PEEP-induced Effects on Respiratory dRivE and EFfort

NCT07203781 | Recruiting DMC

• 1 other identifier: NL-009995
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

Rationale: In patients with acute hypoxemic respiratory failure (AHRF), preserving spontaneous breathing during mechanical ventilation offers physiological benefits, but also carries risks. While spontaneous breathing improves gas exchange and limits diaphragm atrophy, strong inspiratory efforts may worsen lung and diaphragm injury. Balancing these factors requires refined and tailored strategies, such as the modulation of PEEP. However, the impact of PEEP on neural respiratory drive and inspiratory effort is very heterogenous, and these two entities have only been studied separately in limited subsets of patients and healthy subjects. Additionally, it remains unclear whether the major determinant of PEEP-induced changes in respiratory drive and effort is represented by variations in diaphragm geometry, lung compliance, or by the presence of expiratory muscles recruitment, which may counteract its effect. Objective: The primary objective is to determine the effect of PEEP on diaphragm neuromechanical efficiency (i.e. an index of neural respiratory drive and inspiratory effort) in patients with acute hypoxemic respiratory failure during invasive assisted mechanical ventilation. The secondary objective is to determine the major physiological contributors to PEEP-mediated changes in diaphragm neuromechanical efficiency. Study design: Prospective, physiological study. Study population: Invasively mechanically ventilated adult patients admitted to the ICU. Intervention: For each patient, six different PEEP levels (15-12-10-8-5-2 cmH2O) will be tested during a decremental PEEP trial. During each step, neural respiratory drive, inspiratory effort, expiratory muscle activity, lung inflation pattern through electrical impedance tomography, respiratory muscle geometry and function through ultrasound and surface EMG, gas exchange and hemodynamics data will be collected. Main study parameters/endpoints: The primary outcome of the study will be the evaluation of PEEP-mediated changes in diaphragm neuromechanical efficiency (NME).

Conditions

ARDS (Moderate or Severe); Acute Hypoxemic Respiratory Failure

Keywords

PEEP; effort; drive; PSV; pressure support ventilation; AHRF; ARDS; diaphragm; NME

Outcome Measures

Primary Outcomes (1)

• PEEP-related changes in diaphragm neuromechanical efficiency (NME)

  The primary endpoint of this study will be the evaluation of PEEP-induced changes in diaphragm neuromechanical efficiency (NME, cmH2O/µV), calculated as the ratio between the change in transdiaphragmatic pressure (representing inspiratory effort in cmH2O and assessed through the use of esophageal and gastric manometry) and the change in diaphragm electrical activity (neural respiratory drive, expressed in µV and measured through diaphragm EMG by a dedicated nasogastric tube) for each inspiration (ΔPdi/ΔEAdi). NME is an index of diaphragm efficiency and of potential electromechanical uncoupling, a key PEEP-mediated effect on the diaphragm. Its assessment combines changes in neural respiratory drive and inspiratory effort after a change in PEEP, which will be assessed individually and combined as a ratio as primary outcome.

  Measurements will be conducted throughout the protocol at each of the 6 PEEP levels tested: 15, 12, 10, 8, 5 and 2 cmH2O. Each PEEP step will last 30 minutes, and measurements will be collected recording the last 10 minutes of each step.

Secondary Outcomes (13)

• PEEP-induced changes in inspiratory effort

  Measurements will be conducted throughout the protocol at each of the 6 PEEP levels tested: 15, 12, 10, 8, 5 and 2 cmH2O. Each PEEP step will last 30 minutes, and measurements will be collected recording the last 10 minutes of each step.

• PEEP-induced changes in neural respiratory drive

  Measurements will be conducted throughout the protocol at each of the 6 PEEP levels tested: 15, 12, 10, 8, 5 and 2 cmH2O. Each PEEP step will last 30 minutes, and measurements will be collected recording the last 10 minutes of each step.

• PEEP-induced effects on partitioned respiratory system mechanics

  Measurements will be conducted throughout the protocol at each of the 6 PEEP levels tested: 15, 12, 10, 8, 5 and 2 cmH2O. Each PEEP step will last 30 minutes, and measurements will be collected recording the last 10 minutes of each step.

• PEEP induced effects on tidal volume

  Measurements will be conducted throughout the protocol at each of the 6 PEEP levels tested: 15, 12, 10, 8, 5 and 2 cmH2O. Each PEEP step will last 30 minutes, and measurements will be collected recording the last 10 minutes of each step.

• PEEP-induced effects on end-expiratory lung impedance

  Measurements will be conducted throughout the protocol at each of the 6 PEEP levels tested: 15, 12, 10, 8, 5 and 2 cmH2O. Each PEEP step will last 30 minutes, and measurements will be collected recording the last 10 minutes of each step.

Study Arms (1)

Single arm

EXPERIMENTAL

Other: PEEP level changes

Interventions

PEEP level changes OTHER

For each patient, six different PEEP levels (15-12-10-8-5-2 cmH2O) will be tested during a decremental PEEP trial. During each step, neural respiratory drive, inspiratory effort, expiratory muscle activity, lung inflation pattern through electrical impedance tomography, respiratory muscle geometry and function through ultrasound and surface EMG, gas exchange and hemodynamics data will be collected.

Single arm

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age \> 18 years
• Acute hypoxemic respiratory failure (AHRF) with a PaO2/FiO2-ratio ≤ 200
• Patient on invasive assisted mechanical ventilation in pressure support mode exhibiting valid inspiratory efforts (occlusion pressure \> 5 cmH2O).

You may not qualify if:

• Pre-existent neuromuscular disease
• History of chronic respiratory failure requiring long-term oxygen therapy
• Muscle paralysis
• Pneumothorax
• Contra-indication to EIT monitoring (e.g. burns, pacemaker, thoracic wounds limiting electrode placement)
• Contra-indications for EAdi or oesophageal balloon catheter placement (e.g. history of gastric bypass surgery, gastro-oesophageal junction surgery, oesophageal stricture, recent upper gastrointestinal hemorrhage or known/suspected varices).

Sponsors & Collaborators

• Radboud University Medical Center: lead
• Università Cattolica del Sacro Cuore, Rome, Italy: collaborator

Study Sites (1)

Radboudumc

Nijmegen, Gelderland, 6525 GA, Netherlands

RECRUITING

MeSH Terms

Conditions

Lymphoma, Follicular; Respiratory Insufficiency

Condition Hierarchy (Ancestors)

Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Respiration Disorders; Respiratory Tract Diseases

Study Officials

• Jonne Doorduin, PhD

  Radboud University Medical Center

  PRINCIPAL INVESTIGATOR

• Leo Heunks, M.D., PhD

  Radboud University Medical Center

  STUDY CHAIR

Central Study Contacts

Tommaso Rosà, M.D.

CONTACT

06-50155757; tommaso.rosa@radboudumc.nl

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: OTHER
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Interventional, prospective physiological study

Study Record Dates

• First Submitted: September 4, 2025
• First Posted: October 2, 2025
• Study Start: September 2, 2025
• Primary Completion (Estimated): September 1, 2026
• Study Completion (Estimated): September 1, 2026
• Last Updated: November 17, 2025

Record last verified: 2025-09

Locations

NL (1)