Impact of PEEP on Respiratory Effort During Assisted Ventilation (PEEP-EFFORT)

Impact of Positive End-Expiratory Pressure on the Modulation of Respiratory Effort During Assisted Ventilation: A Physiological Randomized Crossover Study

Assisted mechanical ventilation is widely used to preserve diaphragmatic activity and improve lung aeration in patients with acute respiratory failure. However, during assisted ventilation, excessive inspiratory effort may develop and contribute to lung injury, diaphragmatic overload, and patient self-inflicted lung injury.

Optimizing ventilator settings to modulate respiratory effort therefore represents a major physiological and clinical challenge.

Positive end-expiratory pressure (PEEP) is a key determinant of lung recruitment and respiratory system mechanics and may influence inspiratory effort by modifying lung volume, compliance, and respiratory drive. Despite its widespread use, PEEP titration in clinical practice is still mainly guided by oxygenation parameters, while its direct effects on inspiratory effort during assisted mechanical ventilation remain insufficiently characterized.

This physiological randomized crossover study aims to evaluate the effect of four predefined levels of positive end-expiratory pressure (0, 5, 10, and 15 cmH₂O) on the respiratory system and inspiratory effort in adult patients receiving assisted mechanical ventilation. Patients will be exposed to each PEEP level in randomized order, with stabilization and washout periods between conditions, while ventilatory support settings other than PEEP are kept constant.

Study Overview

• Status: Recruiting
• Conditions: Respiratory Failure; Mechanical Ventilation; Effort
• Intervention / Treatment: Other: PEEP Level Adjustment

• Study Type: Interventional
• Enrollment (Estimated): 12
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Diego Lopez Arnello, Physioterapy; Phone Number: +56973805897; Email: diegon.lopez@uc.cl
• Study Contact Backup: Name: Felipe Damiani, PhD, Msc, Physioterapy; Phone Number: +56 9 6669 8823

Study Locations

• Chile
  • Santiago Metropolitan
    • Santiago, Santiago Metropolitan, Chile
      • Recruiting
      • Hospital Clinico UC
      • Contact: Diego Lopez Arnello, Physioterapy; Phone Number: 973805897; Email: diegon.lopez@uc.cl
      • Contact: Roque Basoalto, PhD, Msc, Physioterapy; Phone Number: +56 9 8446 3575; Email: roque.basoalto@gmail.com
      • Principal Investigator: Diego Lopez Arnello, Physioterapy
      • Principal Investigator: Roque Basoalto, PhD, Msc, Physioterapy
      • Principal Investigator: Felipe Damiani, PhD, Msc, Physioterapy

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion criteria:

• Age ≥18 years.
• ICU patients receiving invasive mechanical ventilation (endotracheal tube or tracheostomy).
• Ventilated in an assisted mode with spontaneous breathing
• Clinically stable to undergo protocolized PEEP changes.
• Sedation level compatible with spontaneous breathing and ventilator triggering
• Informed consent from the patient or legally authorized representative.

Exclusion Criteria:

• Contraindication to esophageal balloon placement (if applicable).
• Significant hemodynamic instability or unstable vasopressor requirements.
• Unstable arrhythmia or active myocardial ischemia.
• Undrained pneumothorax or major air leak.
• Controlled ventilation without effective spontaneous effort (apnea, neuromuscular blockade, deep sedation).
• Pregnancy
• Acute or chronic neurological conditions that may impair respiratory drive or interfere with the regulation of spontaneous breathing.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: PEEP 0 cmH₂O; Participants are ventilated with a positive end-expiratory pressure of 0 cmH₂O during assisted mechanical ventilation. Physiological measurements of respiratory effort are obtained during a predefined stabilization period according to the study protocol.	Other: PEEP Level Adjustment; Positive end-expiratory pressure (PEEP) will be adjusted to four predefined levels (0, 5, 10, and 15 cmH₂O) following a randomized crossover protocol during assisted mechanical ventilation. Only the PEEP level will be modified, while all other ventilator settings will be kept constant. Each PEEP level will be maintained for 15 minutes, followed by a 15-minute washout period between levels. Physiological measurements will be obtained during the last 5 minutes of each PEEP level, including respiratory effort assessed using invasive and non-invasive methods, respiratory mechanics, and hemodynamic parameters.; Other Names: PEEP levels
Experimental: PEEP 5 cmH₂O; Participants are ventilated with a positive end-expiratory pressure of 5 cmH₂O during assisted mechanical ventilation. Physiological measurements of respiratory effort are obtained during a predefined stabilization period according to the study protocol.	Other: PEEP Level Adjustment; Positive end-expiratory pressure (PEEP) will be adjusted to four predefined levels (0, 5, 10, and 15 cmH₂O) following a randomized crossover protocol during assisted mechanical ventilation. Only the PEEP level will be modified, while all other ventilator settings will be kept constant. Each PEEP level will be maintained for 15 minutes, followed by a 15-minute washout period between levels. Physiological measurements will be obtained during the last 5 minutes of each PEEP level, including respiratory effort assessed using invasive and non-invasive methods, respiratory mechanics, and hemodynamic parameters.; Other Names: PEEP levels
Experimental: PEEP 10 cmH₂O; Participants are ventilated with a positive end-expiratory pressure of 10 cmH₂O during assisted mechanical ventilation. Physiological measurements of respiratory effort are obtained during a predefined stabilization period according to the study protocol.	Other: PEEP Level Adjustment; Positive end-expiratory pressure (PEEP) will be adjusted to four predefined levels (0, 5, 10, and 15 cmH₂O) following a randomized crossover protocol during assisted mechanical ventilation. Only the PEEP level will be modified, while all other ventilator settings will be kept constant. Each PEEP level will be maintained for 15 minutes, followed by a 15-minute washout period between levels. Physiological measurements will be obtained during the last 5 minutes of each PEEP level, including respiratory effort assessed using invasive and non-invasive methods, respiratory mechanics, and hemodynamic parameters.; Other Names: PEEP levels
Experimental: PEEP 15 cmH₂O; Participants are ventilated with a positive end-expiratory pressure of 15 cmH₂O during assisted mechanical ventilation. Physiological measurements of respiratory effort are obtained during a predefined stabilization period according to the study protocol.	Other: PEEP Level Adjustment; Positive end-expiratory pressure (PEEP) will be adjusted to four predefined levels (0, 5, 10, and 15 cmH₂O) following a randomized crossover protocol during assisted mechanical ventilation. Only the PEEP level will be modified, while all other ventilator settings will be kept constant. Each PEEP level will be maintained for 15 minutes, followed by a 15-minute washout period between levels. Physiological measurements will be obtained during the last 5 minutes of each PEEP level, including respiratory effort assessed using invasive and non-invasive methods, respiratory mechanics, and hemodynamic parameters.; Other Names: PEEP levels

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Esophageal pressure swing (ΔPes)	Esophageal pressure swing (ΔPes), defined as the absolute difference between end-expiratory and end-inspiratory esophageal pressure, measured using an esophageal balloon catheter.	During the last 5 minutes of each PEEP level
Pressure-time product per minute (PTPmin)	Pressure-time product per minute (PTPmin), expressed as cmH₂O·s/min, measured using an esophageal balloon catheter as an index of global inspiratory effort.	During the last 5 minutes of each PEEP level
Delta Pocc (ΔPocc)	Airway occlusion pressure-derived index (ΔPocc) obtained from brief ventilator-based airway occlusion maneuvers as a non-invasive measurement of inspiratory effort.	During the last 5 minutes of each PEEP level
Muscular Pressure Index (PMI)	Muscular Pressure Index (PMI) calculated from ventilator-based airway occlusion maneuvers as a non-invasive estimate of inspiratory muscle pressure.	During the last 5 minutes of each PEEP level

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Airway occlusion pressure at 100 ms (P0.1)	Airway occlusion pressure at 100 milliseconds (P0.1), measured by the mechanical ventilator as an index of respiratory drive.	During the last 5 minutes of each PEEP level
Respiratory system compliance (Cest)	Static compliance of the respiratory system (Cest) measured during assisted mechanical ventilation at each PEEP level.	During the last 5 minutes of each PEEP level
Driving pressure	Driving pressure calculated as the difference between airway plateau pressure and total PEEP during assisted mechanical ventilation at each PEEP level.	During the last 5 minutes of each PEEP level
Plateau pressure	Airway plateau pressure measured during assisted mechanical ventilation at each PEEP level.	During the last 5 minutes of each PEEP level
Hemodynamic response	Hemodynamic response assessed using heart rate, arterial blood pressure, respiratory rate and oxygen saturation during assisted mechanical ventilation at different PEEP levels.	During the last 5 minutes of each PEEP level
Gas exchange (SaFi index)	Gas exchange assessed using the SaFi index (SpO₂/FiO₂ ratio) at each PEEP level.	During the last 5 minutes of each PEEP level
Dynamic transpulmonary pressure	ynamic transpulmonary pressure calculated during assisted mechanical ventilation using airway pressure and esophageal pressure measurements obtained with an esophageal balloon catheter.	During the last 5 minutes of each PEEP level

Collaborators and Investigators

• Sponsor: Pontificia Universidad Catolica de Chile
• Collaborators: Clínica Universidad de los Andes
• Investigators: Principal Investigator: Roque Basoalto, PhD, Msc, Physioterapy, Pontifica Universidad Catolica de Chile; Study Chair: Sebastian Morales, Physician, Pontifica Universidad Catolica de Chile; Principal Investigator: Alejandro Bruh Bruhn, Pontifica Universidad Catolica de Chile

Publications and helpful links

General Publications

• Mauri T, Yoshida T, Bellani G, Goligher EC, Carteaux G, Rittayamai N, Mojoli F, Chiumello D, Piquilloud L, Grasso S, Jubran A, Laghi F, Magder S, Pesenti A, Loring S, Gattinoni L, Talmor D, Blanch L, Amato M, Chen L, Brochard L, Mancebo J; PLeUral pressure working Group (PLUG-Acute Respiratory Failure section of the European Society of Intensive Care Medicine). Esophageal and transpulmonary pressure in the clinical setting: meaning, usefulness and perspectives. Intensive Care Med. 2016 Sep;42(9):1360-73. doi: 10.1007/s00134-016-4400-x. Epub 2016 Jun 22.
• Foti G, Cereda M, Banfi G, Pelosi P, Fumagalli R, Pesenti A. End-inspiratory airway occlusion: a method to assess the pressure developed by inspiratory muscles in patients with acute lung injury undergoing pressure support. Am J Respir Crit Care Med. 1997 Oct;156(4 Pt 1):1210-6. doi: 10.1164/ajrccm.156.4.96-02031.
• Goligher EC, Dres M, Patel BK, Sahetya SK, Beitler JR, Telias I, Yoshida T, Vaporidi K, Grieco DL, Schepens T, Grasselli G, Spadaro S, Dianti J, Amato M, Bellani G, Demoule A, Fan E, Ferguson ND, Georgopoulos D, Guerin C, Khemani RG, Laghi F, Mercat A, Mojoli F, Ottenheijm CAC, Jaber S, Heunks L, Mancebo J, Mauri T, Pesenti A, Brochard L. Lung- and Diaphragm-Protective Ventilation. Am J Respir Crit Care Med. 2020 Oct 1;202(7):950-961. doi: 10.1164/rccm.202003-0655CP.
• Morais CCA,Koyama Y,Yoshida T,Plens GM,Gomes S,Lima CAS,Ramos OPS,Pereira SM,Kawaguchi N,Yamamoto H,Uchiyama A,Borges JB,Vidal Melo MF,Tucci MR,Amato MBP,Kavanagh BP,Costa ELV,Fujino Y
• Bello G, Giammatteo V, Bisanti A, Delle Cese L, Rosa T, Menga LS, Montini L, Michi T, Spinazzola G, De Pascale G, Pennisi MA, Ribeiro De Santis Santiago R, Berra L, Antonelli M, Grieco DL. High vs Low PEEP in Patients With ARDS Exhibiting Intense Inspiratory Effort During Assisted Ventilation: A Randomized Crossover Trial. Chest. 2024 Jun;165(6):1392-1405. doi: 10.1016/j.chest.2024.01.040. Epub 2024 Jan 29.

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2025
• Primary Completion (Estimated): April 1, 2026
• Study Completion (Estimated): July 1, 2026

Study Registration Dates

• First Submitted: February 23, 2026
• First Submitted That Met QC Criteria: February 23, 2026
• First Posted (Actual): February 27, 2026

Study Record Updates

• Last Update Posted (Actual): February 27, 2026
• Last Update Submitted That Met QC Criteria: February 23, 2026
• Last Verified: January 1, 2026

More Information

Terms related to this study

• Keywords: Breathing effort; Assisted mechanical ventilation; Inspiratory Effort
• Additional Relevant MeSH Terms: Pathologic Processes; Respiratory Tract Diseases; Respiration Disorders; Pathological Conditions, Signs and Symptoms; Respiratory Insufficiency; Respiratory Aspiration
• Other Study ID Numbers: 240206001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No