessation (H7)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Effects on vasopressor requirement (amount of norepinephrine infused in microgram/kg) during Esmolol administration		Record of each change in vasopressor dosage to maintain a mean arterial pressure at 70 mmHg during the whole Esmolol administration period (H0 to H6) and one hour after esmolol cessation (H7)
Microcirculatory and regional circulation effects of Esmolol in septic shock patient	NIRS (near-infrared spectroscopy) SDF (Sidestream Dark Field imaging) / Limon (non-invasive measurement of liver function and splanchnic perfusion monitoring) are used to asses microcirculatory and regional circulation effects	Before (H0), 6 hours after Esmolol introduction (H6) and 1 hour after esmolol cessation (H7)
Changes in the Cytokine pattern(pro and anti inflammatory cytokines assay) induced by Esmolol administration in septic shock patients		Before administration of Esmolol (H0) and 6 hours after introduction of Esmolol (H6)
Description of the cardiac function during Esmolol Administration in septic shock patients	Use of Echocardiography to assess ventricular function	Before administration (H0), at 4 hours, 6 hours after introduction and 1 hours after esmolol cessation

Collaborators and Investigators

• Sponsor: Central Hospital, Nancy, France
• Collaborators: Baxter Healthcare Corporation
• Investigators: Principal Investigator: Bruno Levy, MD PhD, Chu de Nancy; Principal Investigator: Antoine Kimmoun, MD, Chu de Nancy

Publications and helpful links

General Publications

• Levy B, Fritz C, Piona C, Duarte K, Morelli A, Guerci P, Kimmoun A, Girerd N. Hemodynamic and anti-inflammatory effects of early esmolol use in hyperkinetic septic shock: a pilot study. Crit Care. 2021 Jan 7;25(1):21. doi: 10.1186/s13054-020-03445-w.

Study record dates

Study Major Dates

• Study Start: December 1, 2013
• Primary Completion (Anticipated): December 1, 2016
• Study Completion (Anticipated): June 1, 2017

Study Registration Dates

• First Submitted: January 29, 2014
• First Submitted That Met QC Criteria: February 19, 2014
• First Posted (Estimate): February 21, 2014

Study Record Updates

• Last Update Posted (Estimate): January 28, 2016
• Last Update Submitted That Met QC Criteria: January 27, 2016
• Last Verified: January 1, 2016

More Information

Terms related to this study

• Keywords: Hemodynamic; Septic Shock; Esmolol; Inflammatory status; Beta adrenergic modulation
• Additional Relevant MeSH Terms: Pathologic Processes; Infections; Systemic Inflammatory Response Syndrome; Inflammation; Sepsis; Shock, Septic; Shock; Physiological Effects of Drugs; Adrenergic beta-Antagonists; Adrenergic Antagonists; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Adrenergic beta-1 Receptor Antagonists; Esmolol
• Other Study ID Numbers: 2012-004532-32