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

NCT07188038 | Not Yet Recruiting

• 1 other identifier: 2025-01286-01
• Study Type: interventional
• Target: 25
• Locations: 1 country
• Sites: 2

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.

Conditions

Respiratory Failure; ARDS (Acute Respiratory Distress Syndrome); Pneumonia; Respiratory Insufficiency

Keywords

Positive end-expiratory pressure; PEEP; pressure support ventilation; assisted breathing; Inspiratory effort; Inspiratory drive; Ventilation efficiency; Diaphragm

Outcome Measures

Primary Outcomes (7)

• Inspiratory effort

  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.

  Measured during 5 uninterrupted breaths 10 minutes after application of interventional PEEP level

• Inspiratory drive

  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.

  Measured during 5 uninterrupted breaths 10 minutes after application of interventional PEEP level

• Effort-to-drive ratio

  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).

  Calculated from the measures collected 10 minutes after application of interventional PEEP level

• Neuromechanical efficiency

  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).

  Calculated from the measures collected during the occlusion manoeuvre performed 10-15 minutes after application of interventional PEEP level

• Thickening fraction of the diaphragm (TFdi)

  Measured by ultrasound at the right hemidiaphragm. The thickening fraction of the diaphragm (TFdi) will be calculated as \[ (end-inspiratory diaphragm thickness - end-expiratory diaphragm thickness) / end-expiratory diaphragm thickness) \].

  Measured 10 minutes after application of interventional PEEP level

• Transpulmonary driving pressure

  Change in transpulmonary pressure ( airway pressure - esophageal pressure) from end-expiration to end-inspiration will be calculated using ventilator data and high-resolution manometry

  Measured during 5 breaths 10 minutes after application of interventional PEEP level

• Occlusion pressure

  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.

  The occlusion pressure will be measured during an occlusion manoeuvre performed 10-15 minutes after application of interventional PEEP level.

Secondary Outcomes (5)

• Airway driving pressure

  Measured during an inspiratory hold performed 10-15 minutes after application of interventional PEEP level

• Lung compliance

  Measured during an inspiratory hold performed 10 - 15 minutes after application of interventional PEEP level

• Thickening fraction of the expiratory abdominal muscles (TFabd)

  Measured 10 minutes after application of interventional PEEP level

• Oxygenation

  The blood gas will be collected 10 minutes after application of interventional PEEP level

• Respiratory system compliance

  Measured during an inspiratory hold manoeuvre performed 10-15 minutes after the application of interventional PEEP level.

Other Outcomes (10)

• Central venous oxygen saturation (ScvO2)

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

• Tidal volume

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

• Respiratory rate

  Measured 10 minutes after the application of interventional PEEP level.

Study Arms (3)

Low PEEP

EXPERIMENTAL

Low positive end-expiratory pressure (4 cmH2O)

Procedure: Low positive end-expiratory pressure

Medium PEEP

EXPERIMENTAL

Medium positive end-expiratory pressure (10 cmH2O)

Procedure: Medium positive end-expiratory pressure

High PEEP

EXPERIMENTAL

High positive end-expiratory pressure (16 cmH2O)

Procedure: High positive end-expiratory pressure

Interventions

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.

Low PEEP

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.

Medium PEEP

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.

High PEEP

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Vastra Gotaland Region: lead
• Sahlgrenska University Hospital: collaborator
• Göteborg University: collaborator

Study Sites (2)

Central intensivvårdsavdelning, Sahlgrenska University Hospital

Gothenburg, Västra Götaland County, 413 45, Sweden

Location

Thorax intensivvårdsavdelning, Område 6, Sahlgrenska University Hospital, Västra Götalandsregionen

Gothenburg, Västra Götaland County, 413 45, Sweden

Location

MeSH Terms

Conditions

Respiratory Insufficiency; Acute Lung Injury; Pneumonia

Condition Hierarchy (Ancestors)

Respiration Disorders; Respiratory Tract Diseases; Lung Injury; Lung Diseases; Respiratory Tract Infections; Infections

Study Officials

• Hannes Widing

  Anesthesia and intensive care medicine, Område 5, Sahlgrenska University hospital, Västra Götalandsregionen

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Hannes Widing

CONTACT

0046703957374; hannes.widing@vgregion.se

Per Persson

CONTACT

per.persson@gregion.se

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: SUPPORTIVE CARE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER GOV
• Responsible Party: SPONSOR

Model Details: Randomized interventional crossover study

Study Record Dates

• First Submitted: September 1, 2025
• First Posted: September 23, 2025
• Study Start: October 1, 2025
• Primary Completion (Estimated): July 31, 2027
• Study Completion (Estimated): December 31, 2027
• Last Updated: September 23, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will not share

Locations

SE (2)