Influence of Lung Recruitment Potential on Positive End-Expiratory Pressure (PEEP) Titration Strategies in Acute Respiratory Distress Syndrome (ARDS) Patients.

Official title

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

Overview

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.

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.

Interventions

• Procedure Positive End-Expiratory Pressure (PEEP) Titration guided by Static Compliance
  Positive End-Expiratory Pressure (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 st
• Procedure Positive End-Expiratory Pressure (PEEP) Titration guided by Transpulmonary Pressure
  Positive End-Expiratory 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 maneuv

Primary outcome measures

• Change in Early Oxygenation (PaO2/FiO2 Ratio). [Time frame: Baseline and 24 hours post-PEEP titration]

Secondary outcome measures (6)

• Evolution of Static Compliance of the Respiratory System [Time frame: Baseline, 1, 24, 48, and 72 hours]
• Evolution of Driving Pressure and Plateau Pressure [Time frame: Baseline, 1, 24, 48, and 72 hours]
• Ventilatory Efficiency [Time frame: Baseline, 24, 48, and 72 hours]
• Incidence of Elevated Airway Opening Pressure (AOP) [Time frame: Pre-randomization (Baseline)]
• Ventilator-Free Days (VFD) [Time frame: Up to Day 28]
• Incidence of Procedure-Related Adverse Events [Time frame: Throughout mechanical ventilation (Up to 28 days)]

Eligibility criteria

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 Partial pressure of oxygen in arterial blood/Fraction of inspired oxygen <= 200 mmHg with Positive End-Expiratory Pressure (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).

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

Chile · 1 center

• Dr. Franco Ravera Zunino Hospital — Rancagua

Identifiers

NCT: NCT07603310 · HFRZ-UPC-2026-01

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗