Enhanced Lung Protective Ventilation for ARDS Patients With PrismaLung

Study Overview
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Brief Summary
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Acute Respiratory Distress Syndrome (ARDS) still remains associated with a mortality rate of 30 - 45 % despite improvement in mechanical ventilation. Driving pressure, defined as the difference between the end-inspiratory and the end-expiratory airway pressure, appears as an important factor contributing to mortality in patients with the ARDS. In patients already receiving a conventional tidal volume of 6 ml/kg predicted body weight (PBW), a driving pressure ≥ 14 cmH2O increases the risk of death in the hospital. One mean to lower the driving pressure is to decrease the tidal volume such that from 6 to 4 ml/kg predicted body weight. However, this strategy promotes hypercarbia by reducing the alveolar ventilation, providing the respiratory rate is constant. In this setting, implementing an extracorporeal CO2 removal (ECCO2R) therapy may offset the associated hypercarbia. The investigators have previously demonstrated that combining a membrane oxygenator within an hemofiltration circuit provides efficacious low flow ECCO2R on a renal replacement therapy monitor. In this study, we thought to investigate the efficacy of the PrismaLung stand-alone therapy. Using a PrismaFlex monitor and a HP-X circuit, a neonatal membrane oxygenator (PrismaLung) is used to provide decarboxylation without renal replacement therapy. The study will consist in three periods: The first period will address the efficacy of the PrismaLung device at tidal volume of 6 and 4 ml/kg PBW using an off-on-off design. The second part of the study will investigate the effect of varying the sweep gas flow and the mixture of the sweep gas on the CO2 removal rate (random order). The third part will compare three ventilatory strategies applied in a cross-over design : Minimal distension: Tidal volume 4 ml/kg PBW and positive end-expiratory pressure (PEEP) based on the ARDSNet PEEP/FiO2 table (ARMA). Maximal recruitment: 4 ml/kg PBW and PEEP adjusted to maintain a plateau pressure between 23 - 25 cmH2O. Standard: Tidal volume 6 ml/kg and PEEP based on the ARDSNet PEEP/FiO2 table (ARMA). Each strategies will be apply in a random order for a duration of 22 hours. Pulmonary inflammatory and fibrosis pathway will be assess before and after each period using bronchoalveolar lavage (BAL) samples. Systemic inflammatory cytokines will also be investigate. Main measurements will include respiratory mechanics, transpulmonary pressure, work of breathing, end-expiratory lung volume and tidal ventilation using electrical impedance tomography.

Official Title
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Enhanced Lung Protective Ventilation for ARDS Patients With PrismaLung

Conditions
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Acute Respiratory Distress Syndrome

Intervention / Treatment
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* Device: PrismaLung


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: ARDS moderate or severe (Berlin criteria) Onset < 48 h Driving pressure ≥ 14 cmH2O Exclusion Criteria: Lack of consent or social protection Chronic respiratory failure (requiring Oxygen or NIPPV) Severe hypoxemia: PaO2/FIO2 < 100 with PEEP ≥ 18 cmH2O AND FIO2 = 1 Acute Renal Failure requiring RRT DNR order or death expected within the next 72 hours Planned surgery or out-of-ICU transportation expected within the next 72 hours Heparin allergy Contraindication to jugular vein catheterization Intracranial Hypertension

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: Supportive Care
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Minimal Distension<br>Tidal volume 4 ml/kg PBW and PEEP based on the ARDSNet PEEP/FiO2 table (ARMA) + ECCO2R | Device: PrismaLung<br>* Low flow Extracorporeal CO2 removal using a 0.32 m² membrane oxygenator<br>|
| Experimental: Maximal Recruitment<br>Tidal volume 4 ml/kg PBW and PEEP adjusted to maintain plateau pressure between 23 - 25 cmH2O + ECCO2R | Device: PrismaLung<br>* Low flow Extracorporeal CO2 removal using a 0.32 m² membrane oxygenator<br>|
| Active Comparator: Standard<br>Tidal volume 6 ml/kg PBW and PEEP based on the ARDSNet PEEP/FiO2 table (ARMA) without ECCO2R | Device: PrismaLung<br>* Low flow Extracorporeal CO2 removal using a 0.32 m² membrane oxygenator<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in PaCO2 | 20 % decrease in PaCO2 after initiation of ECCO2R (PrismaLung) at tidal volume of 4 ml/kg PBW versus 4 ml/kg PBW without ECCO2R. | 15 min after initiation of ECCO2R (PrismaLung) at tidal volume of 4 ml/kg PBW (during the first part of the study). | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| PaCO2 | Arterial blood gas | q15 min during part 1 and part 2 of the study. In the third part, measurement at baseline, 1 hour and 22 hours in each arm. | 
| CO2 removal rate | Using both the blood side and the gas side equation | q15 min during part 1 and part 2 of the study. In the third part, measurement at baseline, 1 hour and 22 hours in each arm. | 
| Respiratory mechanics work of breathing | Using oesophageal ballon (NutriVent catheter) and FluxMed monitor (MBMed) | q15 min during part 1 and part 2 of the study. In the third part, measurement at baseline, 1 hour and 22 hours in each arm. | 
| Transpulmonary pressure | Using oesophageal ballon (NutriVent catheter) and FluxMed monitor (MBMed) | q15 min during part 1 and part 2 of the study. In the third part, measurement at baseline, 1 hour and 22 hours in each arm. | 
| Work of breathing | Using oesophageal ballon (NutriVent catheter) and FluxMed monitor (MBMed) | q15 min during part 1 and part 2 of the study. In the third part, measurement at baseline, 1 hour and 22 hours in each arm. | 
| EIT | Electrical Impedance Tomography using BB² (Swisstom) | q15 min during part 1 and part 2 of the study. In the third part, measurement at baseline, 1 hour and 22 hours in each arm. | 
| EELV | End expiratory Lung volume using nitrogen wash-in wash-out method (Engstrom GE) | q15 min during part 1 and part 2 of the study. In the third part, measurement at baseline, 1 hour and 22 hours in each arm. | 
| Plasma Cytokines | Elisa using plasma samples | Only in the third part, measurement at baseline, 1 hour and 22 hours in each arm. | 
| Pulmonary Cytokines | Elisa using BAL samples | Only in the third part, measurement at baseline, 1 hour and 22 hours in each arm. | 
| Pulmonary Type III Procollagen | RIA using plasma and BAL samples | Only in the third part, measurement at baseline, 1 hour and 22 hours in each arm. | 
| Pulmonary Inflammatory and Fibrotic pathway | mRNA | Only in the third part, measurement at baseline, 1 hour and 22 hours in each arm. |