Impact of PEEP on Respiratory Effort During Assisted Ventilation

Official title

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

Overview

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.

Interventions

• 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 respira

Primary outcome measures

• Esophageal pressure swing (ΔPes) [Time frame: During the last 5 minutes of each PEEP level]
• Pressure-time product per minute (PTPmin) [Time frame: During the last 5 minutes of each PEEP level]
• Delta Pocc (ΔPocc) [Time frame: During the last 5 minutes of each PEEP level]
• Muscular Pressure Index (PMI) [Time frame: During the last 5 minutes of each PEEP level]

Secondary outcome measures (7)

• Airway occlusion pressure at 100 ms (P0.1) [Time frame: During the last 5 minutes of each PEEP level]
• Respiratory system compliance (Cest) [Time frame: During the last 5 minutes of each PEEP level]
• Driving pressure [Time frame: During the last 5 minutes of each PEEP level]
• Plateau pressure [Time frame: During the last 5 minutes of each PEEP level]
• Hemodynamic response [Time frame: During the last 5 minutes of each PEEP level]
• Gas exchange (SaFi index) [Time frame: During the last 5 minutes of each PEEP level]
• Dynamic transpulmonary pressure [Time frame: During the last 5 minutes of each PEEP level]

Eligibility criteria

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.

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

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Crossover

Masking

Open label

Primary purpose

Other

Study locations

Chile · 1 center

• Hospital Clinico UC — Santiago

Publications

• 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
• 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
• 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 pressu PMID 27334266
• 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 Cri PMID 32516052
• 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 20 PMID 38295949

Identifiers

NCT: NCT07437846 · 240206001

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗