Influence of Lung Recruitment Potential on PEEP Titration Strategies in ARDS Patients. (RECRUIT-PEEP)

Influence of the Lung Recruitment Potential on the Response to Two PEEP Titration Strategies in Patients With Acute Respiratory Distress Syndrome (ARDS)

Acute Respiratory Distress Syndrome (ARDS) is characterized by severe hypoxemia and diffuse alveolar collapse, often requiring invasive mechanical ventilation. Non-individualized mechanical ventilation settings can cause ventilator-induced lung injury (VILI). Positive end-expiratory pressure (PEEP) prevents alveolar collapse, but its effect varies among individuals. The recruitment-to-inflation (R/I) ratio evaluates bedside lung recruitment potential. This pilot study aims to compare two individualized PEEP titration strategies-one guided by the best static respiratory compliance and another guided by transpulmonary pressure via an esophageal balloon-and evaluate how baseline lung recruitment potential alters the early physiological responses to these interventions. Both strategies are preceded by an identical, standardized pressure-controlled initial lung recruitment maneuver to establish a baseline recruitment state.

Study Overview

• Status: Not yet recruiting
• Conditions: ARDS (Acute Respiratory Distress Syndrome)
• Intervention / Treatment: Procedure: PEEP Titration guided by Static Compliance; Procedure: PEEP Titration guided by Transpulmonary Pressure

Detailed Description

This is a prospective, randomized, open-label, parallel-group pilot study conducted at the Adult Intensive Care Unit of Hospital Dr. Franco Ravera Zunino (HFRZ). Eligible adult patients under invasive mechanical ventilation with moderate-to-severe ARDS within 36 hours of fulfilling Berlin criteria will be evaluated.

Prior to randomization, the patient's recruitment potential will be measured bedside using the R/I ratio (where > 0.5 indicates high recruitment potential and <= 0.5 indicates low potential). Eligible participants will then be randomized 1:1 into two PEEP titration groups:

1. PEEP titration targeted to achieve the best static compliance of the respiratory system.
2. PEEP titration guided by transpulmonary pressure measured via an esophageal balloon to target a positive end-expiratory transpulmonary pressure.

Crucially, immediately before starting the specific PEEP titration protocol in either group, an identical, standardized lung recruitment maneuver will be performed. This maneuver is executed in pressure-controlled ventilation (PCV) with a control pressure of 15 cmH2O, I:E ratio of 1:1, FiO2 1.0, starting with PEEP 5 cmH2O and increasing by 5 cmH2O every 10 seconds up to PEEP 25 cmH2O, maintaining a maximum peak pressure limit of 40 cmH2O for exactly 1 minute.

Standard baseline ventilator parameters will follow protective ventilation targets: volume-controlled ventilation, tidal volume 6-8 mL/kg of predicted body weight, respiratory rate adjusted to keep pH 7.25-7.45, plateau pressure < 28 cmH2O, and driving pressure < 14 cmH2O. Physiological parameters (PaO2/FiO2, driving pressure, ventilatory ratio, static compliance) will be recorded at 1, 24, 48, and 72 hours. The primary outcome is the change in oxygenation (PaO2/FiO2 ratio) at 24 hours. The study will explore how the baseline phenotype of lung recruitability alters early mechanical and gas exchange outcomes.

• Study Type: Interventional
• Enrollment (Estimated): 52
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Esteban Santis, RT.; Phone Number: +56 940367716; Email: esteban.santis@ogb.cl
• Study Contact Backup: Name: Hospital Dr. Franco Ravera Zunino; Phone Number: +56 729383; Email: carolina.lindsay.brain@gmail.com

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Diagnosis of moderate or severe Acute Respiratory Distress Syndrome (ARDS) according to the Berlin definition: acute onset, bilateral opacities not fully explained by heart failure or fluid overload, and PaO2/FiO2 <= 200 mmHg with PEEP >= 5 cmH2O.
• ARDS duration < 36 hours since fully meeting Berlin consensus criteria.
• Relative hemodynamic stability: absence of refractory shock, defined as norepinephrine dose <= 0.5 mcg/kg/min.

Exclusion Criteria:

• Evidence of active pulmonary air leaks (bronchopleural fistula, pneumothorax, pneumomediastinum).
• Severe uncorrected hemodynamic instability (norepinephrine > 0.5 mcg/kg/min).
• Contraindications for esophageal balloon placement (esophageal obstruction, known perforation, recent esophageal surgery, severe esophagitis).
• Elevated intracranial pressure or conditions where hypercapnia-induced increases in intracranial pressure must be avoided (intracranial hemorrhage, cerebral contusion, cerebral edema, mass effect with midline shift on CT).
• Known pregnancy.
• Severe coagulopathy (platelet count < 5,000/uL or INR > 3).
• Airway opening pressure higher than 15 cmH2O (AOP > 15 cmH2O).
• History of severe neuromuscular disease or chronic respiratory disease.
• Having received invasive mechanical ventilation for more than 96 hours.
• Inability to obtain informed consent or refusal by the legal representative.
• Contained laparotomy (open abdomen).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Best Static Compliance Titration; Patients receive positive end-expiratory pressure (PEEP) titration guided by the best static compliance of the respiratory system after undergoing a standardized initial lung recruitment maneuver	Procedure: PEEP Titration guided by Static Compliance; PEEP Titration by Static Compliance: Following the initial recruitment maneuver, an individualized PEEP decremental titration step-protocol is performed to identify the specific PEEP level that maximizes the static compliance of the respiratory system, aiming to optimize the balance between alveolar recruitment and overdistension. Initial Lung Recruitment Maneuver : Prior to individualized PEEP titration, all participants in this arm will undergo an initial standardized lung recruitment maneuver. This procedure will be executed in Pressure-Controlled Ventilation (PCV) mode, utilizing a driving/control pressure of 15 cmH2O. The recruitment process will begin at a baseline Positive End-Expiratory Pressure (PEEP) of 5 cmH2O, followed by incremental steps of 5 cmH2O every 10 seconds until reaching a maximum PEEP of 25 cmH2O. A peak airway pressure limit of 40 cmH2O will be strictly maintained during the maneuver for a total duration of 1 minute.; Other Names: Initial Lung Recruitment Maneuver
Experimental: Transpulmonary Pressure Titration; Patients receive positive end-expiratory pressure (PEEP) titration guided by transpulmonary pressure estimation via an esophageal balloon catheter after undergoing an identical standardized initial lung recruitment maneuver.	Procedure: PEEP Titration guided by Transpulmonary Pressure; PEEP Titration by Transpulmonary Pressure: Following the initial recruitment maneuver, PEEP is titrated and protocolized via real-time esophageal balloon monitoring to target and maintain a slightly positive expiratory transpulmonary pressure, minimizing cyclic alveolar collapse and overdistension. Initial Lung Recruitment Maneuver: Prior to individualized PEEP titration, all participants in this arm will undergo an initial standardized lung recruitment maneuver. This procedure will be executed in Pressure-Controlled Ventilation (PCV) mode, utilizing a driving/control pressure of 15 cmH2O. The recruitment process will begin at a baseline Positive End-Expiratory Pressure (PEEP) of 5 cmH2O, followed by incremental steps of 5 cmH2O every 10 seconds until reaching a maximum PEEP of 25 cmH2O. A peak airway pressure limit of 40 cmH2O will be strictly maintained during the maneuver for a total duration of 1 minute.; Other Names: Initial Lung Recruitment Maneuver

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Early Oxygenation (PaO2/FiO2 Ratio).	The change in gas exchange efficiency is calculated as the absolute difference between the baseline PaO2/FiO2 ratio and the PaO2/FiO2 ratio measured 24 hours after individualized PEEP titration.	Baseline and 24 hours post-PEEP titration

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Evolution of Static Compliance of the Respiratory System	Changes in static compliance calculated via the formula: Tidal Volume / (Plateau Pressure - PEEP).	Baseline, 1, 24, 48, and 72 hours
Evolution of Driving Pressure and Plateau Pressure	Serial monitoring of driving pressure (Plateau Pressure - PEEP) and plateau pressure to evaluate lung stress.	Baseline, 1, 24, 48, and 72 hours
Ventilatory Efficiency	Evaluated using the Ventilatory Ratio (VR), which correlates physiological dead space and minute ventilation.	Baseline, 24, 48, and 72 hours
Incidence of Elevated Airway Opening Pressure (AOP)	Proportion of patients exhibiting an airway opening pressure greater than 5 cmH2O.	Pre-randomization (Baseline)
Ventilator-Free Days (VFD)	Number of days alive and free from invasive mechanical ventilation within a 28-day window.	Up to Day 28
Incidence of Procedure-Related Adverse Events	Proportion of participants experiencing complications due to recruitment maneuvers or PEEP titration (e.g., severe hypotension, barotrauma).	Throughout mechanical ventilation (Up to 28 days)

Collaborators and Investigators

• Sponsor: Hospital Dr. Franco Ravera Zunino
• Investigators: Study Chair: Francisco Cerda, RT., Hospital Dr. Franco Ravera Zunino; Study Chair: Javier Astudillo, MD., Hospital Dr. Franco Ravera Zunino; Study Chair: Jennifer Ayuso, RT., Hospital Dr. Franco Ravera Zunino; Study Chair: Rodrigo Arevalo, RT., Hospital Dr. Franco Ravera Zunino; Study Chair: Carlos Pellegrini, MD., Hospital Dr. Franco Ravera Zunino; Principal Investigator: Esteban Santis, RT., Hospital Dr. Franco Ravera Zunino

Study record dates

Study Major Dates

• Study Start (Estimated): June 1, 2026
• Primary Completion (Estimated): June 30, 2027
• Study Completion (Estimated): September 30, 2027

Study Registration Dates

• First Submitted: May 18, 2026
• First Submitted That Met QC Criteria: May 18, 2026
• First Posted (Actual): May 22, 2026

Study Record Updates

• Last Update Posted (Actual): May 22, 2026
• Last Update Submitted That Met QC Criteria: May 18, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: Ventilator-Induced Lung Injury; Acute Respiratory Distress Syndrome; Respiratory Mechanics; Positive End-Expiratory Pressure; Lung Volume Measurements; Artificial Respiration; Esophageal Monitoring
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Lung Diseases; Respiration Disorders; Lung Injury; Respiratory Distress Syndrome; Ventilator-Induced Lung Injury; Acute Lung Injury
• Other Study ID Numbers: HFRZ-UPC-2026-01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED
• IPD Plan Description: It is not yet known if there will be a plan to make IPD available

Drug and device information, study documents

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