Acute respiratory distress syndrome (ARDS) is a severe form of respiratory failure that requires mechanical ventilation. One of the main challenges in ventilator management is selecting the optimal level of positive end-expiratory pressure (PEEP), as patients differ in their potential for lung recruitment. Individualizing PEEP may help improve lung protection by reducing lung collapse while avoiding overdistension. The study is designed to improve the understanding of bedside tools for assessing lung recruitability and to evaluate their potential role in personalizing mechanical ventilation in patients with ARDS.
Patients meeting the inclusion criteria will be enrolled in this multicenter, single-blind physiological study after informed consent has been obtained. Continuous monitoring will include electrical impedance tomography (EIT), esophageal pressure, mechanical ventilation parameters, end-tidal carbon dioxide, and standard hemodynamic monitoring throughout the study protocol.
After enrollment, a fluid responsiveness assessment will be performed using a standardized tidal volume challenge to optimize hemodynamic conditions before study interventions. Baseline measurements will then be obtained after 15 minutes at the patient's clinical ventilator settings and will include respiratory mechanics, arterial blood gases, ventilation/perfusion (V/Q) analysis, and hemodynamic variables.
The primary endpoint is the comparison between the hysteresis ratio and the recruitment-to-inflation ratio for the assessment of lung recruitability, using the reduction in lung collapse measured by EIT as the reference standard. Secondary endpoints include comparison of recruitability assessment obtained with PV loops performed at maximum inflation pressures of 40 and 30 cmH₂O, and evaluation of the physiological effects of different PEEP titration methods on respiratory mechanics, ventilation/perfusion matching, gas exchange, and hemodynamics. Clinical outcomes, including duration of mechanical ventilation, ICU and hospital length of stay, and mortality, will also be recorded.
The first study phase evaluates lung recruitability using two bedside methods: the recruitment-to-inflation (R/I) ratio and a low-flow pressure-volume loop with a maximum pressure of 40 cmH₂O (PVloop40). The order of these two assessments will be computer-randomized. During the R/I assessment, measurements will be obtained at PEEP levels of 5 and 15 cmH₂O, followed by a single-breath maneuver to calculate the recruitment-to-inflation ratio. The PVloop40 maneuver will be used to calculate the hysteresis ratio from the inspiratory and expiratory limbs of the pressure-volume curve.
Following recruitability assessment, patients will undergo a standardized lung recruitment maneuver. PEEP will be progressively increased from 5 to 24 cmH₂O with intermediate stabilization periods to assess patient tolerance. After recruitment, respiratory mechanics, arterial blood gases, and hemodynamic measurements will be repeated at the highest PEEP level.
A decremental PEEP trial will subsequently be performed from 24 to 6 cmH₂O using 2 cmH₂O decrements maintained for at least 3 minutes each. Electrical impedance tomography data obtained during this maneuver will be used to quantify regional lung collapse and overdistension and to identify the optimal PEEP according to EIT-derived criteria. After completion of the decremental trial, a second low-flow pressure-volume loop with a maximum pressure of 30 cmH₂O (PVloop30) will be performed to determine whether recruitability can be accurately assessed using lower inflation pressures.
In the final phase, participants will undergo a randomized crossover comparison of four PEEP titration strategies: (1) transpulmonary pressure-guided PEEP, (2) EIT-guided PEEP, (3) R/I ratio-guided PEEP, and (4) compliance-guided PEEP. The order of the four strategies will be computer-generated. Each PEEP strategy will be maintained for 15 minutes, followed by assessment of respiratory mechanics, ventilation/perfusion matching, and hemodynamic variables. Between interventions, patients will return to their baseline clinical PEEP for a 15-minute washout period before initiation of the next strategy.
