Acute Respiratory Distress Syndrome (ARDS)
Conditions
Keywords
ECLS, Acute Respiratory Distress Syndorme (ARDS)
Brief summary
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
PROCEDUREECLS
* 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
Sponsors
Assistance Publique - Hôpitaux de Paris
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
OTHER
Masking
NONE
Intervention model description
Multicenter, prospective, randomized, comparative open trial
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Intubation and Invasive mechanical ventilation ≤ 7 days 2. 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 3. One of the following criteria (with Vt set at 6 mL/kg PBW): * DeltaP ≥15 cm H2O OR * Ventilatory ratio ≥2.2 4. 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. 5. Social security registration (AME excluded)
Exclusion criteria
1. Age \<18 years 2. Pregnancy or breastfeeding 3. Catheter access to femoral vein or jugular vein impossible 4. Expected duration of mechanical ventilation \< 48 hours 5. Chronic restrictive or obstructive (COPD) respiratory insufficiency with home ventilation or oxygen therapy 6. Currently receiving ECLS therapy 7. Severe cardiac failure or ongoing acute coronary syndrome 8. Heparin-induced thrombocytopenia 9. Severe underlying pre-existing condition with expected six-month mortality \>50% 10. Contraindication for systemic anticoagulation (including platelet count \<50G/L) 11. Patient moribund, decision to limit therapeutic interventions 12. Acute brain injury or irreversible neurological pathology 13. Bone marrow transplantation within the last 1 year 14. Actual body weight exceeding 1 kg per centimeter of height 15. Prior enrolment in the trial
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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. | Day 30 | Each patient is compared with every other patient in the study and assigned a score (tie: 0, win: +1, loss: -1) for each pairwise comparison based on whom fared better. \- If one patient survived at day 30 and the other did not, scores of +1 and -1 will be assigned, respectively, for that pairwise comparison. If both patients in the pairwise comparison survived at day 30, the assigned score will depend on which patient had more days free from MV at day 30: the patient with more days off MV will receive a score of +1, while the patient with fewer days will receive a score of -1. If both patients survived and had the same number of days off MV, or if both patients died, they will be both assigned a score of 0 for that pairwise comparison. For each patient, scores for all pairwise comparisons will be summed, resulting in a cumulative score. |
Secondary
| Measure | Time frame |
|---|---|
| Mortality | Day 30, Day 60, Day 90 |
| Duration of mechanical ventilation | From inclusion to Day 30, from inclusion to Day 60 |
| Number of mechanical ventilation free days | Day 30, Day 60 |
| Duration of catecholamine hemodynamic support | From inclusion to Day 30, from inclusion to Day 60 |
| Number of catecholamine hemodynamic support free days | Day 30, Day 60 |
| Number of organ failure(s) free days | Day 30, Day 60 |
| Number of renal replacement therapy free days | Day 30, Day 60 |
| Durations of ICU stay | Day 90 |
| Duration of hospitalization | Day 90 |
| Proportion of patients with Pneumothorax | Day 30, Day 60 |
| Proportion of patient with rescue procedures and therapies for severe ARDS | Day 90 |
| Incidence of pump malfunction related to ECLS | Day 90 |
| Incidence of clotting related to ECLS | Day 90 |
| Incidence of air embolism related to ECLS | Day 90 |
| Incidence of hemolysis related to ECLS | Day 90 |
| Incidence of vein perforation related to ECLS | Day 90 |
| Incidence of significant bleeding (related to cannula insertion, at canula site) related to ECLS | Day 90 |
| Incidence of major hemorrhage related to ECLS | Day 90 |
| Incidence of infection at cannula site related to ECLS | Day 90 |
| Incidence of thromboembolic events related to ECLS | Day 90 |
| Incidence of stroke related to ECLS | Day 90 |
| Incidence of thrombocytopenia related to ECLS | Day 90 |
| Incidence of hypofibrinogenemia related to ECLS | Day 90 |
| Number of packed red blood cells transfused | Day 90 |
| Incidence of ventilator-associated pneumonia | From inclusion to Day 30, form inclusion to Day 60 |
| Number of days without organ failure(s), defined with the SOFA score | Day 30, Day 60 |
| Number of days without renal replacement therapy | Day 30, Day 60 |
Contacts
CONTACTAlain COMBES, Professor of medicine
Outcome results
None listed