Effect PEEP on Diaphragm

The Effects of Positive End-expiratory Pressure on the Position, Length and Contractibility of the Diaphragm.

This study evaluates the effect of positive end-expiratory pressure on the position, length and function of the diaphragm. During the first part of the study, physiological measurements of the diaphragm will be performed while participants receive non-invasive ventilation at different PEEP levels. During the second part of the study, MRI measurements of the diaphragm will be performed during a change in PEEP level.

Study Overview

• Status: Completed
• Conditions: Diaphragm Disease
• Intervention / Treatment: Other: PEEP: 5 cmH2O; Other: PEEP: 10 cmH2O; Other: PEEP: 15 cmH2O

Detailed Description

In almost all mechanically ventilated patients, positive end-expiratory pressure (PEEP) is used. Its function is to prevent alveolar collapse and to maintain oxygenation. However, it has recently been found that PEEP may contribute to diaphragm weakness, which is an important problem in the intensive care unit (ICU). This study showed that mechanical ventilation with PEEP resulted in a caudal displacement of the diaphragm, since PEEP increases the end-expiratory volume. Furthermore, their study in rats showed that this displacement resulted in a reduced fiber length and sarcomere length on the short term.

After rats were ventilated with PEEP for 18 hours, it was found that adaptation of the diaphragm occurred; i.e. the number of sarcomeres were decreased. It is hypothesized that this adaptation may also occur in mechanically ventilated patients. This could lead to problems in weaning a patient off the ventilator, as PEEP is abruptly removed during a spontaneous breathing trial (SBT). This leads to a reduction in end-expiratory volume which would mean that the newly-adapted diaphragm fibers are being stretched. These stretched muscle fibers are not working at their optimal length of the force-length relation, thereby contributing to diaphragm weakness.

• Study Type: Interventional
• Enrollment (Actual): 22
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Netherlands
  • Noord-Holland
    • Amsterdam, Noord-Holland, Netherlands, 1081 HV
      • VU Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Signed informed consent
• Age ≥ 18 years

Exclusion Criteria:

• Symptoms relating to respiratory or cardiovascular disease
• History of pneumothorax or family history of primary pneumothorax
• Obesity (defined as BMI > 30kg/m²)
• Known pregnancy
• Contraindications for the placement of a nasogastric tube (upper airway/esophageal/gastric/mouth or face pathology (e.g. recent surgery, esophageal varices, diaphragmatic hernia), nasal bleeding within the last 2 weeks or use of anticoagulants)
• Contraindications for MRI (electrical/metallic implants, claustrophobia or history in metalworking)
• Subjects who are employed at the department of intensive care adults, directly involved in the study and/or family from staff of the ICU.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: PEEP level of 5 cmH2O; During second part of the study (MRI) Diaphragm position	Other: PEEP: 5 cmH2O; During second part of the study (MRI)
Active Comparator: PEEP level of 10 cmH2O; During second part of the study (MRI) Diaphragm position	Other: PEEP: 10 cmH2O; During second part of the study (MRI)
Active Comparator: PEEP level of 15 cmH2O; During second part of the study (MRI) Diaphragm position	Other: PEEP: 15 cmH2O; During second part of the study (MRI)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in diaphragm's position	Changes in the position of the diaphragm during different PEEP levels, as measured with both ultrasound and MRI	2 hours
Changes in diaphragm's shape and length	Changes of the diaphragm's shape and length during different PEEP levels, as measured with MRI	2 hours
Changes in diaphragm's efficiency	Changes in the neuro-mechanical efficiency of the diaphragm (ratio between pressure and electrical muscle activity) during different PEEP levels, as measured with a nasogastric catheter	2 hours
Change in twitch transdiaphragmatic pressures	Twitch transdiaphragmatic pressures during different PEEP levels, as measured with magnetic stimulation of the phrenic nerves.	2 hours

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Difference between MRI and ultrasound	The difference between diaphragm parameters obtained by ultrasound and parameters obtained by MRI	2 hours

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Expiratory abdominal muscle activity	Expiratory abdominal muscle activity during different levels of PEEP measured with surface EMG electrodes	2 hours
Flow	Flow during different levels of PEEP measured by the non-invasive ventilator	2 hours

Collaborators and Investigators

• Sponsor: Amsterdam UMC, location VUmc
• Investigators: Principal Investigator: Leo Heunks, MD, PhD, Amsterdam UMC, location VUmc

Study record dates

Study Major Dates

• Study Start (Actual): April 13, 2018
• Primary Completion (Actual): December 12, 2018
• Study Completion (Actual): May 1, 2019

Study Registration Dates

• First Submitted: April 17, 2018
• First Submitted That Met QC Criteria: May 16, 2018
• First Posted (Actual): May 29, 2018

Study Record Updates

• Last Update Posted (Actual): May 20, 2020
• Last Update Submitted That Met QC Criteria: May 19, 2020
• Last Verified: May 1, 2020

More Information

Terms related to this study

• Keywords: Diaphragm; PEEP
• Other Study ID Numbers: NL63905.029.17

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No