Assessment of the Reproducibility of the Recruitment-to-inflation Ratio (R/I Ratio) Measurement in Patients With Acute Respiratory Distress Syndrome

Overview

Acute respiratory distress syndrome (ARDS) is a severe lung condition that often requires invasive mechanical ventilation in the intensive care unit. In these patients, setting the ventilator appropriately is essential to improve oxygenation while limiting ventilator-induced lung injury. One important ventilator setting is positive end-expiratory pressure (PEEP), which helps keep the lungs open. However, the optimal PEEP level may vary from one patient to another. The recruitment-to-inflation ratio (R/I ratio) is a bedside measurement used to estimate the potential for lung recruitment during a decrease in PEEP. It compares the compliance of the lung volume recruited by PEEP with the compliance of the already aerated lung. A higher R/I ratio suggests that increasing PEEP is more likely to reopen collapsed lung units, whereas a lower R/I ratio suggests limited recruitability and a higher likelihood that additional pressure would mainly distend lung areas that are already open. In clinical practice, the R/I ratio is increasingly used to guide PEEP adjustment, with the aim of improving recruitment and oxygenation while avoiding unnecessary increases in airway pressure. However, although the R/I ratio is used in routine care, there are currently no data demonstrating that this measurement is reproducible when repeated in the same patient under similar conditions. The hypothesis of this study is that the R/I ratio is reproducible when measured twice in the same patient under stable conditions, including no significant changes in ventilator settings, hemodynamic status, or ongoing treatments. This prospective, multicenter, non-interventional study will include adult ICU patients with ARDS who are receiving invasive mechanical ventilation, deep sedation, and assist-control ventilation. For each patient, airway opening pressure will be assessed, and the R/I ratio will be measured twice on the same day by a trained clinician, between 20 and 120 minutes apart, without changes in ventilator settings or treatments likely to influence the measurement. The main objective is to evaluate the within-patient reproducibility of the R/I ratio. Secondary objectives include describing changes in airway opening pressure and R/I ratio over time, assessing the reproducibility of expired tidal volume during the maneuvers, and evaluating the clinical tolerance of these ventilatory measurements. The study will include 80 patients across 4 French intensive care units. No additional intervention outside routine care will be performed. Clinical, ventilatory, and biological data already collected as part of usual care will be recorded.

Acute respiratory distress syndrome (ARDS) is a severe form of acute respiratory failure requiring invasive mechanical ventilation. Lung-protective ventilation strategies, including the adjustment of positive end-expiratory pressure (PEEP), are central to management but remain challenging due to inter-individual variability in lung recruitability and mechanics. The recruitment-to-inflation ratio (R/I) is a bedside physiological measurement used to estimate the potential for lung recruitment following a change in PEEP. It reflects the proportion of volume gain attributable to recruitment of previously non-aerated lung regions, as opposed to inflation of already aerated lung ("baby lung"). In clinical practice, this parameter is used in some centers to help guide PEEP selection, with the aim of avoiding unnecessary PEEP increases in patients with low recruitability, which may expose them to lung overdistension. In parallel, the measurement of airway opening pressure (AOP) allows identification of airway closure and may help optimize ventilator settings. Although R/I ratio and AOP measurements are increasingly used in routine care, no data are currently available regarding the reproducibility of the R/I ratio when measured repeatedly in the same patient under stable conditions. Assessing this reproducibility is essential to determine whether observed variations reflect true physiological changes or measurement variability. This is a prospective, multicenter, non-interventional study conducted in four French intensive care units where R/I ratio and AOP measurements are part of routine clinical practice. Adult patients with ARDS receiving invasive mechanical ventilation under deep sedation and assist-control mode will be included. For each patient, AOP will be assessed using a standardized low-flow inflation maneuver. The R/I ratio will be measured using a standardized PEEP step maneuver, consisting of a decrease in PEEP from a high level (typically 15 cmH₂O) to a lower level (typically 5 cmH₂O or adjusted to AOP when present), with measurement of the resulting expired volume. The recruited volume is calculated as the difference between measured expired volume and predicted volume based on compliance at low PEEP, allowing computation of the R/I ratio. These procedures follow standardized methods routinely used in participating centers. Two R/I measurements (T1 and T2) will be performed in each patient on the same day, 20 to 120 minutes apart, by the same trained clinician. Measurements will be conducted under strictly stable conditions, including no significant changes in ventilator settings, hemodynamic status, patient position, or ongoing treatments. Predefined stability criteria include limited variation in vasopressor dose, arterial pressure, heart rate, oxygenation, and ventilator parameters. Clinical, ventilatory, and biological data routinely collected as part of standard care will be recorded. Data will be entered into a secure electronic case report form (eCRF) using REDCap. Data collection is prospective, with pseudonymization of patient identifiers. Data quality will be ensured through predefined data entry checks in the eCRF, including range checks and consistency checks across variables. Source data verification may be performed by comparing eCRF entries with medical records when necessary. Investigators involved in the study are trained in both the measurement techniques and data collection procedures. The primary objective is to assess intra-patient reproducibility of the R/I ratio. Reproducibility will be evaluated using an intraclass correlation coefficient (ICC, two-way mixed-effects model, absolute agreement). Secondary analyses include assessment of absolute and relative differences between measurements, reproducibility of expired tidal volume during maneuvers, longitudinal evolution of R/I and AOP during ICU stay, and clinical tolerance of the procedures. The sample size is based on the precision of the ICC estimate. A total of 61 patients are required to estimate an ICC of 0.90 with a precision of 10%. To account for potential missing or non-analyzable data, 80 patients will be included. Missing data will not be imputed and will be described. Analyses will be performed on available data under conditions where measurement validity criteria are met. Statistical analyses will include descriptive statistics and appropriate comparative tests depending on data distribution. Reproducibility will be assessed using ICC, and agreement between measurements will also be explored using absolute and relative differences. This study does not involve any intervention beyond routine care. The results are expected to provide important information on the reliability of R/I measurement and support its appropriate use in clinical practice.