Ultraprotective Lung Ventilation With Respiratory Extracorporeal Life Support for ARDS

Overview

Acute respiratory distress syndrome (ARDS) accounts for approximately 10% of all ICU admissions and 23% of patients requiring mechanical ventilation (MV). Despite advances in care, hospital mortality remains high, ranging from 34% in mild cases to 46% in severe ARDS. Positive-pressure MV remains the cornerstone of ARDS management. However, when excessive stress and strain are applied to the lung parenchyma, it can exacerbate lung injury, leading to ventilator-induced lung injury (VILI). VILI substantially contributes to morbidity and mortality in ARDS. Strategies that reduce tidal volume (Vt), driving pressure (ΔP, defined as plateau pressure minus PEEP), and respiratory rate (RR) can lower the mechanical power (PowerRS), i.e., the energy delivered to the lungs by the ventilator. This reduction in pulmonary stress and strain may lessen VILI and potentially improve survival. Nonetheless, reducing Vt to \<6 ml/kg in order to achieve plateau pressures \<23-25 cm H₂O, driving pressures \<9-11 cm H₂O, and RR \<15-20/min can result in severe hypercapnia. This, in turn, may increase intracranial pressure, promote pulmonary hypertension, impair myocardial contractility, reduce renal perfusion, and trigger endogenous catecholamine release. Thus, such "ultraprotective" MV strategies are not feasible for most ARDS patients managed with conventional ventilation. The neutral findings of the REST trial further suggested that low-flow extracorporeal CO₂ removal (ECCO₂R) devices may provide insufficient CO₂ clearance to enable ultraprotective ventilation while adequately controlling respiratory acidosis. Moreover, since partial lung derecruitment may occur with substantial Vt reduction, extracorporeal membrane oxygenation (ECMO) may be necessary, particularly in patients with PaO₂/FiO₂ \<120-130 at the time of Vt reduction. Therefore, respiratory extracorporeal life support (ECLS)-ranging from high-flow ECCO₂R to mid-flow venovenous ECMO (VV-ECMO)-can be employed in this setting. These modalities facilitate further reductions in ventilatory intensity while ensuring adequate oxygenation and CO₂ removal.

Interventions

• Procedure ECLS
  * ECLS catheters inserted, and EC LS initiated no later than 12h after randomization * Vt decreased to a min of 3 ml/kg PBW (by 0.5ml/kg every 30 min) to reach ΔP 9 -11 cmH2O and at least 5 cm H2O ΔP decrease * PEEP adjusted to keep the same mean airway pressure * Pump outflow set at 2-4 L/min , based on the need of blood oxygenation * RR decreased to a min of 12/min with gas flowrate adjusted to maintain PaCO2 45 mmHg. * Protocolized weaning of ECLS

Primary outcome measures

• Hierarchical criterion assessed at day 30, including all-cause mortality followed by the number of days free from MV at day 30, and calculated in such a manner that death constitutes a worse outcome than duration of ventilation. [Time frame: Day 30]

Secondary outcome measures (12)

• Mortality [Time frame: Day 30, Day 60, Day 90]
• Duration of mechanical ventilation [Time frame: From inclusion to Day 30, from inclusion to Day 60]
• Number of mechanical ventilation free days [Time frame: Day 30, Day 60]
• Duration of catecholamine hemodynamic support [Time frame: From inclusion to Day 30, from inclusion to Day 60]
• Number of catecholamine hemodynamic support free days [Time frame: Day 30, Day 60]
• Number of organ failure(s) free days [Time frame: Day 30, Day 60]
• Number of renal replacement therapy free days [Time frame: Day 30, Day 60]
• Durations of ICU stay [Time frame: Day 90]
• Duration of hospitalization [Time frame: Day 90]
• Proportion of patients with Pneumothorax [Time frame: Day 30, Day 60]
• Proportion of patient with rescue procedures and therapies for severe ARDS [Time frame: Day 90]
• Incidence of pump malfunction related to ECLS [Time frame: Day 90]

Eligibility criteria

Inclusion criteria

• Intubation and Invasive mechanical ventilation ≤ 7 days
• Presence of all of the following conditions for ≤48 hours:

• 80 ≤ PaO2/FiO2 ≤300 with PEEP >5 cmH2O
• Bilateral opacities not fully explained by effusions, lobar/lung collapse, or nodules
• Respiratory failure not fully explained by cardiac failure or fluid overload
• One of the following criteria (with Vt set at 6 mL/kg PBW):

• DeltaP ≥15 cm H2O OR
• Ventilatory ratio ≥2.2
• Signed Informed consent from a close relative or surrogate or a family member. According to the specifications of emergency inclusion, randomization without the close relative/surrogate consent could be performed if the patient is unable to give his/ger consent and when the close relative/surrogate/family member are absent. Close relative/surrogate/family member consent will be asked as soon as possible after randomization. The patient will be asked as soon as possible to give his/her consent for the continuation of the trial when his/her condition will allow.
• Social security registration (AME excluded)

Exclusion criteria

• Age <18 years
• Pregnancy or breastfeeding
• Catheter access to femoral vein or jugular vein impossible
• Expected duration of mechanical ventilation < 48 hours
• Chronic restrictive or obstructive (COPD) respiratory insufficiency with home ventilation or oxygen therapy
• Currently receiving ECLS therapy
• Severe cardiac failure or ongoing acute coronary syndrome
• Heparin-induced thrombocytopenia
• Severe underlying pre-existing condition with expected six-month mortality >50%
• Contraindication for systemic anticoagulation (including platelet count <50G/L)
• Patient moribund, decision to limit therapeutic interventions
• Acute brain injury or irreversible neurological pathology
• Bone marrow transplantation within the last 1 year
• Actual body weight exceeding 1 kg per centimeter of height
• Prior enrolment in the trial

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Other

Study locations

Center list to be confirmed — check the primary protocol.

Identifiers

NCT: NCT07516665 · APHP240924 · IDRCB number

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗