Influence of Lung Recruitment Potential on PEEP Titration Strategies in ARDS Patients.

N/ANot Yet RecruitingNCT07603310

Hospital Dr. Franco Ravera Zunino52 enrolled

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.

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

PEEP Titration guided by Static CompliancePROCEDURE

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.

PEEP Titration guided by Transpulmonary PressurePROCEDURE

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.

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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).

Outcomes

Primary Outcomes

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.

Time frame: Baseline and 24 hours post-PEEP titration

Secondary Outcomes

Evolution of Static Compliance of the Respiratory System

Changes in static compliance calculated via the formula: Tidal Volume / (Plateau Pressure - PEEP).

Time frame: 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.

Time frame: Baseline, 1, 24, 48, and 72 hours

Ventilatory Efficiency

Evaluated using the Ventilatory Ratio (VR), which correlates physiological dead space and minute ventilation.

Time frame: 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.

Time frame: Pre-randomization (Baseline)

Ventilator-Free Days (VFD)

Number of days alive and free from invasive mechanical ventilation within a 28-day window.

Time frame: 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).

Time frame: Throughout mechanical ventilation (Up to 28 days)