Impact of PEEP Trials on Ventilation-Perfusion Matching in ARDS Patients

Phase 2

• Conditions: ARDS
• Interventions: Drug: 10ml of 10% saline is injected centrally

• Registration Number: NCT06823804
• Lead Sponsor: Ruijin Hospital

Brief Summary

In the treatment of critically ill patients, mechanical ventilation is a key link, and appropriate mechanical ventilation strategies can open the alveoli and improve oxygenation, while inappropriate mechanical ventilation can increase lung injury and seriously affect the prognosis. Ventilator-related lung injury is mainly concentrated in barotrauma, volumetric injury, shear injury, and biological injury, and the monitoring of respiratory ventilation to the level of local ventilation can help to better assess the state of alveolar opening and alveolar collapse, and help to understand the uniformity of gas distribution in the lungs, which is closely related to lung injury. However, how to achieve simple, bedside and real-time lung ventilation and lung volume assessment in clinical work has always been a difficult problem to be overcome. This study intends to explore the changes of local ventilation and blood flow in the lungs during PEEP trail in patients with ARDS monitored by EIT.

Detailed Description

1. Background and Rationale ARDS is associated with heterogeneous lung collapse. The recruitment-to inflation (R/I) ratio has emerged as an index of recruitability, but is usually assessed globally. Electrical impedance tomography (EIT) enables regional assessment of ventilation and may provide more precise determinations of recruitable lung regions, particularly dorsal areas.

2. Objectives Primary objective: To compare the predictive value of regional (dorsal and ventral) versus global R/I for recruitment success in moderate-severe ARDS. Secondary objectives: To classify recruitment phenotypes and evaluate associations with oxygenation, compliance improvement, ventilator-free days, ICU length of stay, and 28-day mortality.

3. Study Design Prospective, single-centre observational cohort study in ICU patients with moderate-severe ARDS. All eligible patients undergo standardised recruitment maneuver and EIT monitoring.

4. Study Setting Ruijin Hospital, Shanghai Jiao Tong University School of Medicine ICU, December 2022 - December 2024.

5. Eligibility Criteria

Inclusion:

Age ≥18 years ARDS diagnosed per Berlin criteria PaO₂/FiO₂ ≤150 mmHg

Exclusion:

Pneumothorax, pneumomediastinum Hemodynamic instability (rising vasopressor need in \<6h) Contraindications to RM or EIT

6. Intervention Standardized PEEP step maneuver from 5 → 15 cmH₂O, maintained for 3 minutes. Continuous EIT monitoring of regional compliance, oxygenation, hemodynamics. Dynamic strain cutoff (\>0.6) or adverse events terminate the maneuver. Ventilation mode: volume control, tidal volume 4-6 mL/kg predicted body weight, plateau ≤28-30 cmH₂O, FiO₂ titrated for SpO₂ 88-92%.

7. Measurements EIT-derived ΔEELI in dorsal and ventral regions Regional and global compliance (Crec and Crs) R/I calculated: Crec/Crs at baseline PEEP Airway opening pressure by low-flow inflation method Primary outcome: recruitment success (≥10% compliance improvement + ≥20 mmHg PaO₂/FiO₂ increase) Secondary: ventilator-free days, ICU LOS, 28-day mortality, dynamic strain

8. Sample Size Calculation Based on pilot data (Δ=0.30, σ=0.40, α=0.05, β=0.20), 36 per group estimated. Adjusted for dropout to target 120 patients.

9. Statistical Analysis Plan Distribution check by Shapiro-Wilk. Paired tests for within-patient comparisons. ROC curves and Youden index for cut-off selection. Multivariate regression for mortality risk factors. Bonferroni correction for multiple comparisons.

10. Safety Monitoring Terminate RM if: MAP \<65 mmHg, SpO₂ \<88%, arrhythmia onset, dynamic strain \>0.6.

Study Timeline

• Study Start: 2022-12-01
• Status Verified: 2024-12
• Study First Submitted: 2024-12-25
• Study First Submitted QC: 2025-02-08
• Study First Posted: 2025-02-12
• Last Update Submitted: 2025-11-13
• Last Update Posted: 2025-11-17
• Primary Completion: 2025-12-01
• Study Completion: 2025-12-01

Recruitment & Eligibility

• Status: ENROLLING_BY_INVITATION
• Sex: All
• Target Recruitment: 120

Inclusion Criteria

• Patients who meet the Berlin definition of ARDS and have been treated with mechanical ventilation (clinical diagnosis of ARDS by the attending ICU physician)
• PaO₂/FiO₂ ≤150 mmHg

Exclusion Criteria

• Age< 18 or >90 years
• Pneumothorax, pneumomediastinum
• Hemodynamic instability (rising vasopressor need in <6h)
• Contraindications to RM or EIT

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
evaluate the feasibility of using EIT to calculate regional recruitment-to-inflation (R/I) ratios	10ml of 10% saline is injected centrally	Regional R/I ratios were computed for the global lung, dorsal (dependent), and ventral (non-dependent) regions of interest (ROIs), which were defined as 50% of the ventro-dorsal lung diameter based on EIT imaging.compare the predictive value of regional (dorsal and ventral) versus global R/I for recruitment success in moderate-severe ARDS.

Primary Outcome Measures

Name	Time	Method
28-day mortality	From enrollment to the end of treatment at 28 days	Statistical analysis of 28-day mortality
recruitment success percent	after recruitment 30min	recruitment( ≥10% compliance improvement ) and Re-check the blood gas ≥20 mmHg PaO₂/FiO₂ increase mean success
Correlation between EIT-derived parameters and clinical outcomes	From enrollment to the end of treatment at 28-day	Correlation analysis between EIT-derived parameters \[e.g., GI index (100%), ROI (100%), V/Q ratio, percentage of dead space (100%)\] and clinical outcomes\[e.g., 28-day mortality\]
Change in Sequential Organ Failure Assessment (SOFA) score from baseline to day 7	From enrollment to the end of treatment at 7 days	Change in Sequential Organ Failure Assessment (SOFA) score from baseline to day 7
Duration of mechanical ventilation from enrollment to successful weaning	From enrollment to the end of treatment at 7 days	Duration of mechanical ventilation in days from enrollment to successful weaning
Improvements in lung compliance	From enrollment to the end of treatment at 7 days	Change in lung compliance measured by EIT and Ventilator (C=△V/△P)during PEEP trials from baseline to 30 minutes at each PEEP level (0，5, 10, 15 and 20 cmH2O)
Regional and global compliance (Crec and Crs)	The continuous EIT monitoring period, which lasts approximately 3 minutes	The EIT detection calculates the corresponding results through a continuous monitoring process that lasts approximately 3 minutes.

Secondary Outcome Measures

Name	Time	Method
Changes in regional ventilation-perfusion matching during PEEP trials	From enrollment to the end of treatment at 7 days	Change in ventilation-perfusion ratio measured by EIT during PEEP trials from baseline to 30 minutes at each PEEP level (5 → 15 cmH₂O )
Change in PaO2/FiO2 ratio	From enrollment to the end of treatment at 7 days	Change in PaO2/FiO2 ratio from baseline to day 7 measured by arterial blood gas analysis
Change in dyspnea severity	From enrollment to the end of treatment at 7 days	Change in dyspnea severity from baseline to day 7 measured by Visual Analog Scale (VAS) score (range 0-100)
Length of ICU stay	From enrollment to the end of treatment at 7 days	Length of ICU stay in days
Incidence of adverse events	From enrollment to the end of treatment at 7 days	Incidence of adverse events as assessed by Common Terminology Criteria for Adverse Events (CTCAE) v4.0

Trial Locations

Locations (1)

Department of Critical Care Medicine，Ruijin Hospital，Shanghai Jiao Tong University School of Medicine，Shanghai，China.; 🇨🇳 Shanghai, Shanghai Municipality, China