Skip to main content
OpenTrials
Not Yet Recruiting

NCT Number: NCT07188038

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

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.

Not Yet Recruiting

Trial opening soon.

Get Notified

Key information

Conditions

Respiratory Failure ARDS (Acute Respiratory Distress Syndrome) Acute Lung Injury Infections Lung Diseases Lung Injury Pneumonia Respiration Disorders Respiratory Insufficiency Respiratory Tract Diseases Respiratory Tract Infections

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

Central intensivvårdsavdelning, Sahlgrenska University Hospital, Gothenburg, Västra Götaland County, Sweden

Loading trial locations.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

Low positive end-expiratory pressure

Procedure

Low (4 cmH2O) positive end-expiratory pressure (PEEP) will be applied during pressure support ventilation. The PEEP level will be kept for 10 minutes prior to data acquisition.

Medium positive end-expiratory pressure

Procedure

Medium (10 cmH2O) positive end-expiratory pressure (PEEP) will be applied during pressure support ventilation. The PEEP level will be kept for 10 minutes prior to data acquisition.

High positive end-expiratory pressure

Procedure

High(16 cmH2O) positive end-expiratory pressure (PEEP) will be applied during pressure support ventilation. The PEEP level will be kept for 10 minutes prior to data acquisition.

Primary outcomes

  1. Inspiratory effort

    Time frame: 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.

  2. Inspiratory drive

    Time frame: 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.

  3. Effort-to-drive ratio

    Time frame: 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).

  4. Neuromechanical efficiency

    Time frame: 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).

  5. Thickening fraction of the diaphragm (TFdi)

    Time frame: 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) ].

  6. Transpulmonary driving pressure

    Time frame: 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

  7. Occlusion pressure

    Time frame: 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 outcomes

  1. Airway driving pressure

    Time frame: 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.

  2. Lung compliance

    Time frame: 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.

  3. Thickening fraction of the expiratory abdominal muscles (TFabd)

    Time frame: 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 ].

  4. Oxygenation

    Time frame: 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)

  5. Respiratory system compliance

    Time frame: 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.

Other outcomes

  1. Central venous oxygen saturation (ScvO2)

    Time frame: Venous blood gas will be collected 10 minutes after application of interventional PEEP level

    Oxygen saturation of venous blood drawn from a central venous catheter.

  2. Tidal volume

    Time frame: Measured in 5 breaths 10 minutes after the application of interventional PEEP level.

    The volume change from end-expiration to end-inspiration. Will be acquired from the ventilator.

  3. Respiratory rate

    Time frame: Measured 10 minutes after the application of interventional PEEP level.

    The number of breaths per minutes (respiratory rate) will be calculated from the volume-time curve acquired from the ventilator.

  4. Dead space

    Time frame: The dead space will be calculated 10 minuted after application of interventional PEEP level.

    Dead space (volume of gas not participating in gas exchange) will be calculated from the difference between arterial and end-expiratory partial pressure of Carbon dioxide, using blood gas analysis and capnography.

  5. Change in end-expiratory lung volume

    Time frame: Measured in the 15 breaths following a PEEP change.

    The change in end-expiratory lung volume will be calculated as the accumulated difference in inspired and expired gas volume during the first 15 breaths after a PEEP change. This will be acquired using the ventilator.

  6. End-expiratory diaphragm thickness

    Time frame: This will be measured during end-expiration 10 minutes after the application of interventional PEEP level.

    The end-expiratory diaphragm thickness will be measured by ultrasound as the thickness of the diaphragm at the right hemisphere at end-expiration.

  7. Neuroventilatory efficiency

    Time frame: Measured from 5 breaths 10 minutes after the application of interventional PEEP level.

    The neuroventilatory efficiency will be calculated as the tidal volume divided by the change from end-expiratory to inspiratory electric activity of the diaphragm (Eadi). The tidal volume will be calculated using data from the ventilator and Eadi acquired using a NAVA (neurally adjusted ventilatory assist) catheter.

  8. Neuromuscular efficiency

    Time frame: This will be calculated from 5 breaths acquired 10 minutes after the application of interventional PEEP level.

    The neuromuscular efficiency will be calculated as the change in transdiaphragmatic pressure (esophageal pressure - gastric pressure) from end-expiration to inspiration divided by the change in electric activity of the diaphragm from end-expiration to inspiration.

  9. Electric activity of the diaphragm

    Time frame: Measured during 5 breaths 10 minutes after application of interventional PEEP level. Additionally measured during an occlusion manoeuvre 10-15 minutes after application of interventional PEEP level.

    Electric activity of the diaphragm (Eadi) during end-expiration, inspiration and occlusion manoeuvres will be measured by NAVA (neurally adjusted ventilator assist) catheters in Voltages

  10. Thickening fraction of the intercostal muscles

    Time frame: Measured 10 minutes after application of interventional PEEP level

    Intercostal muscles will be examined by ultrasound in the cranio-caudal direction at the second intercostal space. The thickening fraction of the intercostal muscles (TFic) will be calculated as the [ (end-inspiratory intercostal thickness - end-expiratory intercostal thickness) / end-expiratory intercostal thickness) ].

Study contacts

Contact information is provided by the study sponsor or research team.

Hannes Widing

CONTACT

[email protected]

0046703957374

Per Persson

CONTACT

[email protected]

Sponsors and collaborators

Lead sponsor

Vastra Gotaland Region

Other Gov

Collaborators

  • Göteborg University
  • Sahlgrenska University Hospital

Registry information

Official study title

The Impact of Low Versus High Positive End-Expiratory Pressure on Diaphragm Function, Ventilation Efficiency, and Lung Mechanics During Pressure Support Ventilation: A Randomized Interventional Crossover Study

Acronym: INFLATE-ICU

Important dates

Study start
2025
Primary completion
2027
Study completion
2027
First posted
Sep 23, 2025
Registry last updated
Sep 23, 2025

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

Related clinical trials

Published trials that share one or more normalized conditions with this study.