Impact of Fluid Resuscitation Therapy on Pulmonary Edema as Measured by Alveolar Fluid Clearance in Patients With Acute Respiratory Distress Syndrome (ARDS) (IROCA)

The need for fluid resuscitation (FR) in ICU patients with acute respiratory distress syndrome (ARDS) is common. Indeed, relative or absolute hypovolemia is a common phenomenon that the intensivist must recognize early and treat promptly. Fluid challenge may have adverse side effects associated with fluid administration. The diffusion within the interstitial space may favor edema formation and cause cardiac dysfunction by volume overload. Edema formation is global and may specifically alter pulmonary alveolar epithelial integrity, leading to enhanced alveolar edema and impaired gas exchange.

Currently, two types of fluids are frequently used, crystalloids and colloids. Among colloids and compared to crystalloids, albumin has the theoretical advantage of causing greater volume expansion.

We hypothesized that a fluid resuscitation therapy with albumin generates less pulmonary edema than a fluid resuscitation therapy with crystalloids.

The aim of our study is to compare alveolar fluid clearance, as a marker of alveolar edema fluid resorption, in 2 groups of patients: those treated with albumin and those treated with crystalloid.

Study Overview

• Status: Unknown
• Conditions: Pulmonary Edema; Hypovolemia; Acute Respiratory Distress Syndrome (ARDS)
• Intervention / Treatment: Drug: 4% albumin

Detailed Description

The main objective of our prospective double blind, randomized, controlled trial is to compare the rate of alveolar fluid clearance, a marker of alveolar edema fluid resorption, in 2 groups of patients with ARDS and suffering from hypovolemia: those treated with albumin and those treated with crystalloid (fluid challenge of 7 mL/kg over 15 minutes, that can be repeated 3 times if hypovolemia persists).

The evolution of respiratory and hemodynamic parameters, as measured by transpulmonary thermodilution (extra-vascular lung water, pulmonary vascular permeability index, cardiac output, global enddiastolic volume), plasma osmolality, plasma oncotic pressure and plasma levels of brain natriuretic peptid (BNP) will be studied one hour and 3 hours after after fluid resuscitation in the two groups. In order to evaluate alveolar epithelial dysfunction in patients receiving either albumin or crystalloid, plasma and alveolar levels of sRAGE (the soluble form of the receptor for advanced glycation endproducts) will be measured by ELISA. Lung aeration and fluid-induced derecruitment will be evaluated with an electrical impedance tomograph (PulmoVista®500, Dräger).

• Study Type: Interventional
• Enrollment (Anticipated): 70
• Phase: Phase 4

Contacts and Locations

Study Locations

• France
  • Clermont-Ferrand, France, 63003
    • Recruiting
    • CHU Clermont-Ferrand

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:

• ICU patients under mechanical ventilation
• Patients within the first 24 hours after onset of moderate or severe ARDS, as defined by the Berlin definition (JAMA. 2012;307(23):2526-2533)
• Hypovolemia requiring fluid resuscitation therapy

Exclusion Criteria:

• Pregnancy
• Age under 18
• Refusal of the protocol
• Contraindications for the use of Voluven© or Ringer Lactate©
• Contraindications for femoral artery catheterization or subclavian venous catheterization

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: albumin; The main objective of our prospective double blind, randomized, controlled trial is to compare the rate of alveolar fluid clearance, a marker of alveolar edema fluid resorption, in 2 groups of patients with ARDS and suffering from hypovolemia: those treated with albumin and those treated with crystalloid (fluid challenge of 7 mL/kg over 15 minutes, that can be repeated 3 times if hypovolemia persists).	Drug: 4% albumin
Other: crystalloid; The main objective of our prospective double blind, randomized, controlled trial is to compare the rate of alveolar fluid clearance, a marker of alveolar edema fluid resorption, in 2 groups of patients with ARDS and suffering from hypovolemia: those treated with albumin and those treated with crystalloid (fluid challenge of 7 mL/kg over 15 minutes, that can be repeated 3 times if hypovolemia persists).	Drug: 4% albumin

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Rate of alveolar fluid clearance	one hour after administration of fluid resuscitation

Secondary Outcome Measures

Outcome Measure	Time Frame
Extra-vascular lung water	one hour and three hours after administration of fluid resuscitation
Pulmonary vascular permeability index	one hour and three hours after administration of fluid resuscitation
Global enddiastolic volume index	one hour and three hours after administration of fluid resuscitation
mean arterial pressure	one hour and three hours after administration of fluid resuscitation
cardiac output	one hour and three hours after administration of fluid resuscitation
pulse pressure variation	one hour and three hours after administration of fluid resuscitation
stroke volume variation	one hour and three hours after administration of fluid resuscitation
central venous venous oxygenation	one hour and three hours after administration of fluid resuscitation
central venous pressure	one hour and three hours after administration of fluid resuscitation
PaO2	one hour and three hours after administration of fluid resuscitation
lung compliance	one hour and three hours after administration of fluid resuscitation
airways resistance	one hour and three hours after administration of fluid resuscitation
lung injury score	one hour and three hours after administration of fluid resuscitation
Plasma levels of sRAGE	one hour and three hours after administration of fluid resuscitation
Alveolar levels of sRAGE	one hour and three hours after administration of fluid resuscitation
Brain natriuretic peptide levels	one hour and three hours after administration of fluid resuscitation
Plasma osmolarity	one hour and three hours after administration of fluid resuscitation
Oncotic pressure	one hour and three hours after administration of fluid resuscitation
Electrical impedance tomography	one hour and three hours after administration of fluid resuscitation
Mortality	Day 20, Day 90

Collaborators and Investigators

• Sponsor: University Hospital, Clermont-Ferrand
• Collaborators: Université d'Auvergne; R2D2 Retinoids, Reproduction Developmental Diseases
• Investigators: Principal Investigator: Matthieu JABAUDON, University Hospital, Clermont-Ferrand

Study record dates

Study Major Dates

• Study Start: December 1, 2012
• Primary Completion (Anticipated): April 1, 2017
• Study Completion (Anticipated): May 1, 2017

Study Registration Dates

• First Submitted: December 10, 2012
• First Submitted That Met QC Criteria: January 7, 2013
• First Posted (Estimate): January 9, 2013

Study Record Updates

• Last Update Posted (Estimate): July 29, 2016
• Last Update Submitted That Met QC Criteria: July 28, 2016
• Last Verified: July 1, 2016

More Information

Terms related to this study

• Keywords: Intensive care unit; Crystalloid; Acute respiratory distress syndrome (ARDS); Hypovolemia; Pulmonary edema; Hydroxyethyl Starch; Alveolar fluid clearance; Alveolar epithelial dysfunction; Receptor for advanced glycation end-products (RAGE); Fluid resuscitation therapy
• Additional Relevant MeSH Terms: Pathologic Processes; Respiratory Tract Diseases; Respiration Disorders; Lung Diseases; Disease; Infant, Newborn, Diseases; Lung Injury; Infant, Premature, Diseases; Syndrome; Edema; Respiratory Distress Syndrome; Respiratory Distress Syndrome, Newborn; Acute Lung Injury; Pulmonary Edema; Hypovolemia
• Other Study ID Numbers: CHU-0134