The Impact of Low Versus High Positive End-expiratory Pressure on Diaphragm Function, Ventilation Efficiency, and Lung Mechanics

Not Applicable

Not yet recruiting

• Conditions: Respiratory Failure; ARDS (Acute Respiratory Distress Syndrome); Pneumonia; Respiratory Insufficiency

• Registration Number: NCT07188038
• Lead Sponsor: Vastra Gotaland Region

Brief Summary

The goal of this interventional study is to evaluate the effect of different positive end-expiratory pressures (PEEP) on lung and diaphragm function in patients mechanically ventilated with pressure support ventilation in the intensive care unit. The main questions aim to answer:

Does higher PEEP level affect diaphragm contractions and ventilatory efficiency? Does higher PEEP level limit inspiratory efforts? Does higher PEEP level affect lung compliance?

The participants will be subjected to three different PEEP levels during pressure support ventilation:

Low PEEP (4 cmH2O), Medium PEEP (10 cmH2O), High PEEP (16 cmH2O).

The lung and diaphragm function will be evaluated using high-resolution esophageal manometry, electrical activity of the diaphragm, external diaphragm ultrasound and spirometric ventilator data.

Detailed Description

Not available

Study Timeline

• Status Verified: 2025-09
• Study First Submitted: 2025-09-01
• Study First Submitted QC: 2025-09-15
• Last Update Submitted: 2025-09-15
• Study First Posted: 2025-09-23
• Last Update Posted: 2025-09-23
• Study Start: 2025-10-01
• Primary Completion: 2027-07-31
• Study Completion: 2027-12-31

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 25

Inclusion Criteria

• Mechanical ventilation with pressure support or mechanical ventilation with possibility to transition to pressure support
• Oxygen requirement ≤ 50%
• Pressure support ≤ 12 cmH2O
• PEEP ≤ 12 cmH2O
• Age ≥ 18 years
• Adequate intravascular volume status

Exclusion Criteria

• Circulatory instability
• Brain death diagnosis/brain death evaluation
• Norepinephrine dose > 0.4 µg/kg/min
• Muscle relaxation administered within 2 hours
• Pregnancy
• Contraindication to esophageal catheterization (e.g., esophageal varices)
• Conditions with increased risk of pneumothorax (such as severe COPD (Chronic Obstructive Pulmonary Disease) or extensive emphysema)
• Untreated pneumothorax
• Symptomatic airway obstruction

Discontinuation criteria during ongoing study intervention:

• Heart rate > 120 beats/min
• Systolic blood pressure > 180 mmHg
• Inspired oxygen fraction > 70%
• Respiratory rate > 35/min
• RASS (Richmond Agitation Sedation Scale) ≥ 2
• Doubling of norepinephrine dose or increase of norepinephrine dose to > 0.5 µg/kg/min to maintain mean arterial pressure
• Bradycardia < 45 beats/min

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Primary Outcome Measures

Name	Time	Method
Inspiratory effort	Measured during 5 uninterrupted breaths 10 minutes after application of interventional PEEP level	Inspiratory effort will be measured by the tidal change in esophageal pressure (in cmH2O) during assisted breathing. The esophageal pressure will be measured using a high-resolution manometry catheter. The change from expiratory to inspiratory esophageal pressure will represent the tidal change and be used to estimate the inspiratory effort.
Inspiratory drive	Measured during 5 uninterrupted breaths 10 minutes after application of interventional PEEP level	The electric activity of the diaphragm (Eadi) will be measured using a NAVA (neurally adjusted ventilatory assist) catheter. The change from end-expiratory to inspiratory Eadi will be calculated. This represents the inspiratory drive. The Eadi will be measured in Voltage.
Effort-to-drive ratio	Calculated from the measures collected 10 minutes after application of interventional PEEP level	The effort-to-drive ratio (EDR) will be calculated as the inspiratory effort (tidal change in esophageal pressure) divided by the inspiratory drive (tidal change in electric activity of the diaphragm).
Neuromechanical efficiency	Calculated from the measures collected during the occlusion manoeuvre performed 10-15 minutes after application of interventional PEEP level	The neuromechanical efficiency will be calculated as the change in airway pressure during an occlusion test (Pocc) (measured from end-expiration to maximum negative pressure during the occlusion manoeuvre) divided by the inspiratory change in electric activity of the diaphragm (from end-expiration to inspiration).
Thickening fraction of the diaphragm (TFdi)	Measured 10 minutes after application of interventional PEEP level	Measured by ultrasound at the right hemidiaphragm. The thickening fraction of the diaphragm (TFdi) will be calculated as \[ (end-inspiratory diaphragm thickness - end-expiratory diaphragm thickness) / end-expiratory diaphragm thickness) \].
Transpulmonary driving pressure	Measured during 5 breaths 10 minutes after application of interventional PEEP level	Change in transpulmonary pressure ( airway pressure - esophageal pressure) from end-expiration to end-inspiration will be calculated using ventilator data and high-resolution manometry
Occlusion pressure	The occlusion pressure will be measured during an occlusion manoeuvre performed 10-15 minutes after application of interventional PEEP level.	The airway pressure drop from end-expiration to minimum pressure during an occlusion manoeuvre will be measured using the ventilator. The pressure drop indicates the inspiratory effort. It will be measured in cmH2O.

Secondary Outcome Measures

Name	Time	Method
Airway driving pressure	Measured during an inspiratory hold performed 10-15 minutes after application of interventional PEEP level	Difference in airway pressure between end-expiration and during an inspiratory hold will be calculated from the ventilator data.
Lung compliance	Measured during an inspiratory hold performed 10 - 15 minutes after application of interventional PEEP level	Lung compliance will be calculated as the tidal volume divided by the change in transpulmonary pressure from end-expiration to end-inspiration.
Thickening fraction of the expiratory abdominal muscles (TFabd)	Measured 10 minutes after application of interventional PEEP level	The abdominal muscles will be visualized by ultrasound in the anterior axillary line, midway between the inferior border of the ribcage and the iliac crest. The thickening fraction will be calculated as \[(expiratory thickness - end-inspiratory thickness) / end-inspiratory thickness \].
Oxygenation	The blood gas will be collected 10 minutes after application of interventional PEEP level	The PFI (PaO2/FiO2 ratio) will be calculated as arterial PaO2 (partial pressure of oxygen) divided by the FiO2 (fraction of inspired oxygen)
Respiratory system compliance	Measured during an inspiratory hold manoeuvre performed 10-15 minutes after the application of interventional PEEP level.	The respiratory system compliance will be calculated as the tidal volume divided by the airway driving pressure during an inspiratory hold.

Trial Locations

Locations (2)

Central intensivvårdsavdelning, Sahlgrenska University Hospital; 🇸🇪 Gothenburg, Västra Götaland County, Sweden

Thorax intensivvårdsavdelning, Område 6, Sahlgrenska University Hospital, Västra Götalandsregionen; 🇸🇪 Gothenburg, Västra Götaland County, Sweden