Clinical trial NCT01763853: Impact of Fluid Resuscitation Therapy on Pulmonary Edema as Measured by Alveolar Fluid Clearance in Patients With Acute Respiratory Distress Syndrome (ARDS)
Official title: Impact of Fluid Resuscitation Therapy on Pulmonary Edema as Measured by Alveolar Fluid Clearance in Patients With Acute Respiratory Distress Syndrome (ARDS)
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE4
Conditions: Acute Respiratory Distress Syndrome (ARDS)
Hypovolemia
Pulmonary Edema
Keywords: Acute respiratory distress syndrome (ARDS)
Pulmonary edema
Alveolar fluid clearance
Alveolar epithelial dysfunction
Receptor for advanced glycation end-products (RAGE)
Fluid resuscitation therapy
Hypovolemia
Crystalloid
Hydroxyethyl Starch
Intensive care unit
Lead sponsor: University Hospital, Clermont-Ferrand
Sponsor class: OTHER
Collaborators: name: R2D2 Retinoids, Reproduction Developmental Diseases
name: Université d'Auvergne
First posted: 2013-01-09
Enrollment: 70
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

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).

Eligibility criteria: 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

Primary outcomes:
measure: Rate of alveolar fluid clearance
timeFrame: one hour after administration of fluid resuscitation
Secondary outcomes:
measure: Extra-vascular lung water
timeFrame: one hour and three hours after administration of fluid resuscitation
measure: Pulmonary vascular permeability index
timeFrame: one hour and three hours after administration of fluid resuscitation
measure: Global enddiastolic volume index
timeFrame: one hour and three hours after administration of fluid resuscitation
measure: mean arterial pressure
timeFrame: one hour and three hours after administration of fluid resuscitation
measure: cardiac output
timeFrame: one hour and three hours after administration of fluid resuscitation
measure: pulse pressure variation
timeFrame: one hour and three hours after administration of fluid resuscitation
measure: stroke volume variation
timeFrame: one hour and three hours after administration of fluid resuscitation
measure: central venous venous oxygenation
timeFrame: one hour and three hours after administration of fluid resuscitation
measure: central venous pressure
timeFrame: one hour and three hours after administration of fluid resuscitation
measure: PaO2
timeFrame: one hour and three hours after administration of fluid resuscitation
measure: lung compliance
timeFrame: one hour and three hours after administration of fluid resuscitation
measure: airways resistance
timeFrame: one hour and three hours after administration of fluid resuscitation
measure: lung injury score
timeFrame: one hour and three hours after administration of fluid resuscitation
measure: Plasma levels of sRAGE
timeFrame: one hour and three hours after administration of fluid resuscitation
measure: Alveolar levels of sRAGE
timeFrame: one hour and three hours after administration of fluid resuscitation
measure: Brain natriuretic peptide levels
timeFrame: one hour and three hours after administration of fluid resuscitation
measure: Plasma osmolarity
timeFrame: one hour and three hours after administration of fluid resuscitation
measure: Oncotic pressure
timeFrame: one hour and three hours after administration of fluid resuscitation
measure: Electrical impedance tomography
timeFrame: one hour and three hours after administration of fluid resuscitation
measure: Mortality
timeFrame: Day 20, Day 90
Other outcomes:
Locations:
city: Clermont-Ferrand
country: France
facility: CHU Clermont-Ferrand
Study officials:
affiliation: University Hospital, Clermont-Ferrand
name: Matthieu JABAUDON
role: PRINCIPAL_INVESTIGATOR
References: