COMPARISON OF LUNG RECRUITABILITY ASSESSMENT BY HYSTERESIS RATIO AND RECRUITMENT-TO-INFLATION RATIO, AND PEEP TITRATION IN ARDS.

Official title

COMPARISON OF LUNG RECRUITABILITY ASSESSMENT BY HYSTERESIS RATIO AND RECRUITMENT-TO-INFLATION RATIO AND THE USE OF DIFFERENT PEEP TITRATION METHODS IN PATIENTS WITH ACUTE RESPIRATORY DISTRESS SYNDROME (ARDS)

Overview

This multicenter, single-blind physiological study aims to compare two bedside methods for assessing lung recruitability in mechanically ventilated patients with acute respiratory distress syndrome (ARDS): the recruitment-to-inflation (R/I) ratio and the pressure-volume (PV) loop hysteresis ratio. Lung recruitability will be defined according to the reduction in lung collapse measured by electrical impedance tomography (EIT) during a standardized lung recruitment maneuver. Following baseline measurements, participants will undergo sequential physiological assessments, including lung recruitability evaluation using both the R/I ratio and a low-flow PV loop, a standardized lung recruitment maneuver with a decremental PEEP trial, and a second PV loop performed at a lower maximum inflation pressure. The order of the R/I ratio assessment and the PV loop maneuver will be randomized. In a final crossover phase, four different PEEP titration strategies will be evaluated in randomized order. Each strategy will be applied for 15 minutes and separated by a washout period at the patient's baseline clinical PEEP. Respiratory mechanics, gas exchange, ventilation/perfusion distribution, and hemodynamic variables will be assessed throughout the protocol. The primary objective is to determine the agreement between the hysteresis ratio and the R/I ratio for identifying lung recruitability. Secondary objectives include evaluating whether a PV loop performed with a lower maximum pressure provides similar information on recruitability and comparing the physiological effects of different PEEP titration strategies. Approximately 30 patients with moderate-to-severe ARDS receiving invasive mechanical ventilation will be enrolled.

Detailed description

Acute respiratory distress syndrome (ARDS) is a severe form of respiratory failure that requires mechanical ventilation. One of the main challenges in ventilator management is selecting the optimal level of positive end-expiratory pressure (PEEP), as patients differ in their potential for lung recruitment. Individualizing PEEP may help improve lung protection by reducing lung collapse while avoiding overdistension. The study is designed to improve the understanding of bedside tools for assessing lung recruitability and to evaluate their potential role in personalizing mechanical ventilation in patients with ARDS.

Patients meeting the inclusion criteria will be enrolled in this multicenter, single-blind physiological study after informed consent has been obtained. Continuous monitoring will include electrical impedance tomography (EIT), esophageal pressure, mechanical ventilation parameters, end-tidal carbon dioxide, and standard hemodynamic monitoring throughout the study protocol.

After enrollment, a fluid responsiveness assessment will be performed using a standardized tidal volume challenge to optimize hemodynamic conditions before study interventions. Baseline measurements will then be obtained after 15 minutes at the patient's clinical ventilator settings and will include respiratory mechanics, arterial blood gases, ventilation/perfusion (V/Q) analysis, and hemodynamic variables.

The primary endpoint is the comparison between the hysteresis ratio and the recruitment-to-inflation ratio for the assessment of lung recruitability, using the reduction in lung collapse measured by EIT as the reference standard. Secondary endpoints include comparison of recruitability assessment obtained with PV loops performed at maximum inflation pressures of 40 and 30 cmH₂O, and evaluation of the physiological effects of different PEEP titration methods on respiratory mechanics, ventilation/perfusion matching, gas exchange, and hemodynamics. Clinical outcomes, including duration of mechanical ventilation, ICU and hospital length of stay, and mortality, will also be recorded.

The first study phase evaluates lung recruitability using two bedside methods: the recruitment-to-inflation (R/I) ratio and a low-flow pressure-volume loop with a maximum pressure of 40 cmH₂O (PVloop40). The order of these two assessments will be computer-randomized. During the R/I assessment, measurements will be obtained at PEEP levels of 5 and 15 cmH₂O, followed by a single-breath maneuver to calculate the recruitment-to-inflation ratio. The PVloop40 maneuver will be used to calculate the hysteresis ratio from the inspiratory and expiratory limbs of the pressure-volume curve.

Following recruitability assessment, patients will undergo a standardized lung recruitment maneuver. PEEP will be progressively increased from 5 to 24 cmH₂O with intermediate stabilization periods to assess patient tolerance. After recruitment, respiratory mechanics, arterial blood gases, and hemodynamic measurements will be repeated at the highest PEEP level.

A decremental PEEP trial will subsequently be performed from 24 to 6 cmH₂O using 2 cmH₂O decrements maintained for at least 3 minutes each. Electrical impedance tomography data obtained during this maneuver will be used to quantify regional lung collapse and overdistension and to identify the optimal PEEP according to EIT-derived criteria. After completion of the decremental trial, a second low-flow pressure-volume loop with a maximum pressure of 30 cmH₂O (PVloop30) will be performed to determine whether recruitability can be accurately assessed using lower inflation pressures.

In the final phase, participants will undergo a randomized crossover comparison of four PEEP titration strategies: (1) transpulmonary pressure-guided PEEP, (2) EIT-guided PEEP, (3) R/I ratio-guided PEEP, and (4) compliance-guided PEEP. The order of the four strategies will be computer-generated. Each PEEP strategy will be maintained for 15 minutes, followed by assessment of respiratory mechanics, ventilation/perfusion matching, and hemodynamic variables. Between interventions, patients will return to their baseline clinical PEEP for a 15-minute washout period before initiation of the next strategy.

Interventions

• Procedure Physiological lung recruitability assessment and PEEP titration protocol
  Participants undergo a standardized physiological protocol including lung recruitability assessment using the recruitment-to-inflation ratio and pressure-volume loop hysteresis ratio, a standardized lung recruitment maneuver, a decremental PEEP trial, and crossover evaluation of four PEEP titration strategies based on transpulmonary pressure, electrical impedance tomography, respiratory system compliance, and the recruitment-to-inflation ratio. The order of the recruitability assessments and PEE

Primary outcome measures

• Agreement between the hysteresis ratio and the recruitment-to-inflation (R/I) ratio for assessing lung recruitability [Time frame: During the study procedure (approximately within 2-3 hours after enrollment).]

Secondary outcome measures (2)

• Agreement between PVloop30 and PVloop40 for the assessment of lung recruitability [Time frame: During the study procedure.]
• Respiratory mechanics and ventilation/perfusion (V/Q) changes according to different PEEP titration methods [Time frame: During the study procedure, after 15 minutes of each randomized PEEP titration strategy]

Eligibility criteria

Inclusion criteria

• Intubated patients with acute respiratory distress syndrome (ARDS): PaO2/FiO2 ratio <200, with bilateral infiltrates of non-cardiogenic origin, with a PEEP of at least 5 cmH2O.
• The patient is receiving mechanical ventilation and continuous sedation.
• The patient has an esophageal balloon.
• Written informed consent signed and dated by the patient or one relative in case the patient is unable to consent, after a full explanation of the study by the investigator and prior to study participation

Exclusion criteria

• Patients with< 18 years old
• Pregnant woman
• Lung recruitment maneuvers are deemed unsafe by the medical team
• Unable to fit EIT belt due to patient size
• Contraindications to EIT monitoring (e.g. burns, pacemaker, thoracic wounds limiting electrode placement)
• Hemodynamic instability (Systolic BP < 75 mmHg or MAP < 60 mmHg despite vasopressors and/or heart rate < 55 bpm)
• Hypernatremia (Na+ >145mEq/L)
• The formalized ethical decision to withhold or withdraw life support
• Patient under guardianship
• Patients deprived of liberties
• Impossibility to give informed consent by both patient and family (i.e. language barrier)
• Patient was already enrolled in the present study in a previous episode of acute respiratory failure.

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

Healthy volunteers: No

Study design

Allocation

N/A

Model

Sequential

Masking

Open label

Primary purpose

Basic science

Study locations

Center list to be confirmed — check the primary protocol.

Publications

• Mauri T, Eronia N, Turrini C, Battistini M, Grasselli G, Rona R, Volta CA, Bellani G, Pesenti A. Bedside assessment of the effects of positive end-expiratory pressure on lung inflation and recruitment by the helium dilution technique and electrical impedance tomography. Intensive Care Med. 2016 Oct;42(10):1576-1587. doi: 10.1007/s00134-016-4467-4. Epub 2016 Aug 12. PMID 27518321
• Scaramuzzo G, Spadaro S, Dalla Corte F, Waldmann AD, Bohm SH, Ragazzi R, Marangoni E, Grasselli G, Pesenti A, Volta CA, Mauri T. Personalized Positive End-Expiratory Pressure in Acute Respiratory Distress Syndrome: Comparison Between Optimal Distribution of Regional Ventilation and Positive Transpulmonary Pressure. Crit Care Med. 2020 Aug;48(8):1148-1156. doi: 10.1097/CCM.0000000000004439. PMID 32697485
• Millington SJ, Cardinal P, Brochard L. Setting and Titrating Positive End-Expiratory Pressure. Chest. 2022 Jun;161(6):1566-1575. doi: 10.1016/j.chest.2022.01.052. Epub 2022 Feb 5. PMID 35131298
• Chiumello D, Arnal JM, Umbrello M, Cammaroto A, Formenti P, Mistraletti G, Bolgiaghi L, Gotti M, Novotni D, Reidt S, Froio S, Coppola S. Hysteresis and Lung Recruitment in Acute Respiratory Distress Syndrome Patients: A CT Scan Study. Crit Care Med. 2020 Oct;48(10):1494-1502. doi: 10.1097/CCM.0000000000004518. PMID 32897667
• Chen L, Del Sorbo L, Grieco DL, Junhasavasdikul D, Rittayamai N, Soliman I, Sklar MC, Rauseo M, Ferguson ND, Fan E, Richard JM, Brochard L. Potential for Lung Recruitment Estimated by the Recruitment-to-Inflation Ratio in Acute Respiratory Distress Syndrome. A Clinical Trial. Am J Respir Crit Care Med. 2020 Jan 15;201(2):178-187. doi: 10.1164/rccm.201902-0334OC. PMID 31577153

Identifiers

NCT: NCT07713420 · PRNA018/25

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗