Ultraprotective Lung Ventilation With Respiratory Extracorporeal Life Support for ARDS
试验速览
- 阶段
- 不适用
- 状态
- 尚未招募
- 入组人数
- 290
- 主要终点
- 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.
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Other
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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)
排除标准
- •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
研究组 & 干预措施
Expérimental : ECLS
- ECLS catheter s 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 cm H2O and at least 5 cm H 2 O 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 flow rate adjusted to maintain PaCO2 45 mmHg.
- Protocolized weaning of ECLS
干预措施: ECLS (Procedure)
Control : Conventional Treatment Arm
-
Conventional management of ARDS
-
Ventilatory settings:
-
Volume assist control mode,
-
VT 6 ml/kg of predicted body weight
-
PEEP adjusted for Pplateau 28 29 cmH2O ;
-
FiO2 for 88%≤SaO2≤95% or 55 mmHg≤PaO2≤80 mm Hg
-
RR up to 35/mn, for a PaCO2 resulting in 7.30<pH<7.42
结局指标
主要结局
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.
时间窗: 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.
次要结局
- Number of organ failure(s) free days(Day 30, Day 60)
- 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 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)