1) Respiratory function variables (Peak inspiratory pressure (value returned by the mechanical ventilator in cm H2O), Plateau pressure (value returned by the mechanical ventilator in cm H2O), Positive end-expiratory pressure (PEEP) (value returned by mechanical ventilator in cm H2O), Respiratory conduction pressure (Calculated as the difference between plateau pressure and PEEP. Value in cm H2O), Tidal volume (value given by the mechanical ventilation equipment in mL), Minute volume ( value given by the mechanical ventilation team in L. It is calculated as: tidal volume * respiratory frequency), Dynamic compliance (compliance) of the respiratory system (value given by the mechanical ventilation team in mL/ cm H2O. It is calculated as the volume current/ (peak inspiratory pressure – PEEP), Static compliance (compliance) of the respiratory system (value given by the mechanical ventilation team in mL/ cm H2O, It is calculated as the tidal volume/ (pressure plateau – PEEP), Total respiratory rate (value given by the mechanical ventilation equipment in breaths/minute), Mechanical power (Value measured in Joules. It is calculated: a) For volume-controlled mode: 0.098 * VC * (PIP – Pcond/2) * FR, b) For pressure-controlled mode: 0.098 * VC * (Pcond + PEEP) * FR), Index of ventilation (Calculated as follows: Ventilation rate = Respiratory rate × (Peak inspiratory pressure - PEEP) × PaCO2/ 1000)), Inspiratory fraction of oxygen (value given by the mechanical ventilation team in %). Measuring time: Daily. At baseline and until the patient is withdrawn from mechanical ventilation (up to 28 days of follow-up).
2) Gasometric variables (pH (value given by gasometry), oxygen saturation in arterial blood (value given by gasometry in %), partial pressure of oxygen in arterial blood (value given by gasometry in mm Hg), partial pressure of carbon dioxide in arterial blood (value given by blood gases in mm Hg), bicarbonate (value given by blood gases in mm Hg)). Measurement time: At the beginning and until the patient is withdrawn from invasive mechanical ventilation (up to 28 days of follow-up).
3) Radiographic evaluation of ARDS (RALE Scale (Presence of pulmonary opacities (yes or no), Type of pulmonary opacity (consolidation or ground glass pattern), RALE score according to affected areas (0 to 8 points), Other findings Measurement time: At baseline, 72 hours, 5th day, 7th day and 10th day from randomization and when clinically indicated.
4) Clinical response variables (SOFA Scale (Central Nervous System Score according to the Glasgow scale, Respiration System Score according to PaO2/FIO2 (mm Hg) value), Coagulation criteria score according to Platelet count value, Function criteria score hepatica according to total Bilirubin value (μmol/L), Cardiovascular System criteria score according to a) Mean arterial pressure value, b) Use of vasoactive drugs (dopamine, dobutamine, norepinephrine, adrenaline) (yes or no), c) Type and dose of vasoactive drugs used. Renal function criteria score according to a) Creatinine concentration in μmol/L, b) Diuresis in 24 hours in ml. SOFA scale total score value. Evaluation of organic dysfunction according to the total score). Measurement time: At baseline, 72 hours, 5th day, 7th day and 10th day from randomization. Need for vasopressor amines (Use of vasopressor amines (yes or no), Type and dose). Need for inotropic amines (yes or no, type and dose). Need for renal replacement therapy (yes or no, type and dose). ICU-acquired sepsis ((yes or no). Measurement time: from randomization. Type of sepsis). Need for endotracheal intubation in subjects with non-invasive ventilation (yes or no). ICU stay (days). Measurement time: from randomization to discharge from the ICU. Hospital stay (days in hospital). Measurement time: from randomization to discharge. Hospital mortality (Status of the subject at hospital discharge (alive or deceased), Cause of death, Place of death (inside or outside the ICU)).
5) Laboratory, molecular and cellular variables (Proinflammatory cytokines (Value of the concentration of IL-1, IL-6 and TNFα (pg/mL)). Measurement time: At the beginning, 5th day and 10th day from the randomization and when clinically indicated Inflammatory biomarkers (WBC count (x109/L), Neutrophils%, Lymphocytes%, Monocytes%, Eosinophils%, Basophils%, Platelet count (x109/L), Regulatory T cells (x109/L ), C-reactive protein (mg/L), Procalcitonin (ng/ml), Ferritin (ng/ml), Activated partial thromboplastin time, Prothrombin time, Fibrinogen (mg/L), Lactate (mmol/L), Globulins total values (g/L), LDH (U/L), quantitative D-dimer (ug/ml) Measurement time: At baseline, 5th day and 10th day from randomization and when clinically indicated Lipid profile (Value of the concentration in blood of total Cholesterol (mmol/L), Triglycerides (mmol/L), HDL-cholesterol (mmol/L), LDL-cholesterol (mmol/L)). Measurement time: At the beginning, 5th day and 10th day from randomization and when clinically indicated.
6) Safety variables (Adverse events (Yes or No), Type, Intensity (mild, moderate, severe), Severity (Serious or non-serious), Duration (start and end dates of each AE), Attitude followed before the appearance of the adverse event (it will be recorded if there were no changes or definitive interruption of treatment), Result (recovered, improved, persists or leaves sequelae), Causal relationship (very likely, probable, possible, unlikely, not related, not evaluable), Treatment indicated for the adverse event (the treatment that each patient will receive for the AE that occurs will be specified.) Measurement time: from the start of treatment until the final evaluation.
7) Control variables (Age (years), Sex (female or male), Personal pathological history (APP) (It will be collected through the dichotomous variable: Yes or No for chronic diseases such as diabetes mellitus (DM), obesity, hypertension blood pressure, dyslipidemia, ischemic heart disease, heart failure, bronchial asthma, kidney disease, Cancer, HIV/AIDS, Infection in the last 30 days (viral or bacterial) with the option of other APPs for other history), Clinical site (Name of the site clinic (hospital or Institute) to which the included patient belongs), Reason for admission to the ICU (It will be collected through the dichotomous variable: Yes or No for each of the possible causes described. If an undescribed cause is collected, it will be collected in another cause), Time from diagnosis of ARDS to randomization (hours), Risk factors for ARDS (It will be collected through the dichotomous variable: Yes or No for the most frequent causes (pneumonia, extrapulmonary sepsis, bronchial piration, non-cardiogenic shock, trauma, blood transfusion, pulmonary contusion, inhalation of toxic gases, exogenous poisoning, pulmonary vasculitis, burns, semi-drowning, COVID-19) with the option of other APPs for other history), clinical phenotype of ARDS (Clinical phenotype of ARDS will be collected in terms of cause due to trauma or non-traumatic cause, pulmonary or extrapulmonary origin, RALE Scale, Acute renal failure: yes or no), Physiological phenotype of ARDS (Physiological phenotype of ARDS will be collected as soon as a PaO2/ FiO2 ratio (light, moderate or severe), Driving pressure value, Plateau pressure value), Use of infused muscle relaxants (It will be collected through the dichotomous variable: Yes or No. In case of affirmative answer: type and dose), SAPS 3 scale (The results of the variables of each box will be collected (Box I: age, previous health condition, comorbidities, location in the hospital, and days of hospital stay and therapeutic options before admission to the ICU. Box II: reason(s) admission, anatomical location of surgery (if applicable), whether admission is planned or not, presence or suspicion of infection, and surgical condition at admission Box III: lower Glasgow scale score, higher heart rate, lower blood pressure systolic blood pressure, higher bilirubin value, higher body temperature, higher creatinine value, higher leukocyte count, lower number of platelets, lower pH value, and ventilatory and oxygenation support), Total score, Probability of death). Measurement time: Initial evaluation. Use of vasopressor amines (yes or no. Type and dose (in mg/day), Use of inotropic amines (yes or no. Type and dose (in mg/day), Use of corticosteroids (yes or no. Type and dose( in mg/ day)), Use of Sulfacen (yes or no. Type and dose (in mg/ day)), Use of diuretics (yes or no. Type and dose (in mg/ day)), Tracheostomy (yes or no ), Predicted body weight (Kg), Hospital stay prior to ICU admission (days), Type of patient (elective surgical, emergency surgical or non-surgical), ARDS presentation site (outside ICU/in ICU), Time from ICU admission to ARDS diagnosis (days), Sedation level (Richmond scale score (Score of zero (0) refers to alert and calm patients with no apparent agitation or sedation. Levels less than zero mean that the patient has a certain degree of sedation. Levels greater than zero mean that the patient has some degree of agitation), Result according to the score (Combative, Very agitated, agitated, restless, awake and calm, drowsy, mild sedation, moderate sedation, profound sedation, no response). Measurement time: At the beginning and daily until the patient is administered sedo-analgesia in infusion. Blood chemistry (Glycemia (mmol/ L), Creatinine (μmol/L), Urea (mmol/ L), Uric acid (mmol/ L), Total protein (grams/ dL), Albumin (grams/ dL), ALAT (Uts ./ L), ASAT (Uts./ L), GGT (Uts./ L), FAL (Uts./ L), Total bilirubin (μmol/L)). Measurement time: At baseline, 5th day and 10th day from randomization and when clinically indicated.
