Effects on Biotrauma of NMBAs and PP Association During ARDS
- Conditions
- Moderate to Severe Acute Respiratory Distress Syndrome
- Interventions
- Drug: NMBAsOther: Prone positioning
- Registration Number
- NCT06212492
- Lead Sponsor
- Assistance Publique Hopitaux De Marseille
- Brief Summary
The improved survival of patients with acute respiratory distress syndrome (ARDS) over the last decades is related to the use of so-called "protective" mechanical ventilation. Two therapies have been shown to increase survival among the most hypoxemic patients (PaO2/FiO2 \< 150 mmHg): a continuous use of neuromuscular blocking agents (NMBAs) for 48 hours in the acute phase of ARDS and prone positioning (PP). NMBAs and PP are part of the latest guidelines from French ICU Society. However, North American guidelines recommend PP for patients with severe ARDS only but not NMBAs, given the results of the ROSE study which did not confirm the benefit on mortality demonstrated in the ACURASYS study. However, in the ROSE study, ventilatory strategy, use of NMBAs and PP were different from the ACURASYS study.
Yet, NMBAs and PP are frequently associated in clinical practice, particularly with the COVID-19 pandemic, but also in randomized trials. In the PROSEVA study, almost all the patients (91%) received a continuous infusion of NMBAs during PP. Indeed, there is a common physiopathological rationale in both techniques: they favor the homogenization of transpulmonary pressures (TPP), reduce lung overdistension, Pendelluft effect and thus ventilator induced lung injury (VILI), in particular barotrauma and biotrauma. This reduction of biotrauma has been demonstrated for PP and NMBAs separately, but never by comparing the combined effect of the 2 techniques to each of them separately. This comparison requires reliable tools. In recent years, the "soluble form of the receptor for advanced glycation end products" (sRAGE), a new biomarker specific of pulmonary epithelial aggression and therefore of biotrauma, has been described and evaluated during ARDS and appears to be associated with the severity of pulmonary damage and prognosis.
Overall, despite an interesting physiopathological rationale and a clinically widespread practice, there is currently no study evaluating the synergistic effect of PP and NMBAs in the treatment of ARDS, in particular on the prevention of VILI, and more precisely of biotrauma. This question seems crucial to better specify the respective place of each of these treatments in the management strategy of ARDS patients whose prevalence and mortality remain high.
The objective of this study is therefore to evaluate, using a recent and reliable biomarker, the synergistic effect of a short-term NMBAs infusion using cisatracurium and PP on the reduction of biotrauma during moderate to severe ARDS. The investigators will compare this "synergistic" treatment to the use of PP alone. They will also evaluate, in secondary objectives, the effects of PP and NMBAs combination on clinical outcomes and on the patients' prognosis.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 40
- Age > 18 years
- Written informed consent of proxy to the study participation
- Invasive mechanical ventilation for ≤ 72 hours at inclusion
- Criteria of moderate to severe ARDS according to the Berlin definition
- Patients covered by or having the rights to social security
- Pregnant or breast-feeding women, patients deprived of freedom or under legal authority
- Patients having undergone previous PP sessions during the same stay
- Patients who had already been curarized prior to inclusion
- Patient currently receiving ECMO or any technique of extracorporeal CO2 removal at the time of inclusion
- Patient with a contraindication to PP
- Previous hypersensitivity or anaphylactic reaction to any NMBA
- Chronic respiratory insufficiency with oxygen or long-term ventilation
- SAPS II score at the time of enrollment > 75
- Patients who are moribund or for whom limitations of active therapies have been decided.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Prone Positioning and NMBAs (PP-NMBAs) NMBAs Early and systematic use of Prone positioning and NMBAs Prone Positioning and NMBAs (PP-NMBAs) Prone positioning Early and systematic use of Prone positioning and NMBAs Prone Positioning (PP) Prone positioning Early and systematic use of prone positioning with NMBAs indicated ONLY as rescue
- Primary Outcome Measures
Name Time Method Difference between the plasma sRAGE value at the end of the first PP session and the baseline value before PP (∆ sRAGE). Day 1 Our primary outcome will be the comparison of the differences in plasma sRAGE levels before and after the first PP session (∆ sRAGE), a kinetic being probably more relevant than a raw value, given the observed inter-individual variations of sRAGE at basal state.
- Secondary Outcome Measures
Name Time Method Plasma determination of IL1 before the first PP session Day 1 Inflammation, pulmonary epithelial and endothelial dysfunction
Plasma determination of IL1 1 hour after PP initiation at the first PP session Day 1 Inflammation, pulmonary epithelial and endothelial dysfunction
Plasma determination of IL1 4 hours after return to supine after the first PP session Day 2 Inflammation, pulmonary epithelial and endothelial dysfunction
Positive Expiratory Pressure (PEEP) 6 hours after PP initiation at each PP session Up to Day 28 Protective mechanical ventilation
Positive Expiratory Pressure (PEEP) at the end of each PP session Up to Day 28 Protective mechanical ventilation
Plateau pressure (Pplat) 72 hours after inclusion 72 hours after inclusion Protective mechanical ventilation
Plasma determination of TNFα before the first PP session Day 1 Inflammation, pulmonary epithelial and endothelial dysfunction
Positive Expiratory Pressure (PEEP) 1 hour after PP initiation at each PP session Up to Day 28 Protective mechanical ventilation
Plasma determination of IL1 at the end of the first PP session Day 1 Inflammation, pulmonary epithelial and endothelial dysfunction
Plasma determination of TNFα 1 hour after PP initiation at the first PP session Day 1 Inflammation, pulmonary epithelial and endothelial dysfunction
Plasma determination of TNFα at the end of the first PP session Day 1 Inflammation, pulmonary epithelial and endothelial dysfunction
Plasma determination of TNFα 4 hours after return to supine after the first PP session Day 2 Inflammation, pulmonary epithelial and endothelial dysfunction
Plasma determination of sRAGE before the first PP session Day 1 Inflammation, pulmonary epithelial and endothelial dysfunction
Plasma determination of sRAGE 1 hour after PP initiation at the first PP session Day 1 Inflammation, pulmonary epithelial and endothelial dysfunction
Plasma determination of sRAGE at the end of the first PP session Day 1 Inflammation, pulmonary epithelial and endothelial dysfunction
Plasma determination of sRAGE 4 hours after return to supine after the first PP session Day 2 Inflammation, pulmonary epithelial and endothelial dysfunction
Plasma determination of angiopoietin 2 before the first PP session Day 1 Inflammation, pulmonary epithelial and endothelial dysfunction
Plasma determination of angiopoietin 2 1 hour after PP initiation at the first PP session Day 1 Inflammation, pulmonary epithelial and endothelial dysfunction
Plasma determination of angiopoietin 2 at the end of the first PP session Day 1 Inflammation, pulmonary epithelial and endothelial dysfunction
Hospital mortality At Day 90 Plasma determination of angiopoietin 2 4 hours after return to supine after the first PP session Day 2 Inflammation, pulmonary epithelial and endothelial dysfunction
PaO2/FiO2 before each PP session Up to Day 28 Hematosis
PaO2/FiO2 1 hour after PP initiation at each PP session Up to Day 28 Hematosis
PaO2/FiO2 6 hours after PP initiation at each PP session Up to Day 28 Hematosis
PaO2/FiO2 at the end of each PP session Up to Day 28 Hematosis
PaO2/FiO2 4 hours after return to supine after each PP session Up to Day 28 Hematosis
PaO2/FiO2 48 hours after inclusion 48 hours after inclusion Hematosis
PaO2/FiO2 72 hours after inclusion 72 hours after inclusion Hematosis
PaO2/FiO2 7 days after inclusion 7 days after inclusion Hematosis
pH before each PP session Up to Day 28 Hematosis
pH 1 hour after PP initiation at each PP session Up to Day 28 Hematosis
pH 6 hours after PP initiation at each PP session Up to Day 28 Hematosis
pH at the end of each PP session Up to Day 28 Hematosis
pH 4 hours after return to supine after each PP session Up to Day 28 Hematosis
pH 48 hours after inclusion 48 hours after inclusion Hematosis
pH 72 hours after inclusion 72 hours after inclusion Hematosis
pH 7 days after inclusion 7 days after inclusion Hematosis
PaCO2 before each PP session Up to Day 28 Hematosis
PaCO2 1 hour after PP initiation at each PP session Up to Day 28 Hematosis
PaCO2 6 hours after PP initiation at each PP session Up to Day 28 Hematosis
PaCO2at the end of each PP session Up to Day 28 Hematosis
PaCO2 4 hours after return to supine after each PP session Up to Day 28 Hematosis
PaCO2 48 hours after inclusion 48 hours after inclusion Hematosis
PaCO2 72 hours after inclusion 72 hours after inclusion Hematosis
PaCO2 7 days after inclusion 7 days after inclusion Hematosis
Plateau pressure (Pplat) before each PP session Up to Day 28 Protective mechanical ventilation
Plateau pressure (Pplat) 1 hour after PP initiation at each PP session Up to Day 28 Protective mechanical ventilation
Plateau pressure (Pplat) 6 hours after PP initiation at each PP session Up to Day 28 Protective mechanical ventilation
Plateau pressure (Pplat) at the end of each PP session Up to Day 28 Protective mechanical ventilation
Plateau pressure (Pplat) 48 hours after inclusion 48 hours after inclusion Protective mechanical ventilation
Ventilator free days (VFD) At Day 90 Positive Expiratory Pressure (PEEP) 48 hours after inclusion 48 hours after inclusion Protective mechanical ventilation
Positive Expiratory Pressure (PEEP) 7 days after inclusion 7 days after inclusion Protective mechanical ventilation
Driving Pressure (Δp) before each PP session Up to Day 28 Protective mechanical ventilation
Positive Expiratory Pressure (PEEP) 72 hours after inclusion 72 hours after inclusion Protective mechanical ventilation
Plateau pressure (Pplat) 4 hours after return to supine after each PP session Up to Day 28 Protective mechanical ventilation
Plateau pressure (Pplat) 7 days after inclusion 7 days after inclusion Protective mechanical ventilation
Transpulmonary pressure (TPP) (for equipped sites) at the end of each PP session Up to Day 28 Alveolar recruitment
Electrical Impedance Tomography data (for equipped sites) before each PP session Up to Day 28 Alveolar recruitment
Electrical Impedance Tomography data (for equipped sites) 1 hour after PP initiation at each PP session Up to Day 28 Alveolar recruitment
Electrical Impedance Tomography data (for equipped sites) at the end of each PP session Up to Day 28 Alveolar recruitment
Pneumothorax Within the first 7 days Barotrauma
Pneumomediastinum Within the first 7 days Barotrauma
Sub cutaneous emphysema Within the first 7 days Barotrauma
Number of days alive without extra-respiratory organ failure At Day 90 Length of stay in intensive care unit Maximum 3 months after inclusion (follow-up duration) Length of hospital stay Maximum 3 months after inclusion (follow-up duration) Medical Research Council (MRC) At day 28 or discharge Positive Expiratory Pressure (PEEP) before each PP session Up to Day 28 Protective mechanical ventilation
Positive Expiratory Pressure (PEEP) 4 hours after return to supine after each PP session Up to Day 28 Protective mechanical ventilation
Driving Pressure (Δp) 1 hour after PP initiation at each PP session Up to Day 28, Protective mechanical ventilation
Driving Pressure (Δp) 6 hours after PP initiation at each PP session Up to Day 28 Protective mechanical ventilation
Driving Pressure (Δp) at the end of each PP session Up to Day 28 Protective mechanical ventilation
Driving Pressure (Δp) 4 hours after return to supine after each PP session Up to Day 28 Protective mechanical ventilation
Driving Pressure (Δp) 48 hours after inclusion 48 hours after inclusion Protective mechanical ventilation
Driving Pressure (Δp) 72 hours after inclusion 72 hours after inclusion Protective mechanical ventilation
Driving Pressure (Δp) 7 days after inclusion 7 days after inclusion Protective mechanical ventilation
Tidal Volume (Vt) before each PP session Up to Day 28 Protective mechanical ventilation
Tidal Volume (Vt) 1 hour after PP initiation at each PP session Up to Day 28 Protective mechanical ventilation
Tidal Volume (Vt) 6 hours after PP initiation at each PP session Up to Day 28 Protective mechanical ventilation
Esophageal pressure (for equipped sites) at the end of each PP session Up to Day 28 Alveolar recruitment
Transpulmonary pressure (TPP) (for equipped sites) before each PP session Up to Day 28 Alveolar recruitment
Transpulmonary pressure (TPP) (for equipped sites) 1 hour after PP initiation at each PP session Up to Day 28 Alveolar recruitment
Tidal Volume (Vt) at the end of each PP session Up to Day 28 Protective mechanical ventilation
Tidal Volume (Vt) 48 hours after inclusion 48 hours after inclusion Protective mechanical ventilation
Respiratory Rate (Fr) before each PP session Up to Day 28 Protective mechanical ventilation
Respiratory Rate (Fr) 6 hours after PP initiation at each PP session Up to Day 28 Protective mechanical ventilation
Respiratory Rate (Fr) at the end of each PP session Up to Day 28 Protective mechanical ventilation
Respiratory Rate (Fr) 4 hours after return to supine after each PP session Up to Day 28 Protective mechanical ventilation
Respiratory Rate (Fr) 48 hours after inclusion 48 hours after inclusion Protective mechanical ventilation
Respiratory Rate (Fr) 72 hours after inclusion 72 hours after inclusion Protective mechanical ventilation
Respiratory Rate (Fr) 7 days after inclusion 7 days after inclusion Protective mechanical ventilation
Esophageal pressure (for equipped sites) before each PP session Up to Day 28 Alveolar recruitment
Esophageal pressure (for equipped sites) 1 hour after PP initiation at each PP session Up to Day 28 Alveolar recruitment
Tidal Volume (Vt) 4 hours after return to supine after each PP session Up to Day 28 Protective mechanical ventilation
Tidal Volume (Vt) 72 hours after inclusion 72 hours after inclusion Protective mechanical ventilation
Tidal Volume (Vt) 7 days after inclusion 7 days after inclusion Protective mechanical ventilation
Respiratory Rate (Fr) 1 hour after PP initiation at each PP session Up to Day 28 Protective mechanical ventilation
Trial Locations
- Locations (1)
Service Médecine Intensive et Réanimation
🇫🇷Marseille, France