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

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Acute Respiratory Distress Syndrome (ARDS)

Detailed Description

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.

• Study Type: Observational
• Enrollment (Estimated): 80

Contacts and Locations

• Study Contact: Name: Tai PHAM; Phone Number: +33 145217245; Email: tai.pham@aphp.fr
• Study Contact Backup: Name: Nicolas BIARD; Email: nicolasbiard.bl@gmail.com

Study Locations

• France
  • Créteil, France
    • Hôpital Henri Mondor
    • Contact: Guilluame CARTEAUX; Phone Number: +33 1 49 81 43 76; Email: guillaume.carteaux@aphp.fr
  • Le Kremlin-Bicêtre, France
    • Hôpital Bicêtre
    • Contact: Tai PHAM; Phone Number: +33145217245; Email: tai.pham@aphp.fr
    • Contact: Nicolas BIARD; Email: nicolasbiard.bl@gmail.com
  • Paris, France
    • Hopital Saint-Antoine
    • Contact: Vincent BONNY; Phone Number: +331 49 28 21 45; Email: vincent.bonny@aphp.fr
  • Paris, France
    • Hôpital La Pitié-Salpétrière
    • Contact: Martin DRES; Phone Number: +331 42 16 38 31; Email: martin.dres@aphp.fr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Adult patients admitted to intensive care units in participating centers for acute respiratory distress syndrome and requiring invasive mechanical ventilation will be screened for inclusion. The study population will be drawn from routine clinical practice in four French academic intensive care units where airway opening pressure and recruitment-to-inflation ratio measurements are performed as part of standard care in selected patients with moderate to severe disease.

Description

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

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Intraclass Correlation Coefficient of the Recruitment-to-Inflation Ratio (R/I)	Intra-patient reproducibility of the recruitment-to-inflation ratio (R/I) assessed using an intraclass correlation coefficient (ICC, two-way mixed-effects model, absolute agreement) between two measurements (T1 and T2) performed under stable clinical conditions.	Same day as inclusion, between 20 and 120 minutes between the two measurements

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Absolute and relative difference in recruitment-to-inflation ratio (R/I) between two measurements (T1 and T2)	Absolute (ΔR/I) and relative (%) difference in the recruitment-to-inflation ratio (R/I) between two measurements (T1 and T2) performed under stable clinical conditions.	Same day as inclusion, between 20 and 120 minutes between the two measurements
Intra-patient reproducibility and variability of expired tidal volume (Vte)	Intra-patient reproducibility of expired tidal volume (Vte) assessed using an intraclass correlation coefficient (ICC, two-way mixed-effects model, absolute agreement), as well as absolute and relative (%) differences between two measurements (T1 and T2).	Same day as inclusion, between 20 and 120 minutes between the two measurements
Longitudinal evolution of recruitment-to-inflation ratio (R/I)	Temporal evolution of the recruitment-to-inflation ratio (R/I) and airway opening pressure (AOP) assessed using repeated measurements during the ICU stay	From inclusion up to ICU discharge (maximum 28 days)
Longitudinal evolution of airway opening pressure (AOP)	Temporal evolution of airway opening pressure (AOP) assessed using repeated measurements when available during the ICU stay	From inclusion until ICU discharge (up to 28 days)
Incidence of adverse events during ventilatory measurement procedures	Occurrence of adverse events during or immediately after R/I or AOP measurement procedures, including oxygen desaturation (≥5% decrease or SpO₂ ≤85%), hemodynamic instability requiring increased vasopressors, new or worsening arrhythmia, or premature interruption of the maneuver.	Periprocedural (from initiation to immediate completion of each R/I or AOP measurement procedure), assessed during the ICU stay (up to 28 days)

Collaborators and Investigators

• Sponsor: Assistance Publique - Hôpitaux de Paris

Study record dates

Study Major Dates

• Study Start (Estimated): June 30, 2026
• Primary Completion (Estimated): June 30, 2027
• Study Completion (Estimated): June 30, 2027

Study Registration Dates

• First Submitted: June 1, 2026
• First Submitted That Met QC Criteria: June 22, 2026
• First Posted (Actual): June 24, 2026

Study Record Updates

• Last Update Posted (Actual): June 24, 2026
• Last Update Submitted That Met QC Criteria: June 22, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: Mechanical Ventilation; Reproducibility of Results; Respiratory Mechanics; Airway Opening Pressure; Positive End-Expiratory Pressure; Lung Recruitment; Lung Recruitability; Intraclass Correlation Coefficient
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Lung Diseases; Respiration Disorders; Respiratory Distress Syndrome
• Other Study ID Numbers: APHP251877; 2025-A02834-45 (Other Identifier: IDRCB)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No