Influence of Lung Recruitment Potential on Positive End-Expiratory Pressure (PEEP) Titration Strategies in Acute Respiratory Distress Syndrome (ARDS) Patients.

This is a prospective, randomized, open-label, parallel-group pilot study conducted at the Adult Intensive Care Unit of Hospital Dr. Franco Ravera Zunino (HFRZ). Eligible adult patients under invasive mechanical ventilation with moderate-to-severe ARDS within 36 hours of fulfilling Berlin criteria will be evaluated.

Prior to randomization, the patient's recruitment potential will be measured bedside using the R/I ratio (where > 0.5 indicates high recruitment potential and <= 0.5 indicates low potential). Eligible participants will then be randomized 1:1 into two PEEP titration groups:

• PEEP titration targeted to achieve the best static compliance of the respiratory system.
• PEEP titration guided by transpulmonary pressure measured via an esophageal balloon to target a positive end-expiratory transpulmonary pressure.

Crucially, immediately before starting the specific PEEP titration protocol in either group, an identical, standardized lung recruitment maneuver will be performed. This maneuver is executed in pressure-controlled ventilation (PCV) with a control pressure of 15 cmH2O, I:E ratio of 1:1, FiO2 1.0, starting with PEEP 5 cmH2O and increasing by 5 cmH2O every 10 seconds up to PEEP 25 cmH2O, maintaining a maximum peak pressure limit of 40 cmH2O for exactly 1 minute.

Standard baseline ventilator parameters will follow protective ventilation targets: volume-controlled ventilation, tidal volume 6-8 mL/kg of predicted body weight, respiratory rate adjusted to keep pH 7.25-7.45, plateau pressure < 28 cmH2O, and driving pressure < 14 cmH2O. Physiological parameters (PaO2/FiO2, driving pressure, ventilatory ratio, static compliance) will be recorded at 1, 24, 48, and 72 hours. The primary outcome is the change in oxygenation (PaO2/FiO2 ratio) at 24 hours. The study will explore how the baseline phenotype of lung recruitability alters early mechanical and gas exchange outcomes.

Inclusion criteria

• Diagnosis of moderate or severe Acute Respiratory Distress Syndrome (ARDS) according to the Berlin definition: acute onset, bilateral opacities not fully explained by heart failure or fluid overload, and Partial pressure of oxygen in arterial blood/Fraction of inspired oxygen <= 200 mmHg with Positive End-Expiratory Pressure (PEEP) >= 5 cmH2O.
• ARDS duration < 36 hours since fully meeting Berlin consensus criteria.
• Relative hemodynamic stability: absence of refractory shock, defined as norepinephrine dose <= 0.5 mcg/kg/min.

Exclusion criteria

• Evidence of active pulmonary air leaks (bronchopleural fistula, pneumothorax, pneumomediastinum).
• Severe uncorrected hemodynamic instability (norepinephrine > 0.5 mcg/kg/min).
• Contraindications for esophageal balloon placement (esophageal obstruction, known perforation, recent esophageal surgery, severe esophagitis).
• Elevated intracranial pressure or conditions where hypercapnia-induced increases in intracranial pressure must be avoided (intracranial hemorrhage, cerebral contusion, cerebral edema, mass effect with midline shift on CT).
• Known pregnancy.
• Severe coagulopathy (platelet count < 5,000/uL or INR > 3).
• Airway opening pressure higher than 15 cmH2O (AOP > 15 cmH2O).
• History of severe neuromuscular disease or chronic respiratory disease.
• Having received invasive mechanical ventilation for more than 96 hours.
• Inability to obtain informed consent or refusal by the legal representative.
• Contained laparotomy (open abdomen).