PROVE: Enhanced Lung Protective Ventilation With ECCO2R During ARDS
Study Details
Study Description
Brief Summary
Acute Respiratory Distress Syndrome (ARDS) is associated with a mortality rate of 30 - 45 % and required invasive mechanical ventilation (MV) in almost 85 % of patients[1]. During controlled MV, driving pressure (i.e., the difference between end-inspiratory and end-expiratory airway pressure) depends of both tidal volume and respiratory system compliance. Either excessive tidal volume or reduced lung aeration may increase the driving pressure. ARDS patients receiving tidal volume of 6 ml/kg predicted body weight (PBW) and having a day-1 driving pressure ≥ 14 cmH2O have an increased risk of death in the hospital[2]. Seemly, in the LUNG SAFE observational cohort, ARDS patients having a day-1 driving pressure < 11 cmH2O had the lowest risk of death in the hospital[1]. Hence, driving pressure acts as a major contributor of mortality in ARDS, and probably reflects excessive regional lung distension resulting in pro-inflammatory and fibrotic biological processes. Whether decreasing the driving pressure by an intervention change mortality remains an hypothesis; but one of means is to decrease the tidal volume from 6 to 4 ml/ kg predicted body weight (PBW). However, this strategy promotes hypercarbia, at constant respiratory rate, by decreasing the alveolar ventilation. In this setting, implementing an extracorporeal CO2 removal (ECCO2R) therapy prevents from hypercarbia. A number of low-flow ECCO2R devices are now available and some of those use renal replacement therapy (RRT) platform. The investigators previously reported that combining a membrane oxygenator (0.65 m²) within a hemofiltration circuit provides efficacious low flow ECCO2R and blood purification in patients presenting with both ARDS and Acute Kidney injury[3].
This study aims to investigate the efficacy of an original ECCO2R system combining a 0.67 m² membrane oxygenator (Lilliput 2, SORIN) inserted within a specific circuit (HP-X, BAXTER) and mounted on a RRT monitor (PrismafleX, BAXTER). Such a therapy only aims to provide decarboxylation but not blood purification and has the huge advantage to be potentially implemented in most ICUs without requiring a specific ECCO2R device. The study will consist in three periods:
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The first period will address the efficacy of this original ECCO2R system at tidal volume of 6 and 4 ml/kg PBW using an off-on-off design.
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The second part will investigate the effect of varying the sweep gas flow (0-2-4-6-8-10 l/min) and the mixture of the sweep gas (Air/O2) on the CO2 removal rate.
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The third part will compare three ventilatory strategies applied in a crossover design:
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Minimal distension: Tidal volume 4 ml/kg PBW and positive end-expiratory pressure (PEEP) based on the ARDSNet PEEP/FiO2 table (ARMA).
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Maximal recruitment: 4 ml/kg PBW and PEEP adjusted to maintain a plateau pressure between 23 - 25 cmH2O.
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Standard: Tidal volume 6 ml/kg and PEEP based on the ARDSNet PEEP/FiO2 table (ARMA).
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
N/A |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Minimal distension Tidal volume 4 ml/kg PBW and positive end-expiratory pressure (PEEP) based on the ARDSNet PEEP/FiO2 table (ARMA) + ECCO2R (sweep gas = 8 L/min, blood flow = 400 mL/min) |
Device: Low flow Extracorporeal CO2 removal
Low flow Extracorporeal CO2 removal using a 0.67 m² membrane oxygenator (Lilliput 2) and a specific circuit (HP-X) mounted on a RRT monitor (PrismafleX)
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| Experimental: Maximal recruitment Tidal volume 4 ml/kg PBW and PEEP adjusted to maintain a plateau pressure between 23 - 25 cmH2O + ECCO2R (sweep gas = 8 L/min, blood flow = 400 mL/min) |
Device: Low flow Extracorporeal CO2 removal
Low flow Extracorporeal CO2 removal using a 0.67 m² membrane oxygenator (Lilliput 2) and a specific circuit (HP-X) mounted on a RRT monitor (PrismafleX)
|
| Active Comparator: Standard Tidal volume 6 ml/kg PBW and positive end-expiratory pressure (PEEP) based on the ARDSNet PEEP/FiO2 table (ARMA) without ECCO2R (no sweep gas flow, blood flow = 400 mL/min) |
Device: Low flow Extracorporeal CO2 removal
Low flow Extracorporeal CO2 removal using a 0.67 m² membrane oxygenator (Lilliput 2) and a specific circuit (HP-X) mounted on a RRT monitor (PrismafleX)
|
Outcome Measures
Primary Outcome Measures
- Change in PaCO2 [15 minutes after initiation of ECCO2R at tidal volume of 4 ml/kg PBW.]
20 % decrease in PaCO2 after initiation of ECCO2R at tidal volume of 4 ml/kg PBW (as compared to 4 ml/kg without ECCO2R)
Secondary Outcome Measures
- PaCO2 [each 15 minutes up to the third hour (Part I and II of the study). In the third part, measurement at baseline and at 1 hour and at 22 hours into each arm.]
Arterial blood gas analyser (RAPIDPoint 500)
- CO2 removal rate [each 15 minutes up to the third hour (Part I and II of the study). In the third part, measurement at baseline and at 1 hour and at 22 hours into each arm.]
Using measurements from both the blood side and the gas side (two methods)
- Transpulmonary pressure and work of breathing [each 15 minutes up to the third hour (Part I and II of the study). In the third part, measurement at baseline and at 1 hour and at 22 hours into each arm.]
Using an oesophageal balloon catheter (NutriVent catheter) and a dedicated monitor (FluxMed, MBMed)
- Regional tidal ventilation [each 15 minutes up to the third hour (Part I and II of the study). In the third part, measurement at baseline and at 1 hour and at 22 hours into each arm.]
Using an Electrical Impedance Tomography device (BB², Swisstom)
- End-expiratory Lung Volume [each 15 minutes up to the third hour (Part I and II of the study). In the third part, measurement at baseline and at 1 hour and at 22 hours into each arm.]
Using the nitrogen wash-in wash-out method (Engstrom GE)
- Plasma Cytokines [Only in the third part, measurement at baseline and at 1 hour and at 22 hours into each arm.]
Using Elisa custom kit (Qiagen) from plasma samples
- Pulmonary Cytokines [Only in the third part, measurement at baseline and at 1 hour and at 22 hours into each arm.]
Using Elisa custom kit (Qiagen) from BAL samples
- Type III Procollagen [Only in the third part, measurement at baseline and at 1 hour and at 22 hours into each arm.]
Using both RIA and Elisa methods from plasma and BAL samples
- Pulmonary Inflammatory and Fibrotic pathway [Only in the third part, measurement at baseline and at 1 hour and at 22 hours into each arm.]
Using mRNA custom kit RT-PCR analysis (Qiagen) from BAL samples
Other Outcome Measures
- Plasma Free Hemoglobin [every 24 hours, up to 72 hours.]
serum samples
- Haptoglobin [every 24 hours, up to 72 hours.]
serum samples
- Lacticodéshydrogenase (LDH) [every 24 hours, up to 72 hours.]
serum samples
- schizocytes [every 24 hours, up to 72 hours.]
serum samples
- Bilirubin [every 24 hours, up to 72 hours.]
serum samples
Eligibility Criteria
Criteria
Inclusion Criteria:
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ARDS moderate or severe (Berlin criteria)
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Onset < 48 h
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Driving pressure ≥ 11 cmH2O
Exclusion Criteria:
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Lack of consent or social protection
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Chronic respiratory failure (requiring Oxygen or NIPPV)
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Severe hypoxemia: PaO2/FIO2 < 80 with PEEP ≥ 18 cmH2O AND FIO2= 1
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Acute Renal Failure requiring RRT
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DNR order or death expected within the next 72 hours
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Planned surgery or transport out-of-ICU expected within the next 72 hours
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Heparin allergy
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Contraindication to jugular vein catheterization
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Intracranial Hypertension
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Service de REANIMATION, HOPITAL EUROPEEN MARSEILLE | Marseille | France |
Sponsors and Collaborators
- Hôpital Européen Marseille
Investigators
- Principal Investigator: Jérôme ALLARDET-SERVENT, MD, Hopital Européen Marseille
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- 2017-A03647-46