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

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.

Inclusion criteria

• Adult patient (age ≥ 18 years)
• Patient hospitalized in the Intensive Care Unit (ICU) for acute respiratory distress syndrome (according to the Berlin definition), requiring invasive mechanical ventilation with deep sedation and controlled mechanical ventilation mode
• Patient or next of kin informed about the study and not objecting to participation

Exclusion criteria

• Undrained pneumothorax or any contraindication to a transient increase in airway pressure
• Known or suspected intracranial hypertension
• Patient under legal protection (e.g., guardianship)
• Not affiliated with a social security system
• Presence of spontaneous respiratory effort
• Presence of a leak in the ventilatory circuit
• Hemodynamic instability (e.g., uncontrolled shock, increasing vasopressor requirement)
• Uncontrolled severe hypoxemia
• Undrained pneumothorax or any contraindication to a transient increase in airway pressure
• Known or suspected intracranial hypertension