Physiological Effects of Controlled vs. Assisted Ventilation During Moderate-to-severe Acute Respiratory Distress Syndrome (PEARL Study)

This is a prospective, single center, physiological interventional study designed to investigate the respiratory mechanics and regional lung ventilation effects of assisted versus fully controlled mechanical ventilation in patients with moderate to severe acute respiratory distress syndrome (ARDS). The study is conducted in a tertiary care intensive care unit and focuses on short term physiological responses to different ventilatory strategies under controlled experimental conditions. The study specifically evaluates how ventilation mode and tidal volume targeting influence regional lung inflation, inspiratory effort, and risk of ventilator induced lung injury using advanced physiological monitoring tools, including esophageal pressure measurement and electrical impedance tomography.

The scientific rationale is based on the observation that assisted ventilation modes, such as pressure support ventilation, preserve spontaneous breathing but may expose patients with high respiratory drive to excessive tidal volumes and transpulmonary pressures. This condition is associated with patient self inflicted lung injury and regional lung overdistension. Fully controlled ventilation allows strict control of tidal volume and driving pressure and may reduce regional lung stress and strain. However, direct physiological comparison between assisted and controlled ventilation under standardized conditions remains limited. This study evaluates whether switching patients with high inspiratory effort to volume controlled ventilation, either maintaining tidal volume observed during assisted ventilation or targeting protective driving pressure values, improves regional ventilation homogeneity and reduces markers of lung overdistension while preserving gas exchange.

After enrollment, patients undergo four sequential ventilatory phases applied in a fixed order. Each phase lasts 30 minutes. The first 25 minutes allow physiological stabilization and adaptation to the ventilatory mode. The final 5 minutes are used for signal acquisition and physiological measurements. The four phases include assisted ventilation with clinically selected pressure support and positive end expiratory pressure, volume controlled ventilation targeting 6 ml per kg predicted body weight, volume controlled ventilation with tidal volume matched to tidal volume measured during assisted ventilation with neuromuscular blockade, and volume controlled ventilation targeting 6 ml per kg predicted body weight with neuromuscular blockade and driving pressure titration to remain at or below 14 cmH2O. During neuromuscular blockade phases, respiratory rate is adjusted based on arterial blood gas analysis to maintain physiological pH and PaCO2 targets.

Respiratory mechanics are assessed using combined airway, esophageal, and gastric pressure measurements obtained through a balloon catheter nasogastric tube system. Flow and airway pressure are measured using a pneumotachograph. Signals are acquired digitally and stored for offline analysis. Derived parameters include inspiratory effort, transpulmonary pressure swings, respiratory system and lung driving pressure, lung and chest wall compliance, respiratory muscle activity, pressure time product, and occlusion pressure indices. Static respiratory mechanics are assessed using standardized inspiratory and expiratory occlusion maneuvers. These measurements allow detailed characterization of patient ventilator interaction, lung stress, and mechanical energy transfer to the respiratory system.

Regional ventilation distribution is assessed using electrical impedance tomography. A dedicated electrode belt positioned at the mid thoracic level continuously records impedance changes at high temporal resolution. Offline analysis includes calculation of tidal ventilation distribution between dependent and nondependent lung regions, estimation of regional tidal volume, ventilation homogeneity indices, pixel level ventilation heterogeneity, end expiratory lung impedance changes, and detection of pendelluft phenomenon. Recruitment volume is estimated by comparing end expiratory impedance at different positive end expiratory pressure levels. These measurements provide high resolution functional imaging of regional lung aeration and ventilation distribution during each ventilatory phase.