Impact of PEEP on Respiratory Effort During Assisted Ventilation

NCT07437846 | Recruiting DMC

• 1 other identifier: 240206001
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Mechanical Ventilation; Respiratory Failure; Effort

Keywords

Assisted mechanical ventilation; Inspiratory Effort; Breathing effort

Outcome Measures

Primary Outcomes (4)

• 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 Outcomes (7)

• Airway occlusion pressure at 100 ms (P0.1)

  During the last 5 minutes of each PEEP level

• Respiratory system compliance (Cest)

  During the last 5 minutes of each PEEP level

• Driving pressure

  During the last 5 minutes of each PEEP level

• Plateau pressure

  During the last 5 minutes of each PEEP level

• Hemodynamic response

  During the last 5 minutes of each PEEP level

Study Arms (4)

PEEP 0 cmH₂O

EXPERIMENTAL

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

PEEP 5 cmH₂O

EXPERIMENTAL

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

PEEP 10 cmH₂O

EXPERIMENTAL

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

PEEP 15 cmH₂O

EXPERIMENTAL

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

Interventions

PEEP Level Adjustment OTHER

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.

Also known as: PEEP levels

PEEP 0 cmH₂O; PEEP 10 cmH₂O; PEEP 15 cmH₂O; PEEP 5 cmH₂O

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.
• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Pontificia Universidad Catolica de Chile: lead
• Clínica Universidad de los Andes: collaborator

Study Sites (1)

Hospital Clinico UC

Santiago, Santiago Metropolitan, Chile

RECRUITING

Related Publications (5)

• 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. High Positive End-Expiratory Pressure Renders Spontaneous Effort Noninjurious. Am J Respir Crit Care Med. 2018 May 15;197(10):1285-1296. doi: 10.1164/rccm.201706-1244OC.

  PMID: 29323536 BACKGROUND

• 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.

  PMID: 9351624 BACKGROUND

• 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.

  PMID: 27334266 BACKGROUND

• 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.

  PMID: 32516052 BACKGROUND

• 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.

  PMID: 38295949 BACKGROUND

MeSH Terms

Conditions

Respiratory Insufficiency; Respiratory Aspiration

Condition Hierarchy (Ancestors)

Respiration Disorders; Respiratory Tract Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Roque Basoalto, PhD, Msc, Physioterapy

  Pontifica Universidad Catolica de Chile

  PRINCIPAL INVESTIGATOR

• Sebastian Morales, Physician

  Pontifica Universidad Catolica de Chile

  STUDY CHAIR

• Alejandro Bruh Bruhn

  Pontifica Universidad Catolica de Chile

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Diego Lopez Arnello, Physioterapy

CONTACT

+56973805897; diegon.lopez@uc.cl

Felipe Damiani, PhD, Msc, Physioterapy

CONTACT

+56 9 6669 8823

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: After informed consent is obtained, participants admitted to the ICU of Hospital Clínico UC or Clínica Universidad de los Andes and receiving invasive mechanical ventilation will undergo a randomized physiological crossover intervention. Pressure support will remain unchanged throughout the study and will be maintained at the level programmed by the treating medical team prior to study initiation. Four predefined levels of positive end-expiratory pressure (PEEP: 0, 5, 10, and 15 cmH₂O) will be applied in a randomized sequence, each lasting 15 minutes. Between each PEEP level, a 15-minute washout period will be performed using the same PEEP level set by the treating medical team before the intervention. During the final 5 minutes of each PEEP stage, physiological measurements of respiratory effort will be recorded. If clinical instability occurs, the intervention will be stopped and ventilator settings will be returned to baseline.

Study Record Dates

• First Submitted: February 23, 2026
• First Posted: February 27, 2026
• Study Start: January 1, 2025
• Primary Completion: April 1, 2026
• Study Completion (Estimated): July 1, 2026
• Last Updated: February 27, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share

Locations

CL (1)