Early Haemodynamic Optimization Using Preload Dependence During Septic Shock = EHOSS-1 (EHOSS-1)

Effect of Haemodynamic Optimization Using Preload Dependence Indexes and Pulmonary Thermodilution on Cardiovascular Failure Duration During Septic Shock: a Randomized Study

Haemodynamic optimization is of paramount importance in septic shock, but is really consensual and standardized during the first 6 hours of treatment. Haemodynamic treatment including fluid loading management, vasoactive treatment and oxygen transport optimization is mainly based on expert recommendations or non-randomized trials. Recently, preload dependence indexes such as pulse pressure variation have been shown to be more accurate to predict fluid responsiveness than static indexes such as filling pressures. However, whether using preload dependence indexes changes septic shock prognostic remains to date unknown. The aim of this non-blinded randomized controlled trial is to assess whether haemodynamic optimization using preload dependence indexes and pulmonary thermodilution 1. reduces septic shock duration assessed by administration duration of vasoactive treatment (primary end point), 2. reduces regional hypoperfusion assessed by arterial lactate, 3. reduces lung hydrostatic oedema linked to excessive fluid loading (assessed by PaO2/FIO2 ratio and extravascular lung water). 4. reduces organ dysfunction (assessed by the SOFA score), ICU stay and 7 and 28 day mortality Control group is managed with an algorithm using filling pressures to drive haemodynamic treatment.

Study Overview

• Status: Completed
• Conditions: Septic Shock
• Intervention / Treatment: Drug: FLUID MANAGEMENT GUIDED WITH PRELOAD-DEPENDENCE PARAMETERS (VOLUVEN ®); Drug: STANDARD-GUIDED FLUID MANAGEMENT (VOLUVEN ®)

• Study Type: Interventional
• Enrollment (Actual): 61
• Phase: Not Applicable

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:

• age over 18 years
• and fulfilment of two of four criteria for the systemic inflammatory response syndrome
• and systolic blood pressure no higher than 90 mm Hg (after a crystalloid-fluid challenge of 25 ml per kilogram of body weight over a 30-minute period)
• and documented or suspected infection

Exclusion Criteria:

• delay between first observation of hypotension and inclusion above 12 hours
• pregnancy
• acute coronary syndrome
• acute cerebral vascular event (< 1 month),
• contraindication to central venous catheterization in the superior vena cava territory
• contraindication to femoral arterial catheterization
• active haemorrhage
• burn injury
• trauma
• requirement for immediate surgery (< 6 hours)
• acute pulmonary oedema of cardiogenic origin
• do-not-resuscitate status, or advanced directives restricting implementation of the protocol.
• Informed consent not obtained from the patient or surrogates
• Patient already included in another therapeutic trial
• patient previously included in the same therapeutic trial

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: PRELOAD DEPENDENCE; in this arm, fluid loading is administered with an algorithm using preload dependence indexes (variation in cardiac output in response to passive leg raising).	Drug: FLUID MANAGEMENT GUIDED WITH PRELOAD-DEPENDENCE PARAMETERS (VOLUVEN ®); in this arm, fluid loading is administered with an algorithm using preload dependence indexes. This algorithm is used every hour during the first 6 hours after inclusion, then every 4 hours until vasopressor weaning, and whenever mean arterial pressure fell below 65 mm Hg. Fluid loading is performed with cristalloids or colloids at the discretion of the attending physician.; Other Names: Drug : ringer lactate, 0.9% saline, VOLUVEN ®; Procedure: haemodynamic algorithm (see below)
Active Comparator: CONTROL	Drug: STANDARD-GUIDED FLUID MANAGEMENT (VOLUVEN ®); in this arm, fluid loading is administered with an algorithm using central venous pressure. This algorithm is used every hour during the first 6 hours after inclusion, then every 4 hours until vasopressor weaning, and whenever mean arterial pressure fell below 65 mm Hg. Fluid loading is performed with cristalloids or colloids at the discretion of the attending physician.; Other Names: Drug : ringer lactate, 0.9% saline, VOLUVEN ®; Procedure: haemodynamic algorithm (see below)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to septic shock resolution	shock resolution is defined by vasopressor weaning	28 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
mortality		28 days
Ventilator free days		28 days
number of days with hyperlactactatemia		28 days
number of days with pulmonary edema	assessed by transpulmonary thermodilution	28 jours

Collaborators and Investigators

• Sponsor: Hospices Civils de Lyon

Publications and helpful links

General Publications

• Richard JC, Bayle F, Bourdin G, Leray V, Debord S, Delannoy B, Stoian AC, Wallet F, Yonis H, Guerin C. Preload dependence indices to titrate volume expansion during septic shock: a randomized controlled trial. Crit Care. 2015 Jan 8;19(1):5. doi: 10.1186/s13054-014-0734-3.

Study record dates

Study Major Dates

• Study Start: July 1, 2007
• Primary Completion (Actual): August 1, 2013

Study Registration Dates

• First Submitted: October 11, 2013
• First Submitted That Met QC Criteria: October 30, 2013
• First Posted (Estimate): October 31, 2013

Study Record Updates

• Last Update Posted (Estimate): October 31, 2013
• Last Update Submitted That Met QC Criteria: October 30, 2013
• Last Verified: October 1, 2013

More Information

Terms related to this study

• Keywords: Randomized controlled trial; Septic shock; Preload dependence; Pulmonary thermodilution
• Additional Relevant MeSH Terms: Pathologic Processes; Infections; Systemic Inflammatory Response Syndrome; Inflammation; Sepsis; Shock, Septic; Shock; Plasma Substitutes; Blood Substitutes; Hydroxyethyl Starch Derivatives
• Other Study ID Numbers: 2006.440