Flow-flow ECCO2-R and 4 ml/kg Tidal Volume vs. 6 ml/kg Tidal Volume to Enhance Protection From VILI in Acute Lung Injury

Flow-flow ECCO2-R and 4 ml/kg Tidal Volume vs. 6 ml/kg Tidal Volume to Enhance Protection From Ventilator Induced Lung Injury in Acute Lung Injury (ELP)

The main objective of this randomized multicenter clinical trial is to test the hypothesis that further reduction of VT to 4mL/kg may enhance lung protection in patients with ARDS as compared to the conventional "ARDS-Net" ventilation. Control of PaCO2 in the ~4 ml/kg arm would be accomplished by LFPPV- ECCO2-R.

The trial will test the hypothesis that a VT of 4 ml/kg PBW combined with low flow CO2 removal improves outcome in patients with severe ARDS (PFs ≤ 200 and PEEP ≥ 10) compared to ventilation with a VT of 6 ml/kg PBW. The study will accrue a maximum of 230 patients over approximately 12-18 months.

PRIMARY END-POINT: Number of ventilator-free days (VFDs) during the 28 days immediately after randomization

SECONDARY END-POINTS: 28 and 90-day all-cause mortality; number of ICU-free days during the 28 days immediately after randomization; cumulative incidence of: first episode of refractory hypoxemia (during 28 days after randomization), use of rescue therapies, first day that meet criteria for weaning, SOFA-free and severe adverse events.

Patients in CONTROL will be treated according to a modified, simplified version of The ARDS-Network lung protective lower tidal volume. Patients in TREATMENT group will be treated according to the ARDS-Net protocol modified (VT reduced by 1 ml/kg PBW at intervals ≤ 2 hours until VT = 4ml/kg PBW and the use of low-flow CO2 removal with a Plateau Pressure Goal: ≤ 25 cm H2O).

Inclusion Criteria:

• age > 18 years
• are on invasive assisted breathing less then 48 hours
• less than 24 hours since diagnosis for ARDS: with PF<=200 and PEEP>=10, bilateral infiltrate on chest X-Ray and no clinical evidence of left atrial hypertension
• have a commitment to full support

Exclusion Criteria:

• intubation and mechanical ventilation (any form) for > 48 hours
• risk of systemic bleeding with anticoagulation
• acute brain injury
• body mass index > 40
• neuromuscular disease that impairs ability to ventilate without assistance
• severe chronic respiratory disease
• burns > 40% total body surface area
• malignancy or other irreversible disease or condition for which 6- month mortality is estimated to be greater than 50%
• allogeneic bone marrow transplant within the last 5 years
• chronic respiratory condition making patient respirator dependent
• patient, surrogate, or physician not committed to full support
• acute myocardial infarction or acute coronary syndrome within 30 days
• moribund patient: not expected to survive 24 hours
• no consent/inability to obtain consent
• patients receiving high frequency ventilation