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

Study Overview
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Brief Summary
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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
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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).

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

Conditions
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Acute Respiratory Distress Syndrome (ARDS), Hypovolemia, Pulmonary Edema

Intervention / Treatment
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* Drug: 4% albumin


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: albumin<br>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<br> <br> |
| Other: crystalloid<br>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<br> <br> |

What is the study measuring?
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Primary Outcome Measures

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

Secondary Outcome Measures

| Outcome Measure | Measure Description | 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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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